Liquid-phase peptide support synthesis of peptides and peptidomimetics

Description

LIQUID-PHASE PEPTIDE SUPPORT SYNTHESIS OF PEPTIDES AND PEPTIDOMIMETICS Revelation Area

[001] The present disclosure relates to the synthesis of liquid-phase peptide scaffolding of peptides and peptidomimetics, pharmaceutical compositions and methods of treating conditions associated with GLP1R. Foundations of Revelation

[002] The difference between liquid-phase peptide support synthesis (LPPS) and solid-phase peptide synthesis (SPPS) is that while the latter is supported on a large solid polymer, the former is supported on well-defined molecules, and the difference between LPPS and CSPS is precipitation as an isolation in LPPS versus phase separation in CSPS. SPPS is a well-established and more common and favored method for preparing polypeptides (Jaradat D., “Thirteen Decades of Peptide Synthesis: Key Developments in Solid Phase Peptide Synthesis and Amide Bond Formation Utilized in Peptide Ligation,” Amino Acids 50(1):39-68 (2018)). However, its heterogeneity requires a large excess of molar equivalents of amino acid building blocks to ensure the completion of peptide chain elongation. On the other hand, CSPS requires fewer molar equivalents of building blocks, but is tedious and time-consuming in isolation and purification. It is challenging to generate a suitable chemistry associated with LPPS to eliminate the need for purification phases and reduce molar equivalents of building blocks, especially non-natural amino acids in peptidomimetic synthesis, which are problematic for scale-up and overall material consumption.

[003] Initial approaches using the well-known LPPS Tag (Tag1 in Figure 1) (Takahashi et al., “Novel Diphenylmethyl-Derived Amide Protecting Group for Efficient Liquid-Phase Peptide Synthesis: AJIPHASE,” Org Lett. 14(17):4514-4517 (2012); Petition 870260086043, dated 08 / 24 / 2026, page 7 / 389 2 / 328 Takahashi et al., “Novel Diphenylmethyl-Derived Amide Protecting Group for Efficient Liquid-Phase Peptide Synthesis: AJIPHASE,” Org Lett. 14(17):4514-4517 (2012)) to prepare a 10-mer peptidomimetic (M1) composed of five natural and five non-natural amino acid residues were unsuccessful. Peptide chain elongation only reached the 7th amino acid residue due to poor separation of tag carrier peptides (TCPs) from the reaction mixture.

[004] Consequently, there is a need in the art for new tag carriers with improved separation of the tag carrier peptides from the reaction mixture. In certain embodiments, the present disclosure meets the needs and offers further advantages.

[005] The preceding discussion is presented solely to provide a better understanding of the nature of the problems faced by the technique and should in no way be interpreted as an admission as to the state of the art, nor should the citation of any reference contained herein be interpreted as an admission that such reference constitutes “state of the art” for the present application. Summary of Revelation

[006] Several non-limiting aspects and modalities of disclosure are described below.

[007] In one aspect, the present disclosure provides a compound with a structure of Formula (I): Petition 870260086043, dated 08 / 24 / 2026, p. 8 / 389 3 / 328 where: men are, independently, an integer from 1 to 5, and (m+n)>3; R1 is a C1-5 alkyl; R2 is, independently in each occurrence, an optionally substituted C10-30 alkyl; and R3 is, independently in each occurrence, an optionally substituted C10-30 alkyl group, or a salt thereof.

[008] In some embodiments, R1 is methyl.

[009] In some embodiments, R2 is, independently, in each instance, an optionally substituted C18-26 alkyl and R3 is, independently, in each instance, an optionally substituted C18-26 alkyl. In some embodiments, each R2 is, independently, an optionally substituted C22 alkyl and each R3 is, independently, an optionally substituted C22 alkyl.

[010] In some embodiments, the compound has a structure of Formula (Ia): C22H45 C22H45 (Ia) or a salt thereof.

[011] In another aspect, the present disclosure provides a process for preparing a compound of Formula (I): Petition 870260086043, dated 08 / 24 / 2026, p. 9 / 389 4 / 328 in which: men are, independently, an integer from 1 to 5, and (m+n)>3; R1 is a C1-5 alkyl; R2 is, independently in each occurrence, an optionally substituted C10-30 alkyl; and R3 is, independently in each occurrence, an optionally substituted C10-30 alkyl group, or a salt thereof. This process includes: (a) provide a compound of Formula (II) with the structure: in which PG is a suitable protecting group; and (b) form the compound of Formula (I) from the compound of Formula (II).

[012] In some embodiments, PG is selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc). Petition 870260086043, dated 08 / 24 / 2026, p. 10 / 389 5 / 328

[013] In some forms, the compound of Formula (II) has the structure of Formula (IIa): (IIa)

[014] In some embodiments, step (b) of forming the compound of Formula (I) comprises the reaction of the compound of Formula (II) with a protective group removing agent to produce the compound of Formula (I). In some embodiments, the protective group removing agent is selected from the group consisting of Pd(PPh)3, PhSiH3, H2, piperidine and trifluoroacetic acid (TFA).

[015] In some embodiments, the process for preparing a compound of Formula (I) also includes a step of providing a compound of Formula (III) with the structure: R1O in which PG1 is an adequate protective group; PG2 is a suitable protecting group; and form the compound of Formula (II) from the compound of Petition 870260086043, dated 08 / 24 / 2026, page 11 / 389 6 / 328 Formula (III) before step (a).

[016] In some embodiments, PG1 is selected independently from the group consisting of tert-butyldimethylsilyl (TBS), trimethylsilyl (TMS), triethylsilyl (TES), tert-butyldiphenylsilyl (TBDPS) and triisopropylsilyl (TIPS).

[017] In some embodiments, PG2 is selected independently from the group consisting of tert-butyldimethylsilyl (TBS), trimethylsilyl (TMS), triethylsilyl (TES), tert-butyldiphenylsilyl (TBDPS) and triisopropylsilyl (TIPS).

[018] In some modalities, each PG1 and each PG2 are equal. In some game modes, PG1 and PG2 are different from each other.

[019] In some forms, the Formula (III) compound has the Formula (IIIa) structure:

[020] In some embodiments, the compound formation step of Formula (II) before step (a) comprises: react the compound of Formula (III) with a protecting group removing agent to obtain an unprotected intermediate; react the said intermediate with at least one compound of Formula (IV): R-LG (IV), where R is an optionally substituted C10-30 alkyl; and LG is a suitable output group; Petition 870260086043, dated 08 / 24 / 2026, p. 12 / 389 7 / 328 to produce the compound of Formula (II).

[021] In some embodiments, LG is selected from a group consisting of halogen, OTf, OMs and OTs.

[022] In some embodiments, the protecting group removal agent is selected from the group consisting of tetrabutylammonium fluoride (TBAF), NH4F, SiF4, AcOH, HCl, LiAlH4 and K2CO3.

[023] In some embodiments, the process for preparing a compound of Formula (I) additionally comprises a step of: provide a compound of Formula (V) with the structure: form the compound of Formula (III) from the compound of Formula (V).

[024] In some embodiments, the compound formation step of Formula (III) comprises: react the compound of Formula (V) with a compound of Formula (VIa) or Formula (VIb): PG-X (VIa) or PG2O (VIb), where X is Cl or Br; to produce the compound of Formula (III).

[025] In some embodiments, the compound of Formula (VIa) or Formula (VIb) is selected from the group consisting of AllocCl, Alloc2O, Cbz2O, CbzCl, FmocCl and Boc2O.

[026] In some embodiments, the process for preparing a compound of Formula (I) additionally comprises: Petition 870260086043, dated 08 / 24 / 2026, p. 13 / 389 8 / 328 provide a compound of Formula (VII) with the structure: (VII); where PG3 is a suitable protecting group; and form the compound of Formula (V) from the compound of Formula (VII).

[027] In some embodiments, PG3 is selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

[028] In some forms, the compound of Formula (VII) has the following structure: OTBS (VIIa) .

[029] In some embodiments, the said step of forming the compound of Formula (V) comprises the reaction of the compound of Formula (VII) with a protecting group removing agent to produce the compound of Formula (V). In some embodiments, the protecting group removing agent is selected from the group consisting of Pd(PPh)3, PhSiH3, H2, piperidine and trifluoroacetic acid (TFA).

[030] In some modalities, the process for preparing Petition 870260086043, dated 08 / 24 / 2026, p. 14 / 389 9 / 328 a compound of Formula (I) further comprises: provide a compound of Formula (VIII) with the structure: to form the compound of Formula (VII) from the compound of Formula (VIII).

[031] In some embodiments, the process of forming the compound of Formula (VII) may involve the reaction of the compound of Formula (VIII) with a compound of Formula (IX) with the structure: PG3 (IX) to produce the compound of Formula (VII).

[032] In some forms, the compound of Formula (VIII) has the following structure: (VIIIa).

[033] In some forms, the compound of Formula (IX) has the following structure: (IXa).

[034] In some modalities, the process for preparing Petition 870260086043, dated 08 / 24 / 2026, p. 15 / 389 10 / 328 a compound of Formula (I) further comprises: providing a compound of Formula (X) with the structure: pg4-n |j ^w.(0-PG2)n (X), where PG4 is a suitable protecting group; and form the compound of Formula (VIII) from the compound of Formula (X).

[035] In some embodiments, PG4 is selected from the group consisting of allyl, allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

[036] In some forms, the compound of Formula (X) has the following structure: TBSO OTBS TBSO )= / x 4 OTBS TBSO— / \\ )= / N—' TBSO r.—f( (Xa) .

[037] In some embodiments, the compound formation step of Formula (VIII) comprises the reaction of the compound of Formula (X) with a protecting group removing agent. In some embodiments, the protecting group removing agent is selected from the group consisting of Pd / K2CO3, 1,3-dimethylbarbituric acid / Pd(PPh3)4, Pd(PPh)3, PhSiH3, H2, piperidine and trifluoroacetic acid (TFA).

[038] In some embodiments, the process for preparing a compound of Formula (I) further comprises: providing a compound of Formula (XI) with the structure: Petition 870260086043, dated 08 / 24 / 2026, p. 16 / 389 11 / 328 O (O-PG1)m (XI); form the compound of Formula (X) from the compound of Formula (XI).

[039] In one embodiment, the compound of Formula (XI) has the following structure: OTBS TBSO^Jx. TBSO (XIa).

[040] In some embodiments, the process of forming the compound of Formula (X) comprises: react the compound of Formula (XI) with a compound of Formula (XII): ^^NH2 (XII), or a salt thereof, to produce the compound of Formula (X).

[041] In some embodiments, the process for preparing a compound of Formula (I) additionally comprises: provide a compound of Formula (XIII) with the structure: (O-PG1)m OH (XIII); and form the compound of Formula (XI) from the compound of Formula (XIII).

[042] In some forms, the compound of Formula (XIII) has the following structure: OTBS TBSO. / L JL J. / OH TBSO (XIIIa).

[043] In some embodiments, the process for forming the compound of Formula (XI) comprises the reaction of the compound of Petition 870260086043, dated 08 / 24 / 2026, p. 17 / 389 12 / 328 Formula (XIII) with an oxidizing agent to produce the compound of Formula (XI). In some embodiments, the oxidizing agent may be selected from the group consisting of pyridinium chlorochromate (PCC), pyridinium dichromate (PDC), silver carbonate (Ag2CO3), tetra-n-propylammonium perruthenate (TPAP), and Dess-Martin periodinane (DMP).

[044] In some embodiments, the process for preparing a compound of Formula (I) additionally comprises: provide a compound of Formula (XIV) with the structure: 0(XIV), where Y is -OC1-6 alkyl; and form the compound of Formula (XIII) from the compound of Formula (XIV).

[045] In one embodiment, the compound of Formula (XIV) has the following structure: OTBS TBSO^X TBSO ψ0(XIVa).

[046] In some embodiments, the process of forming the compound of Formula (XIII) comprises the reaction of the compound of Formula (XIV) with a reducing agent. In some embodiments, the reducing agent is selected from the group consisting of LiAlH4, DIBALH and LiBH4.

[047] In some embodiments, the process for preparing a compound of Formula (I) additionally comprises: provide a compound of Formula (XV) with the structure: The (XV) ; and Petition 870260086043, dated 08 / 24 / 2026, p. 18 / 389 13 / 328 form the compound of Formula (XIV) from the compound of Formula (XV).

[048] In some forms, the compound Formula (XV) has the following structure: (XVa).

[049] In some embodiments, the process of forming the compound of Formula (XIV) comprises the reaction of the compound of Formula (XV) with a protecting group introducing agent to produce the compound of Formula (XIV). In some embodiments, the protecting group introducing agent is selected from the group consisting of TBSCl, TBSOTf, TMSCl, TMSOTf, TESCl, TESOTf, TBDPSCl, TBDPSOTf, TIPSCl and TIPSOTf.

[050] In another aspect, the present disclosure provides a product prepared in accordance with any of the methods described in the present disclosure.

[051] In some embodiments, the product is a compound of Formula (I): in which: men are, independently, an integer from 1 to 5, and (m+n)>3; R1 is a C1-5 alkyl; R2 is, independently in each occurrence, a C10-30 alkyl Petition 870260086043, dated 08 / 24 / 2026, p. 19 / 389 14 / 328 optionally replaced; and R3 is, independently in each occurrence, an optionally substituted C10-30 alkyl group, or a salt thereof.

[052] In one embodiment, the product is a compound of Formula (Ia): or a salt of the same. (Ia),

[053] In a further aspect, the present disclosure provides a method of using a compound of Formula (I): in which: men are, independently, an integer from 1 to 5, and (m+n)>3; R1 is a C1-5 alkyl; R2 is, regardless of whether it is optionally replaced; and R3 is, independently in each occurrence, a C10-30 alkyl group, optionally substituted. Petition 870260086043, dated 08 / 24 / 2026, page 20 / 389 15 / 328 or a salt thereof, to produce a peptide or a peptidomimetic.

[054] In some forms, the compound of Formula (I) used as a carrier or a tag to produce a peptide or a peptidomimetic.

[055] In one embodiment, the peptidomimetic is a compound of Formula: h2n or a salt of it.

[056] In one embodiment, the peptidomimetic is a compound of Formula: / NH N Λ HN-N OH THE NH NH2 o the OO N=N o H 5 N.A. NH2 or a salt of it.

[057] In another aspect, the present disclosure provides a compound manufactured using a compound of Formula (I): Petition 870260086043, dated 08 / 24 / 2026, p. 21 / 389 16 / 328 in which: men are, independently, an integer from 1 to 5, and (m+n)>3; R1 is C1-5 alkyl; R2 is selected independently at each occurrence of a C10-30 optionally substituted alkyl; and R3 is selected independently at each occurrence of a Optionally substituted C10-30 alkyl, or a salt thereof.

[058] In one form, the compound has a formula: a salt of the same.

[059] In one form, the compound has a formula: Petition 870260086043, dated 08 / 24 / 2026, p. 22 / 389 17 / 328 a salt of the same.

[060] In another aspect, a pharmaceutical composition comprising the peptidomimetic or the compound of any of the embodiments described herein is provided herein.

[061] In a further aspect, a pharmaceutical dosage form comprising the peptidomimetic or compound of any of the embodiments described herein is provided herein.

[062] In another aspect, a method is provided here for selectively targeting GLP1R on the surface of a cell with the compound or peprodomimetic of any of the embodiments described herein. In some embodiments, the cell is a mammalian cell. In some embodiments, the cell is a human cell.

[063] In another aspect, a method is provided here for increasing the activity of GLP1R in an individual who needs it comprising administering to the individual an effective amount of the peptidomimetic or compound of any of the embodiments described herein, of the composition described herein or of the dosage form described herein.

[064] In another aspect, a method is provided here for reducing blood glucose levels in an individual who needs it, comprising administering to the individual an effective amount of the peptidomimetic or compound of any of the embodiments described herein, of the composition described herein or of the dosage form described herein.

[065] In a further aspect, a method is provided here for reducing body weight in an individual who needs it comprising administering to the individual an effective amount of the peptidomimetic or compound of any of the embodiments described herein, of the composition described herein or of the dosage form described herein.

[066] In another aspect, a method is provided here for treating a condition associated with GLP1R in an individual in need comprising administering to the individual a Petition 870260086043, dated 08 / 24 / 2026, p. 23 / 389 18 / 328 effective amount of the peptidomimetic or compound of any of the embodiments described herein, of the composition described herein, or of the pharmaceutical form described herein. In some embodiments, the condition associated with GLP1R is type II diabetes, obesity, liver disease, coronary artery disease, or kidney disease. In some embodiments, the condition associated with GLP1R is type II diabetes and / or obesity. In some embodiments, the peptidomimetic or compound of any of the embodiments described herein, the composition described herein, or the pharmaceutical form described herein is administered subcutaneously, intravenously, intradermally, intraperitoneally, or intramuscularly.

[067] In another aspect, a method is provided here for producing a peptide or a peptidomimetic, the method comprising the steps of: (a) provide a compound of Formula (I): in which: men are, independently, an integer from 1 to 5, and (m+n)>3; R1 is C1-5 alkyl; R2 is selected independently at each occurrence of a optionally substituted C10-30 alkyl; and R3 is selected independently at each occurrence of a C10-30 alkyl optionally substituted, or a salt thereof; (b) provide a first amino acid (AA1); and Petition 870260086043, dated 08 / 24 / 2026, p. 24 / 389 19 / 328 (c) attach the first amino acid (AA1) to the compound of Formula (I) to form a peptide bond between the first amino acid (AA1) and the compound of Formula (I).

[068] In some embodiments, the first amino acid (AA1) contains a protected amino group.

[069] In some forms, the first amino acid (AA1) is the

[070] In some embodiments, the method of producing a peptide or a peptidomimetic may include a step of activating the chemical groups on the first amino acid (AA1) to prepare the first amino acid (AA1) for coupling with the compound of Formula (I) before step (c).

[071] In some embodiments, the method of producing a peptide or a peptidomimetic may include the steps of: (d) remove the protecting group from the first amino acid (AA1); (e) provide a second amino acid (AA2); and (f) couple the second amino acid (AA2) to the first amino acid (I-AA1) to form a peptide bond between the second amino acid (AA2) and the first amino acid (I-AA1-AA2).

[072] In some forms, the second amino acid (AA2) is

[073] In some embodiments, the method of producing a peptide or a peptidomimetic may include the steps of: (g) remove the protecting group from the second amino acid (AA2); (h) provide a third amino acid (AA3); and (i) couple the third amino acid (AA3) to the second amino acid to form a peptide bond between the third amino acid (AA3) and the second amino acid (I-AA1-AA2-AA3). Petition 870260086043, dated 08 / 24 / 2026, p. 25 / 389 20 / 328

[074] In some forms, the third amino acid (AA3) is NHFmoc

[075] In some embodiments, the method of producing a peptide or peptidomimetic may include the steps of: (j) remove the protecting group from the third amino acid (AA3); (k) provide a fourth amino acid (AA4); and (l) couple the fourth amino acid (AA4) to the third amino acid to form a peptide bond between the fourth amino acid (AA4) and the third amino acid (I-AA1-AA2-AA3-AA4).

[076] In some forms, the fourth amino acid (AA4) is NHFmoc or NHFmoc

[077] In some embodiments, the method of producing a peptide or peptidomimetic may include the steps of: (m) remove the protecting group from the fourth amino acid (AA4); (n) provide a fifth amino acid (AA5); and (o) couple the fifth amino acid (AA5) to the fourth amino acid to form a peptide bond between the fifth amino acid (AA5) and the fourth amino acid (I-AA1-AA2-AA3-AA4-AA5).

[078] In some forms, the fifth amino acid (AA5) is NHFmoc or NHFmoc

[079] In some embodiments, the method of producing a peptide or peptidomimetic may include the steps of: (p) remove the protecting group from the fifth amino acid (AA5); (q) provide a sixth amino acid (AA6); and (r) couple the sixth amino acid (AA6) to the fifth amino acid to form a peptide bond between the sixth amino acid (AA6) and the fifth amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6).

[080] In some forms, the sixth amino acid (AA6) is Petition 870260086043, dated 08 / 24 / 2026, p. 26 / 389 21 / 328

[081] In some embodiments, the method of producing a peptide or peptidomimetic may include the steps of: (s) remove the protecting group from the sixth amino acid (AA6); (t) provide a seventh amino acid (AA7); and (u) couple the seventh amino acid (AA6) to the sixth amino acid to form a peptide bond between the seventh amino acid (AA7) and the sixth amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6-AA7).

[082] In some forms, the seventh amino acid (AA7) is NHFmoc or OH NHFmoc

[083] In some embodiments, the method of producing a peptide or a peptidomimetic may include the steps of: (v) remove the protecting group from the seventh amino acid (AA7); (w) provide an eighth amino acid (AA8); and (x) couple the eighth amino acid (AA8) to the seventh amino acid to form a peptide bond between the eighth amino acid (AA8) and the seventh amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6-AA7-AA8).

[084] In some forms, the eighth amino acid (AA8) is THE FmocHN. , OH .

[085] In some embodiments, the method of producing a peptide or peptidomimetic may include the steps of: (y) remove the protecting group from the eighth amino acid (AA8); (z) provide a ninth amino acid (AA9); and (aa) couple the ninth amino acid (AA9) to the eighth amino acid to form a peptide bond between the ninth amino acid (AA9) and the eighth amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6-AA7-AA8-AA9).

[086] In some forms, the ninth amino acid (AA9) is Petition 870260086043, dated 08 / 24 / 2026, p. 27 / 389 22 / 328 Nn Ntii-moc ou OH NHFmoc

[087] In some embodiments, the method of producing a peptide or peptidomimetic may include the steps of: (bb) remove the protecting group from the ninth amino acid (AA9); (cc) provide a tenth amino acid (AA10); and (dd) couple the tenth amino acid (AA10) to the ninth amino acid to form a peptide bond between the tenth amino acid (AA10) and the ninth amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6-AA7-AA8-AA9-AA10).

[088] In one embodiment, the tenth amino acid (AA10) is .Trt y~NOO .

[089] In some embodiments, the method of producing a peptide or a peptidomimetic may include the steps of: repeating the steps of (i) removing the amino acid protecting group (AAn); (ii) provide a successor amino acid (AAn+1); and (iii) couple the successor amino acid (AAn+1) to the amino acid (AAn) to form a peptide bond between the successor amino acid (AAn+1) and the amino acid (AAn), wherein said repetition may be carried out from 1 to 100 times.

[090] In some embodiments, the method of producing a peptide or peptidomimetic may include the steps of: (ee) remove the protecting group from the tenth amino acid (AA10); (ff) provide a compound of Formula (B): BocHN where x is an integer from 1 to 15; and (gg) couple the compound of Formula (B) to one of the amino acids in the peptide or peptidomimetic to form a triazole ring. Petition 870260086043, dated 08 / 24 / 2026, p. 28 / 389 23 / 328

[091] In some forms, the compound of Formula (B) has the following Formula:

[092] In some embodiments, the method of producing a peptide or a peptidomimetic according to any of the above embodiments further comprises: (hh) cleave the peptide bond between the first amino acid (AA1) and the compound of Formula (I) to obtain the peptide or peptidomimetic.

[093] In some embodiments, each of the first amino acid (AA1), second amino acid (AA2), third amino acid (AA3), fourth amino acid (AA4), fifth amino acid (AA5), sixth amino acid (AA6), seventh amino acid (AA7), eighth amino acid (AA8), ninth amino acid (AA9), tenth amino acid (AA10) and successor amino acid (AAn+i) can be selected independently of the group consisting of Petition 870260086043, dated 08 / 24 / 2026, p. 29 / 389 24 / 328 in which PG5 is a suitable protecting group. In some embodiments, PG5 is selected independently in each occurrence of the group consisting of triphenylmethyl (Trt), allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc), and 9-fluorenylmethoxycarbonyl (Fmoc).

[094] In some embodiments, each of the first amino acid (AA1), second amino acid (AA2), third amino acid (AA3), fourth amino acid (AA4), fifth amino acid (AA5), sixth amino acid (AA6), seventh amino acid (AA7), eighth amino acid (AA8), ninth amino acid (AA9), tenth amino acid (AA10), and successor amino acid (AAn+1) can be selected independently of the group that NHFmoc Petition 870260086043, dated 08 / 24 / 2026, p. 30 / 389 25 / 328

[095] In one embodiment, the peptidomimetic has a Formula: a salt of the same. Peptidomimetics have a formula:

[096] In one modality, or a salt of it.

[097] In another aspect, a compound with a structure of Formula (AI) is provided here: in which: Petition 870260086043, dated 08 / 24 / 2026, p. 31 / 389 26 / 328 men are, independently, a whole number from 0 to 5; R1a is C1-5 alkyl; R2a is, independently in each occurrence, an optionally substituted C10-30 alkyl; and R3a is, independently in each occurrence, an optionally substituted C10-30 alkyl, or a salt thereof.

[098] In some embodiments, R1a is methyl.

[099] In some embodiments, R2a is, independently, in each instance, an optionally substituted C18-26 alkyl, and R3a is, independently, in each instance, an optionally substituted C18-26 alkyl. In some embodiments, each R2a is, independently, an optionally substituted C22 alkyl and each R3a is, independently, an optionally substituted C22 alkyl.

[100] In another aspect, a compound with a structure of Formula (BI) is provided here: (BI), where: m is an integer from 1 to 5; R1bé C1-5 alkyl; and R2bé, independently in each occurrence, is an optionally substituted C10-30 alkyl; or a salt of it.

[101] In some embodiments, R1bé methyl.

[102] In some embodiments, R2bé independently, in each instance, an optionally substituted C18-26 alkyl. In some embodiments, each R2bé independently, an optionally substituted C22 alkyl. Petition 870260086043, dated 08 / 24 / 2026, p. 32 / 389 27 / 328

[103] In another aspect, a compound with a structure of Formula (CI) is provided here: (CI), where: men are, independently, an integer from 1 to 5, and (m+n)>3; R2cé, independently in each occurrence, is an optionally substituted C10-30 alkyl; and R3cé, independently in each occurrence, is an optionally substituted C10-30 alkyl, or a salt thereof.

[104] In some embodiments, R2 is, independently, in each instance, an optionally substituted C18-26 alkyl, and R3 is, independently, in each instance, an optionally substituted C18-26 alkyl. In some embodiments, each R2 is, independently, an optionally substituted C22 alkyl and each R3 is, independently, an optionally substituted C22 alkyl.

[105] In another aspect, a method is given here for preparing a compound of Formula (DI): in which: k is an integer from 1 to 15; q is an integer from 0 to 10; R1dé C1-6 alkyl; Petition 870260086043, dated 08 / 24 / 2026, p. 33 / 389 28 / 328 PG6 is a suitable protective group; and PG7 is a suitable protective group, or a salt thereof. This method includes: (a) provide a compound of Formula (DII) with the structure: (b) to form the compound of Formula (DI) from the compound of Formula (DII).

[106] In some embodiments, PG6 is selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

[107] In some embodiments, PG7 can be selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

[108] In some forms, the Formula (DI) compound has the structure of Formula (DIa) or Formula (DIb):

[109] In some forms, the Formula (DII) compound has Petition 870260086043, dated 08 / 24 / 2026, p. 34 / 389 29 / 328 the structure of Formula (DIIa) or Formula (DIIb):

[110] In some embodiments, step (b) of forming the compound of Formula (DI) comprises: react the compound of Formula (DII) with a compound of Formula (DIII): (DIII), to produce the compound of Formula (II).

[111] In one embodiment, the compound of Formula (DIII) has the structure of Formula (DIIIa): (DIIIa)

[112] In some embodiments, the process for preparing a Formula (DI) compound may include the step of: provide a compound of Formula (DIV) with the structure: (DIV) or a salt thereof; and Petition 870260086043, dated 08 / 24 / 2026, p. 35 / 389 30 / 328 form the compound of Formula (DII) from the compound of Formula (DIV) before step (a).

[113] In some forms, the Formula (DIV) compound has the structure of Formula (DIVa) or Formula (DIVb):

[114] In some embodiments, the compound formation step of Formula (DII) comprises: react the compound of Formula (DIV) with a compound of Formula (DVa) or Formula (DVb): PG6-X (DVa) or PG62O (DVb), where X is OSu, OTf, Cl, or Br; to produce the compound of Formula (DII).

[115] In some embodiments, the Formula (DVa) or Formula (DVb) compound is selected from the group consisting of AllocCl, Alloc2O, Cbz2O, CbzCl, FmocCl, FmocOSu and Boc2O.

[116] In some embodiments, the process for preparing a Formula (DI) compound may include the step of: provide a Formula (DVI) compound with the following structure: Petition 870260086043, dated 08 / 24 / 2026, p. 36 / 389 31 / 328 in which PG8 is a suitable protecting group; and form the compound of Formula (DIV) from the compound of Formula (DVI).

[117] In some embodiments, the Formula (DIV) compound formation step comprises reacting the Formula (DVI) compound with a protecting group removing agent to produce the Formula (DIV) compound. In some embodiments, the protecting group removing agent may be selected from the group consisting of Pd(PPh)3, PhSiH3, H2, HCl, piperidine and trifluoroacetic acid (TFA).

[118] In some forms, the Formula (DVI) compound has the structure of Formula (DVIa) or Formula (DVIb):

[119] In some embodiments, the process for preparing a Formula (DI) compound may include the step of: provide a compound of Formula (DVII) with the structure: Petition 870260086043, dated 08 / 24 / 2026, p. 37 / 389 32 / 328 PG8Ο HN,, A < OMe zazU n3 / JI A R1 dv / CI (DVII); and form the compound of Formula (DVI) from the compound of Formula (DVII).

[120] In some embodiments, the compound formation step of Formula (DVI) comprises the reaction of compound Formula (DVII) with a base to produce compound Formula (DVI). In some embodiments, the base is selected from the group consisting of LiOH, NaOH, and KOH.

[121] In some forms, the compound of Formula (DVII) has the structure of Formula (DVIIa) or Formula (DVIIb):

[122] In some embodiments, the process for preparing a Formula (DI) compound may include the step of: provide a compound of Formula (DVIII) with the structure: Petition 870260086043, dated 08 / 24 / 2026, pp. 38 / 389 33 / 328 in which LG' is a suitable life group; and form the compound of Formula (DVII) from the compound of Formula (DVIII).

[123] In some embodiments, the compound formation step of Formula (DVII) comprises the reaction of the compound of Formula (DVIII) with an azide group-introducing agent to produce the compound of Formula (DVII). In some embodiments, the azide group-introducing agent is selected from the group consisting of NaN3, TMSN3, (PhO)2P(O)N3, Zn(N3)2*2Py and n-Bu4NN3.

[124] In some embodiments, LG' is selected from the group consisting of halogen, OTf, OMs and OTs.

[125] In some embodiments, the compound of Formula (DVIII) has the structure of Formula (DVIIIa) or Formula (DVIIIb):

[126] In some embodiments, the process for preparing a Formula (DI) compound may include the step of: Petition 870260086043, dated 08 / 24 / 2026, pp. 39 / 389 34 / 328 provide a compound of Formula (DIX) with the structure: in which (DIX), LG'' is a suitable life group; and form the compound of Formula (DVIII) from the compound of Formula (DIX).

[127] In some embodiments, LG'' is selected from the group consisting of halogen, OTf, OMs and OTs.

[128] In some embodiments, the compound formation step of Formula (DVIII) comprises: react the compound of Formula (DIX) with a compound of Formula PG8 is a suitable protective group; to produce the compound of Formula (DVII).

[129] In some embodiments, PG8 can be selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc). In some embodiments, PG8 is tert-butyloxycarbonyl (Boc).

[130] In some forms, the Formula (DIX) compound has the structure of Formula (DIXa): Br ov v(DIXa).

[131] In some modalities, the Formula (DX) compound has Petition 870260086043, dated 08 / 24 / 2026, p. 40 / 389 35 / 328 Formula structure (DXa): Boc (DXa).

[132] In some embodiments, the process for preparing a Formula (DI) compound may include the steps of: provide a compound with the formula (DXI) and the structure: LG LG R2d(DXI) where R2dé C1-6 alkylene; and form the compound of Formula (DIX) from the compound of Formula (DXI).

[133] In some embodiments, the compound formation step of Formula (DIX) comprises the reaction of the compound of Formula (DXI) with a reducing agent to produce the compound of Formula (DIX). In some embodiments, the reducing agent is selected from the group consisting of H2, NH4HCO2, NABH(OAc)3 and LiAlH4.

[134] In some forms, the Formula (DXI) compound has the Formula (DXIa) structure: (DXIa).

[135] In some embodiments, the process for preparing a Formula (DI) compound may include the steps of: provide a compound of Formula (DXII) with the structure: LG LG O (DXII), and form the compound of Formula (DXI) from the compound of Petition 870260086043, dated 08 / 24 / 2026, p. 41 / 389 36 / 328 Formula (DXII).

[136] In some embodiments, the compound formation step of Formula (DXI) comprises: react the compound of Formula (DXII) with a compound of Formula (DXIII): PPh3*C1-6alkyl-Hal (DXIII), where Hal is halogen, to produce the compound of Formula (DXI).

[137] In some forms, the compound of Formula (DXII) has the structure of Formula (DXIIa): O (DXIIa).

[138] In some embodiments, the compound of Formula (DXIII) has the structure of Formula (DXIIIa): PPh3*MeBr (DXIIIa).

[139] In some embodiments, the process for preparing a Formula (DI) compound may include the steps of: provide a compound of Formula (DXIV) with the structure: The (DXIV) compound, and form the compound of Formula (DXII) from the compound of Formula (DXIV).

[140] In some embodiments, the compound formation step of Formula (DXII) comprises: react the compound of Formula (DXIV) with a compound of Formula (DXV): LGUV( (DXV), where LG is a suitable social group. Petition 870260086043, dated 08 / 24 / 2026, p. 42 / 389 37 / 328 to produce the compound of Formula (DXII).

[141] In some embodiments, LG' is selected from the group consisting of halogen, OTf, OMs and OTs.

[142] In some embodiments, the compound of Formula (DXIV) has the structure of Formula (DXIVa): The (DXIVa).

[143] In some embodiments, the process for preparing a compound of Formula (DI) may include the steps of: providing a compound of Formula (DXVI) with the structure: PG8O । II HN,, X ·< OMe jQT LG* (DXVI), and where LG* is a suitable cohabiting group, form the compound of Formula (DX) from the compound of Formula (DXVI).

[144] In some embodiments, LG* is selected from the group consisting of halogen, OTf, OMs and OTs.

[145] In some forms, the compound formation step of Formula (DX) comprises: react the compound of Formula (DXVI) with a compound of Formula (DXVII): (DXVII), to produce the compound of Formula (DX).

[146] In some forms, the Formula (DXVI) compound has the Formula (DXVIc) structure: Petition 870260086043, dated 08 / 24 / 2026, p. 43 / 389 38 / 328 Boc O OTf (DXVIc).

[147] In some embodiments, the process for preparing a Formula (DI) compound may include the steps of: provide a compound of Formula (DXVIII) with the structure: PG8O OH (DXVIII), and form the compound of Formula (DXVI) from the compound of Formula (DXVIII).

[148] In some forms, the compound formation step of Formula (DXVI) comprises: react the compound of Formula (DXVIII) with a compound of Formula (DXIXa) or Formula (DXIXb): LG*-X (DXIXa) or LG*2O (DXIXb), where X is OSu, Cl, or Br; to produce the compound of Formula (DXVI).

[149] In some embodiments, the compound of Formula (DXIXa) or Formula (DXIXb) is selected from the group consisting of TfCl, Tf2O, MsCl and Ms2O.

[150] In a further aspect, a method for preparing a compound of Formula (DII) is provided here: Petition 870260086043, dated 08 / 24 / 2026, p. 44 / 389 39 / 328 where: q is an integer from 0 to 10; R1dé C1-6 alkyl; e PG6 is a suitable protecting group, or a salt thereof, the said process comprising: (a) provide a compound of Formula (DXXI) with the structure: (DXXI) or a salt thereof, (b) form the compound of Formula (DII) from the compound of Formula (DXXI).

[151] In some embodiments, PG6 is selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

[152] In some forms, the compound of Formula (DXXI) is O NHFmoc treated with compound 1.

[153] In some embodiments, the compound of Formula (DXXI) is treated with a catalyst. In some embodiments, the catalyst is Pd(dppf)Cl2-DCM.

[154] In some embodiments, the compound of Formula (DXXI) is treated with a base. In some embodiments, the base is K2CO3.

[155] In some embodiments, the preparation is carried out in a solvent mixture composed of H2O / iPrOH.

[156] In some embodiments, the compound of Formula (DII) has the structure of Formula (DIIa) or Formula (DIIb): Petition 870260086043, dated 08 / 24 / 2026, p. 45 / 389 40 / 328

[157] In some forms, the Formula (DXXI) compound is formed by exposure

[158] In some embodiments, the compound of Formula (DXXI) is formed in the presence of PPh

[159] In some forms, the Formula (DXXI) compound is formed in the presence of DIAD.

[160] In some embodiments, the compound of Formula (DXXI) is formed in the presence of 4Å molecular sieves.

[161] In some embodiments, the compound of Formula (DXXI) is formed in an organic solvent. In some embodiments, the organic solvent is THF.

[162] In some modalities, exhibition a PBin . formed by Petition 870260086043, dated 08 / 24 / 2026, page 46 / 389 41 / 328

[163] In some forms, presence of Pd(OAc)2. trained in

[164] In some forms, formed in the presence of PCy3.

[165] In some modalities, presence of KOAc. trained in

[166] In some forms, formed in the presence of dioxane.

[167] In some forms, formed at a high temperature over a period of time.

[168] In some forms, Br R1dé formed by the exhibition Bu4N+Br3-.

[169] In some forms, formed in an organic solvent. In some embodiments, the organic solvent is a mixture of DCM and methanol. Petition 870260086043, dated 08 / 24 / 2026, p. 47 / 389 42 / 328

[170] In a further aspect, a method is given here for preparing a compound of Formula (DII): q is an integer from 0 to 10; R1dé C1-6 alkyl; e PG6 is a suitable protecting group, or a salt thereof, the said process comprising: (a) provide a compound of Formula (DIV) with the structure: (DIV) or a salt thereof, (b) form the compound of Formula (DII) from the compound of Formula (DIV).

[171] In some embodiments, PG6 can be selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

[172] In some embodiments, the compound of Formula (DII) has the structure of Formula (DIIa) or Formula (DIIb): Petition 870260086043, dated 08 / 24 / 2026, p. 48 / 389 43 / 328

[173] In some forms, the Formula (DIV) compound has the structure of Formula (DIVa) or Formula (DIVb):

[174] In some embodiments, the process of forming the compound of Formula (DII) comprises: react the compound of Formula (DIV) with a compound of Formula (DVa) or Formula (DVb): PG6-X (DVa) or PG62O (DVb), where X is OSu, OTf, Cl, or Br; to produce the compound of Formula (DII). Petition 870260086043, dated 08 / 24 / 2026, p. 49 / 389 44 / 328

[175] In some embodiments, the compound of Formula (DVa) or Formula (DVb) is selected from the group consisting of AllocCl, Alloc2O, Cbz2O, CbzCl, FmocCl, FmocOSu and Boc2O.

[176] In some embodiments, the process for preparing a Formula (DII) compound may include the steps of: provide a compound of Formula (DXVI) with the structure: OCi-6 alkyl (DXVI) where PG8 is a suitable protecting group; and form the compound of Formula (DIV) from the compound of Formula (DXVI).

[177] In some embodiments, PG8 is selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

[178] In some embodiments, the compound formation step of Formula (DIV) comprises reacting the compound of Formula (DXVI) with a protecting group removing agent to produce the compound of Formula (DIV). In some embodiments, the protecting group removing agent is selected from the group consisting of HCl, Pd(PPh)3, PhSiH3, H2, piperidine and trifluoroacetic acid (TFA).

[179] In some forms, the Formula (DXVI) compound has the structure of Formula (DXVIa) or Formula (DXVIb): Petition 870260086043, dated 08 / 24 / 2026, p. 50 / 389 45 / 328 (DXVIb).

[180] In some embodiments, the process for preparing a Formula (DII) compound may include the steps of: provide a compound of Formula (DXVII) with the structure: PG8O .1... II OCi-6 alkyl 3θi-6 alkyllg< R(DXVII), where LG' is a suitable life group; and form the compound of Formula (DXVI) from the compound of Formula (DXVII).

[181] In some embodiments, the compound formation step of Formula (DXVI) comprises the reaction of the compound of Formula (DXVII) with an azide group introducing agent to produce the compound of Formula (DXVI). In some embodiments, the azide group introducing agent is selected from the group consisting of NaN3, TMSN3, (PhO)2P(O)N3, Zn(N3)2*2Py and n-Bu4NN3.

[182] In some embodiments, LG' is selected from the group consisting of halogen, OTf, OMs and OTs.

[183] ​​In some embodiments, the compound of Formula (DXVII) has the structure of Formula (DXVIIa) or Formula (DXVIIb): Petition 870260086043, dated 08 / 24 / 2026, p. 51 / 389 46 / 328

[184] In some embodiments, the process for preparing a Formula (DII) compound may include the steps of: provide a compound of Formula (DIX) with the structure: (DIX), in which LG'' is a suitable life group; and form the compound of Formula (DXVII) from the compound of Formula (DIX).

[185] In some embodiments, LG'' is selected from the group consisting of halogen, OTf, OMs and OTs.

[186] In some embodiments, the compound formation step of Formula (DXVII) comprises: react the compound of Formula (DIX) with a compound of Formula (DXVIII): Petition 870260086043, dated 08 / 24 / 2026, p. 52 / 389 47 / 328 to produce the compound of Formula (DXVII).

[187] In some forms, the Formula (DIX) compound has the structure

[188] In some forms, the compound of Formula (DXVIII) has the structure of Formula (DXVIIIa):

[189] In some embodiments, the process for preparing a Formula (DII) compound may include the steps of: provide a compound of Formula (DXIX) with the structure: LG H0' / 1χ^ (Dxix), and form the compound of Formula (DIX) from the compound of Formula (DXIX).

[190] In some forms, the compound formation step of Formula (DIX) comprises: react the compound of Formula (DXIX) with a compound of Formula (DXV): LGt M LGV( (DXV), where LG' is a suitable co-existence group, to produce the compound of Formula (DXIX).

[191] In some embodiments, LG' is selected from the group consisting of halogen, OTf, OMs and OTs.

[192] In some forms, the compound of Formula (DXIX) Petition 870260086043, dated 08 / 24 / 2026, p. 53 / 389 48 / 328 has the structure of Formula (DXIXa): HD'^xO^''''^ (DXIXa).

[193] In some forms, the Formula (DXV) compound has the Formula (DXVa) structure: ^3Cl(DXVa) .

[194] In some embodiments, the process for preparing a Formula (DII) compound may include the steps of: provide a compound with formula (DXX) and the following structure: (DXX), and form the compound of Formula (DXIX) from the compound of Formula (DXX).

[195] In some embodiments, the step of forming the Formula (DXIX) compound comprises: react the compound of Formula (DXX) with an introducing agent LG” to produce the compound of Formula (DXIX).

[196] In some forms, the introducing agent LG” is NBu4Br3.

[197] In some forms, the Formula (DXX) compound has the Formula (DXXa) structure: (DXXa).

[198] In another aspect, a pharmaceutical composition comprising the peptidomimitic or compound of any of the embodiments described herein is provided here.

[199] In another aspect, a pharmaceutical dosage form comprising the peptidomimitic or compound of any of the embodiments described herein is provided herein.

[200] In another aspect, a method is provided here for selectively targeting GLP1R on the surface of a cell with Petition 870260086043, dated 08 / 24 / 2026, page 54 / 389 49 / 328 the peptidomimitic or compound of any of the embodiments described herein. In some embodiments, the cell is a mammalian cell. In some embodiments, the cell is a human cell. In some embodiments, the cell is a pancreatic cell, a brain cell, a heart cell, a vascular tissue cell, a kidney cell, an adipose tissue cell, a liver cell, or a muscle cell.

[201] In another aspect, a method is provided here for increasing GLP1R activity in an individual who needs it comprising administering to the individual an effective amount of the peptidomimitic or compound of any of the modalities described herein, of the composition described herein or of the dosage form described herein.

[202] In another aspect, a method is provided here for reducing blood glucose levels in an individual who needs it, comprising administering to the individual an effective amount of the peptidomimitic or compound of any of the embodiments described herein, of the composition described herein or of the dosage form described herein.

[203] In another aspect, a method is provided here for reducing body weight in an individual who needs it, comprising administering to the individual an effective amount of the peptidomimitic or compound of any of the modalities described herein, of the composition described herein or of the dosage form described herein.

[204] In another aspect, a method is provided here for treating a GLP1R-associated condition in a needy individual comprising administering to the individual an effective amount of the peptidomimitic or compound of any of the embodiments described herein, of the composition described herein or of the pharmaceutical form described herein. In some embodiments, the GLP1R-associated condition is type II diabetes, obesity, liver disease, coronary artery disease or kidney disease. In Petition 870260086043, dated 08 / 24 / 2026, p. 55 / 389 50 / 328 In some modalities, the condition associated with GLP1R is type II diabetes and / or obesity.

[205] In various embodiments of any of the methods described herein, the compound, composition or dosage form of the present disclosure is administered subcutaneously, intravenously, intradermally, intraperitoneally or intramuscularly.

[206] These and other aspects of the present disclosure will become apparent to those skilled in the subject after reading the following detailed description of the disclosure, including the appended claims. Brief Description of the Drawings

[207] The patent file or application contains at least one drawing executed in color. Copies of this patent publication or patent application with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[208] Figure 1 shows liquid-phase peptide support (LPPS) approaches for M1 production.

[209] Figure 2 shows the synthesis of Tag1-M2.

[210] Figure 3 shows the synthesis of Tag2-M2.

[211] Figure 4 shows the synthesis of Tag3-M2.

[212] Figure 5 shows the synthesis of Tag4-M2.

[213] Figure 6 shows the synthesis of Tag5-M1.

[214] Figure 7 shows the synthesis of Tag5-M3.

[215] Figure 8 shows some examples of known LPPS Tags.

[216] Figure 9 shows SPPS for peptide elongation.

[217] Figures 10A-B are tables that show a summary of the procedures and conditions used to prepare M1 using Tag5.

[218] Figures 11A-B are tables showing the elongation conditions and results used to produce M1 using Tag5.

[219] Figure 12 is a table showing the conditions of Petition 870260086043, dated 08 / 24 / 2026, page 56 / 389 51 / 328 elongation and the results used to produce M3 using Tag5.

[220] Figure 13 is a table showing a comparison of five routes used to prepare AA2 and AA2+Linker.

[221] Figure 14 shows the synthesis of AA2 using route 1.

[222] Figure 15 shows an alternative process for making AA2 and AA2+Linker. Detailed Description

[223] The present disclosure provides, in some respects, useful compounds as a support for liquid-phase organic synthesis. Several novel LPPS Tags (Tag2-Tag5 in Figure 1) were designed by a) increasing the hydrophobicity of the Tag for solidification of the TCP constituent to remove reagent and residual reagent, as well as impurities in solution for easy separation and purification; and b) introducing the 2,4-bismethoxybenzylamine amide moiety (e.g., in Tag5) for easy cleavage of the CN linkage, a GLP1 peptidomimetic was prepared in novel Tags after the synthesis of Fmoc / tBu C^N.

[224] Novel liquid-phase peptide support tags (LPPS) were designed to combine the advantages of solid-phase peptide support synthesis (SPPS), allowing the separation of solid-supported peptides from the elongation mixture, and classical solution-phase peptide synthesis (CSPS), using fewer molar equivalents of reagents and reagents for peptide chain growth. The greater hydrophobicity of LPPS tags allowed i) the performance of more peptide elongation steps on a Tag soluble in elongation solvents and ii) the precipitation of labeled carrier / growth peptides in polar solvents. Tag5, containing six long alkyl chains, allowed LPPS of a hydrophilic GLP1 agonist, using fewer molar equivalents of reagents and reagents compared to SPPS synthesis.

[225] Detailed modalities of the present disclosure are revealed here; however, it should be understood that the modalities Petition 870260086043, dated 08 / 24 / 2026, page 57 / 389 52 / 328 disclosed are merely illustrative of the disclosure, which may be incorporated in various forms. Furthermore, each of the examples provided in connection with the various embodiments of the disclosure is intended to be illustrative and not restrictive. Therefore, the specific structural and functional details disclosed herein should not be interpreted as limiting, but merely as a representative basis for teaching a person skilled in the art how to employ the present disclosure in various ways. Definitions

[226] Unless defined otherwise, all technical and scientific terms used herein have the same meaning commonly understood by a person skilled in the subject matter to which this disclosure pertains.

[227] As used in this specification and the accompanying claims, the singular forms a, an and the include plural references, unless the context clearly indicates otherwise. Thus, for example, a reference to a method includes one or more methods and / or steps of the type described herein and / or which will become apparent to those skilled in the art after reading this disclosure.

[228] A subject or patient or individual or animal, as used herein, refers to humans, veterinary animals (e.g., cats, dogs, cows, horses, sheep, pigs, etc.) and experimental animal models of disease (e.g., mice, rats). In a preferred embodiment, the individual is a human being.

[229] The term pharmaceutically acceptable salt, as used in relation to the compositions of the present disclosure, refers to any salt suitable for administration to a patient. Suitable salts include, but are not limited to, those disclosed in Berge et al., Pharmaceutical Salts, J. Pharm. Sci., 1977, 66:1, incorporated herein by reference. Examples of salts include, but are not limited to, acid-derived salts, Petition 870260086043, dated 08 / 24 / 2026, page 58 / 389 53 / 328 base derivatives, organic, inorganic, amine and alkali or alkaline-earth metals, including, but not limited to, calcium salts, magnesium salts, potassium salts, sodium salts, hydrochloric acid salts, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, para-toluenesulfonic acid, salicylic acid and the like.

[230] Ranges may be expressed here as from about or approximately a specific value and / or up to about or approximately another specific value. When such a range is expressed, another embodiment includes from a specific value and / or up to the other specific value.

[231] By “comprising” or “containing” or “including” it is understood that at least the named compound, element, particle or method step is present in the composition or article or method, but does not exclude the presence of other compounds, materials, particles or method steps, even if the other compounds, materials, particles or method steps have the same function as the one named.

[232] The compounds of the present disclosure, as Tags, include those described herein in general and are further illustrated by the classes, subclasses, and species disclosed herein. As used herein, the following definitions apply unless otherwise indicated. For the purposes of this disclosure, chemical elements are identified according to the Periodic Table of Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed. In addition, the general principles of organic chemistry are described in “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999, and “March's Advanced Organic Chemistry”, 5th Ed., Ed.: Smith, MB and March, J., John Petition 870260086043, dated 08 / 24 / 2026, page 59 / 389 54 / 328 Wiley & Sons, New York: 2001, the full content of which is incorporated herein by reference.

[233] As used herein, the term alkyl receives its common meaning in the art and may include saturated aliphatic groups, including straight-chain alkyl groups and branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl-substituted cycloalkyl groups, and cycloalkyl-substituted alkyl groups. In certain embodiments, a straight-chain or branched-chain alkyl has about 1 to 30 carbon atoms in its main chain (e.g., C1-C30 for straight-chain, C2-C30 for branched-chain) and, alternatively, about 1 to 10 carbon atoms, or about 1 to 6 carbon atoms. In some embodiments, a cycloalkyl ring has about 3 to 10 carbon atoms in its ring structure, where such rings are monocyclic or bicyclic, and, alternatively, about 5, 6, or 7 carbons in the ring structure.In some embodiments, an alkyl group may be a lower alkyl group, where a lower alkyl group comprises from 1 to 5 carbon atoms (e.g., C1-C5 for straight-chain lower alkyl).

[234] The term halogen means F, Cl, Br or I; the term halide refers to a halogen radical or substituent, that is, -F, -Cl, -Br or -I.

[235] As described herein, the developing compounds (e.g., Tags) may contain optionally substituted moieties. In general, the term substituted, preceded or not by the term optionally, means that one or more hydrogens of the designated moiety are replaced by a suitable substituent. For example, up to three H atoms in each residue are replaced by alkyl, halogen, haloalkyl, hydroxyl, lower alkoxy, carboxyl, carboalkoxy (also known as alkoxycarbonyl), carboxamido (also known as alkylaminocarbonyl), cyano, carbonyl, nitro, amino, Petition 870260086043, dated 08 / 24 / 2026, p. 60 / 389 55 / 328 alkylamino, dialkylamino, mercapto, alkylthio, sulfoxide, sulfone, acylamino, amidino, phenyl, benzyl, heteroaryl, phenoxy, benzyloxy or heteroaryloxy. Unless otherwise indicated, an optionally substituted group may have a suitable substituent at each replaceable position of the group, and where more than one position in any given structure may be substituted by more than one substituent selected from a given group, the substituent may be the same or different at each position. The combinations of substituents provided for in this disclosure are preferably those that result in the formation of stable or chemically viable compounds.

[236] The term stable, as used here in reference to compounds, refers to compounds that are not substantially altered when subjected to conditions that allow their production, detection and, in certain embodiments, their recovery, purification and use for one or more of the purposes disclosed herein.

[237] Unless otherwise indicated, the structures described herein shall also include all isomeric forms (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) of the structure; for example, the R and S configurations for each asymmetric center, double bond isomers (Z) and (E), and conformational isomers (Z) and (E). Therefore, simple stereochemical isomers, as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the compounds present, are within the scope of the present disclosure.

[238] Unless otherwise indicated, cyclic adducts, for example, products of a cycloaddition reaction, such as an azide-acetylene cycloaddition reaction or a Diels-Alder reaction, described herein, include all regioisomers, that is, structural isomers that differ only in the position of a functional group or substituent. By way of example, the Petition 870260086043, dated 08 / 24 / 2026, page 61 / 389 56 / 328 The following structures represent regioisomers of triazoles, which differ only in the position of the substituent on the triazole ring: * < \n Λνζ\-** nn N_N and . . Triazole regioisomers also They can be represented by the following structure: > NN .

[239] Unless otherwise indicated, all tautomeric forms of the disclosure compounds are within the scope of the disclosure.

[240] Furthermore, unless otherwise indicated, the structures described herein shall also include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds with the structures presented, except for the substitution of hydrogen by deuterium or tritium, or for the substitution of a carbon by a carbon enriched in 11C, 13C or 14C, are within the scope of this disclosure.

[241] It should also be understood that mentioning one or more steps of the method does not preclude the presence of additional steps or intervening steps between those expressly identified. Similarly, it should also be understood that mentioning one or more components in a device or system does not preclude the presence of additional components or intervening components between those expressly identified.

[242] Unless otherwise indicated, all crystalline forms of the developing compounds and their salts are also within the scope of the developing compounds. The developing compounds may be isolated in various amorphous and crystalline forms, including, without limitation, anhydrous, hydrated, non-solvated, or solvated forms. Exemplary hydrates include hemihydrates, monohydrates, dihydrates, and the like. In some embodiments, the developing compounds are anhydrous and non-solvated. By anhydrous it is understood that the crystalline form of the compound does not contain Petition 870260086043, dated 08 / 24 / 2026, p. 62 / 389 57 / 328 essentially water bound in the crystalline structure, meaning the compound does not form a crystalline hydrate.

[243] As used herein, crystalline form refers to a particular lattice configuration of a crystalline substance. Different crystalline forms of the same substance typically exhibit different crystal lattices (e.g., unit cells), which are attributed to different physical properties characteristic of each crystalline form. In some cases, different lattice configurations exhibit different water or solvent contents. Different crystal lattices can be identified by solid-state characterization methods, such as powder X-ray diffraction (PXRD). Other characterization methods, such as differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), solid-state NMR, and the like, further assist in identifying the crystalline form, as well as in determining stability and solvent / water content.

[244] The crystalline forms of a substance include solvated (e.g., hydrated) and non-solvated (e.g., anhydrous) forms. A hydrated form is a crystalline form that includes water in the crystal structure. Hydrated forms can be stoichiometric hydrates, where water is present in the structure in a specific water / molecule ratio, such as for hemihydrates, monohydrates, dihydrates, etc. Hydrated forms can also be non-stoichiometric, where the water content is variable and dependent on external conditions such as humidity.

[245] In some embodiments, the developing compounds are substantially isolated. By substantially isolated it is understood that a specific compound is at least partially isolated from impurities. For example, in some embodiments, a developing compound comprises less than about 50%, less than about 40%, less than about 30%, less than about 20%, less Petition 870260086043, dated 08 / 24 / 2026, p. 63 / 389 58 / 328 of about 15%, less than about 10%, less than about 5%, less than about 2.5%, less than about 1%, or less than about 0.5% of impurities. Impurities generally include anything other than the substantially isolated compound, including, for example, other crystalline forms and other substances.

[246] The term GLP1R refers to the glucagon-like peptide receptor 1 and includes the recombinant GLP1R protein or a fragment thereof. GLP1R has a sequence of 463 residues. Donnelly, Br J Pharmacol, 166(1):27-41 (2011). Glucagon-like peptide 1 (GLP1) is a 31-amino acid peptide hormone released by intestinal L cells after nutrient consumption. GLP1 binding to GLP1R potentiates glucose-induced insulin secretion by pancreatic beta cells, increases insulin expression, inhibits beta cell apoptosis, promotes beta cell neogenesis, reduces glucagon secretion, delays gastric emptying, promotes satiety, and increases peripheral glucose clearance. Tags

[247] In accordance with the above and other objectives, the present disclosure provides compounds, precursors and intermediates thereof, which can be used as Tags for the preparation of GLP1 peptidomimetics. The present disclosure also provides methods for the production of these compounds, precursors and intermediates thereof.

[248] Also provided in the present disclosure are GLP1 peptidomimetics prepared using the Tags described herein and pharmaceutical compositions comprising GLP1 peptidomimetics, and methods for treating certain diseases in an individual requiring such treatment.

[249] In one aspect, the present disclosure provides a compound with a structure of Formula (I): Petition 870260086043, dated 08 / 24 / 2026, page 64 / 389 59 / 328 in which: men are, independently, an integer from 1 to 5, and (m+n)>3; R1 is a C1-5 alkyl; R2 is, independently in each occurrence, an optionally substituted C10-30 alkyl; and R3 is, independently in each occurrence, an optionally substituted C10-30 alkyl group, or a salt thereof.

[250] According to the present revelation, m can be an integer from 1 to 5 and n can be an integer from 1 to 5, provided that (m+n)>3. For example, m can be 1, 2, 3, 4 or 5 and n can be 1, 2, 3, 4 or 5.

[251] In at least one form, m is 3 and en is 3.

[252] According to the present disclosure, R1 can be methyl, ethyl, propyl, butyl or pentyl. For example, R1 can be n-propyl, i-propyl, n-butyl, i-butyl, t-butyl or n-pentyl. In at least one embodiment, R1 is methyl.

[253] According to the present disclosure, R2 is, independently in each occurrence, an optionally substituted C10-30 alkyl. For example, a C10-30 alkyl may be optionally substituted from 1 to 10 times by a substituent selected from the group consisting of halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy (also known as alkoxycarbonyl), carboxamide (also known as Petition 870260086043, dated 08 / 24 / 2026, page 65 / 389 60 / 328 alkylaminocarbonyl), cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy. For example, the C10-30 alkyl may be optionally substituted 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 times with any of the substituents described above, wherein each substituent is independently selected from halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy, carboxamido, cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy.

[254] According to the present disclosure, R3 is, independently in each instance, an optionally substituted C10-30 alkyl. For example, a C10-30 alkyl may be optionally substituted from 1 to 10 times by a substituent selected from halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy (also known as alkoxycarbonyl), carboxamide (also known as alkylaminocarbonyl), cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy. For example, the C10-30 alkyl group may be optionally substituted 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 times with any of the substituents described above, wherein each substituent is independently selected from halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy, carboxamido, cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy.

[255] In at least one embodiment, R2 is, independently in each instance, an optionally substituted C18-26 alkyl, and R3 is, independently in each instance, an optionally substituted C18-26 alkyl. For example, each R2 is, independently, an optionally substituted C22 alkyl and each R3 is, independently, an optionally substituted C22 alkyl.

[256] In one aspect, a compound with a Formula (Ia) structure is given here: Petition 870260086043, dated 08 / 24 / 2026, p. 66 / 389 61 / 328 (Ia), or a salt of it.

[257] In another aspect, the present disclosure provides a process for preparing a compound of Formula (I): (I), where: men are, independently, an integer from 1 to 5, and (m+n)>3; R1 is a C1-5 alkyl; R2 is, independently in each occurrence, an optionally substituted C10-30 alkyl; and R3 is, independently in each occurrence, an optionally substituted C10-30 alkyl group, or a salt thereof. This process includes: (a) provide a compound of Formula (II) with the structure: Petition 870260086043, dated 08 / 24 / 2026, p. 67 / 389 62 / 328 (II), in which PG is a suitable protecting group; and (b) form the compound of Formula (I) from the compound of Formula (II).

[258] According to the present disclosure, PG is any suitable protecting group that can be used to protect the amino group. Suitable protecting groups that can be used are known to those skilled in the art. A detailed description of such groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Press, New York, 1981, which is incorporated herein by reference in its entirety. For example, PG can be selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc), and 9-fluorenylmethoxycarbonyl (Fmoc). In some embodiments, PG is allyloxycarbonyl (Alloc).

[259] In some forms, the compound of Formula (II) has the structure of Formula (IIa): Petition 870260086043, dated 08 / 24 / 2026, p. 68 / 389 63 / 328

[260] In some embodiments, step (b) of forming the compound of Formula (I) may include reacting the compound of Formula (II) with a protecting group removing agent to produce the compound of Formula (I).

[261] According to the present disclosure, any suitable protecting group scavenging agent can be used to remove the PG protecting group from the amino group of the compound of Formula (II). Suitable protecting group scavenging agents that can be used to remove a specific protecting group are known to those skilled in the art. A detailed description of such groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Press, New York, 1981, which is incorporated herein by reference in its entirety. For example, the protecting group scavenging agent is selected from the group consisting of Pd(PPh)3, PhSiH3, H2, piperidine and trifluoroacetic acid (TFA).

[262] In some embodiments, the process of preparing a compound of Formula (I) may include a step of providing a compound of Formula (III) with the structure: oz R1 (III) ; in which PG1 is an adequate protective group; PG2 is a suitable protecting group; and form the compound of Formula (II) from the compound of Formula (III) before step (a).

[263] According to the present disclosure, PG1 is any group Petition 870260086043, dated 08 / 24 / 2026, p. 69 / 389 64 / 328 suitable protecting group that can be used to protect the hydroxyl group. Suitable protecting groups that can be used are known to those skilled in the art and can be selected from those described in Handbook of Reagents for Organic Synthesis. Activating Reagents and Protecting Groups, Pearson and Roush, Eds., John Wiley & Sons, 2005, which is incorporated herein by reference in its entirety. For example, PG1 can be selected from the group consisting of tert-butyldimethylsilyl (TBS), trimethylsilyl (TMS), triethylsilyl (TES), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS).

[264] According to the present disclosure, PG2 is any suitable protecting group that can be used to protect the hydroxyl group. Suitable protecting groups that can be used are known to those skilled in the art and can be selected from those described in Handbook of Reagents for Organic Synthesis. Activating Reagents and Protecting Groups, Pearson and Roush, Eds., John Wiley & Sons, 2005, which is incorporated herein by reference in its entirety. For example, PG2 can be selected from the group consisting of tert-butyldimethylsilyl (TBS), trimethylsilyl (TMS), triethylsilyl (TES), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS).

[265] According to the present revelation, each PG1 and each PG2 can be equal or different. In some embodiments, PG1 is equal to group PG2. For example, if m is 3 and n is 3, each of the three groups PG1 is equal and each of the three groups PG2 is equal, and PG1 = PG2. In some embodiments, PG1 is TBS and PG2 is TBS. Alternatively, PG1 and PG2 can be different from each other. For example, if m is 3 and n is 3, each of the three groups PG1 (PG11, PG12 and PG13) are equal (PG1 = PG11 = PG12 = PG13) and each of the three groups PG2 (PG21, PG22 and PG23) are equal (PG2 = PG21 = PG22 = PG23), but PG1 is different from PG2. In some modalities, PG1 is Petition 870260086043, dated 08 / 24 / 2026, p. 70 / 389 65 / 328 TBS and PG2 are TIPS. Alternatively, each PG1 and each PG2 can be different from each other. For example, if m is 3 and n is 3, each of the three PG1 groups will be different from each other (PG11 is different from PG12, PG12 is different from PG13, and PG11 is different from PG13) and each of the three PG2 groups will be the same (PG21 is different from PG22, PG22 is different from PG23, and PG21 is different from PG23), and none of the PG11, PG12, PG13, PG21, PG22, and PG23 will be the same.

[266] In some forms, the Formula (III) compound has the Formula (IIIa) structure:

[267] In some embodiments, the compound formation step of Formula (II) before step (a) comprises: react the compound of Formula (III) with a protecting group removing agent to obtain an unprotected intermediate; react the said intermediate with at least one compound of Formula (IV): R-LG (IV), where R is an optionally substituted C10-30 alkyl; and LG is a suitable output group; to produce the compound of Formula (II).

[268] According to the present disclosure, any suitable protecting group stripping agent can be used to remove the PG1 and PG2 protecting groups from the hydroxyl groups of the compound of Formula (III). Suitable protecting group stripping agents that can be used to remove a protecting group Petition 870260086043, dated 08 / 24 / 2026, page 71 / 389 66 / 328 specific are known to persons skilled in the art and may be selected from those described in “Handbook of Reagents for Organic Synthesis. Activating Reagents and Protecting Groups”, Pearson and Roush, Eds., John Wiley & Sons, 2005, which is incorporated herein by reference in its entirety. For example, the protecting group removing agent may be selected from the group consisting of tetrabutylammonium fluoride (TBAF), NH4F, SiF4, AcOH, HCl, LiAlH4 and K2CO3.

[269] In some embodiments, if PG1 and PG2 are different from each other, different protecting group scavenging agents can be used. In this case, a protecting group scavenging agent can be used to selectively remove all PG1 groups present in the compound of Formula (III). Then, the intermediate formed can react with the first compound of Formula (IV), compound of Formula (IVa). Then, another protecting group scavenging agent can be used to selectively remove all PG2 groups, and then another compound of Formula (IV), compound of Formula (IVb), can be used to modify the unprotected hydroxyl groups. In this case, the compound of Formula (IVa) can be different from the compound of Formula (IVb).

[270] According to the present disclosure, LG is a suitable output group. Suitable output groups may be used, according to the knowledge of those skilled in the art. For example, LG may be selected from a group consisting of halogen, OTf, OMs and OTs.

[271] In some embodiments, the process for preparing a compound of Formula (I) may include a step of: provide a compound of Formula (V) with the structure: Petition 870260086043, dated 08 / 24 / 2026, p. 72 / 389 67 / 328 form the compound of Formula (III) from the compound of Formula (V).

[272] In some embodiments, the compound formation step of Formula (III) may comprise: react the compound of Formula (V) with a compound of Formula (VIa) or Formula (VIb): PG-X (VIa) or PG2O (VIb), where X is Cl or Br; to produce the compound of Formula (III).

[273] According to the present disclosure, suitable compounds of Formula (VIa) or Formula (VIb) may be selected, but are not limited to, the group consisting of AllocCl, Alloc2O, Cbz2O, CbzCl, FmocCl and Boc2O.

[274] In some embodiments, the process for preparing a compound of Formula (I) may include a step of: provide a compound of Formula (VII) with the structure: (VII); Petition 870260086043, dated 08 / 24 / 2026, p. 73 / 389 68 / 328 where PG3 is a suitable protecting group; and form the compound of Formula (V) from the compound of Formula (VII).

[275] According to the present disclosure, PG3 is any suitable protecting group that can be used to protect the amino group. Suitable protecting groups that can be used are known to those skilled in the art. A detailed description of such groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Press, New York, 1981, which is incorporated herein by reference in its entirety. For example, PG3 can be selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc), and 9-fluorenylmethoxycarbonyl (Fmoc). In some embodiments, PG3 is 9-fluorenylmethoxycarbonyl (Fmoc).

[276] In some forms, the compound of Formula (VII) has the following structure: OTBS (VIIa).

[277] In some embodiments, the process for preparing a compound of Formula (V) includes reacting the compound of Formula (VII) with a protecting group removing agent to produce the compound of Formula (V).

[278] According to the present disclosure, any suitable shielding group stripper can be used to remove the PG3 shielding group from the amino group of the compound of Formula (VII). Suitable shielding group strippers that can be Petition 870260086043, dated 08 / 24 / 2026, page 74 / 389 69 / 328 used to remove a specific protecting group are known to those skilled in the art. A detailed description of these groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Press, New York, 1981, which is incorporated herein by reference in its entirety. For example, the protecting group removing agent is selected from the group consisting of Pd(PPh)3, PhSiH3, H2, piperidine and trifluoroacetic acid (TFA).

[279] In some embodiments, the process for preparing a compound of Formula (I) may include a step of: provide a compound of Formula (VIII) with the structure: (VIII); and forming the compound of Formula (VII) from the compound of Formula (VIII).

[280] In some embodiments, the process of forming the compound of Formula (VII) may involve the reaction of the compound of Formula (VIII) with a compound of Formula (IX) with the structure: to produce the compound of Formula (VII).

[281] In one embodiment, the compound of Formula (VIII) has the following structure: Petition 870260086043, dated 08 / 24 / 2026, p. 75 / 389 70 / 328 (Villa).

[282] In another embodiment, the compound of Formula (IX) has the following structure: (IXa).

[283] In some embodiments, the process for preparing a compound of Formula (I) may include a step of: providing a compound of Formula (X) with the structure: where PG4 is a suitable protecting group; and form the compound of Formula (VIII) from the compound of Formula (X).

[284] According to the present disclosure, PG4 is any suitable protecting group that can be used to protect the amino group. Suitable protecting groups that can be used are known to those skilled in the art. A detailed description of these groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Press, New York, 1981, which is incorporated herein by reference in its entirety. For example, PG4 can be selected from the group consisting of allyl, allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc), and 9-fluorenylmethoxycarbonyl (Fmoc). In some embodiments, PG4 is allyl. Petition 870260086043, dated 08 / 24 / 2026, page 76 / 389 71 / 328

[285] In one embodiment, the compound of Formula (X) has the following structure: TBSO OTBS OTBS (Xa).

[286] In some embodiments, the process of forming the compound of Formula (VIII) includes the reaction of the compound of Formula (X) with a protecting group removing agent.

[287] According to the present disclosure, any suitable shielding agent can be used to remove the PG4 shielding group from the amino group of the compound of Formula (X). Suitable protective group stripping agents that can be used to remove a specific protective group are known to those skilled in the art. A detailed description of these groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Press, New York, 1981, which is incorporated herein by reference in its entirety. For example, the protective group stripping agent is selected from the group consisting of Pd / K2CO3, 1,3-dimethylbarbituric acid / Pd(PPh3)4, Pd(PPh)3, PhSiH3, H2, piperidine, and trifluoroacetic acid (TFA).

[288] In some embodiments, the process for preparing a compound of Formula (I) may include a step of: provide a compound of Formula (XI) with the structure: Jj / X(O-PG1)m The (XI); and form the compound of Formula (X) from the compound of Formula (XI).

[289] In one embodiment, the compound of Formula (XI) has the following structure: Petition 870260086043, dated 08 / 24 / 2026, p. 77 / 389 72 / 328 OTBS TBSO.Á. TBSO (XIa) .

[290] In some embodiments, the process of forming the compound of Formula (X) comprises: react the compound of Formula (XI) with a compound of Formula (XII): ^^NH2 (XII), or a salt thereof, to produce the compound of Formula (X).

[291] In some embodiments, the process for preparing a compound of Formula (I) may include a step of: provide a compound of Formula (XIII) with the structure: OH (XIII); and form the compound of Formula (XI) from the compound of Formula (XIII).

[292] In one embodiment, the compound of Formula (XIII) has the following structure: OTBS TBSO^ / L· JL .OH TBSO (XIIIa) .

[293] In some embodiments, the process for forming the compound of Formula (XI) involves reacting the compound of Formula (XIII) with an oxidizing agent to produce the compound of Formula (XI).

[294] According to the present disclosure, any suitable oxidizing agent that can convert the primary alcohol into the aldehyde group can be used. Suitable oxidizing agents that can be used are known as technical in the subject. For example, the oxidizing agent can be selected from the group that Petition 870260086043, dated 08 / 24 / 2026, p. 78 / 389 73 / 328 consists of pyridinium chlorochromate (PCC), pyridinium dichromate (PDC), silver carbonate (Ag2CO3), tetra-n-propylammonium perruthenate (TPAP) and Dess-Martin periodinane (DMP).

[295] In some embodiments, the process for preparing a compound of Formula (I) may include a step of: provide a compound of Formula (XIV) with the structure: 0(XIV), where Y is -OC1-6 alkyl; and form the compound of Formula (XIII) from the compound of Formula (XIV).

[296] In one embodiment, the compound of Formula (XIV) has the following structure: OTBS TBSO^J\ XLo tbsoO(XIVa) .

[297] In some embodiments, the process of forming the compound of Formula (XIII) involves the reaction of the compound of Formula (XIV) with a reducing agent.

[298] According to the present disclosure, any suitable reducing agent that can convert the ester into the primary alcohol group can be used. Suitable reducing agents that can be used are known as technically skilled agents in the art. For example, the reducing agent is selected from the group consisting of LiAlH4, DIBALH and LiBH4.

[299] In some embodiments, the process for preparing a compound of Formula (I) may include a step of: provide a compound of Formula (XV) with the structure: Petition 870260086043, dated 08 / 24 / 2026, p. 79 / 389 74 / 328 (XV); and form the compound of Formula (XIV) from the compound of Formula (XV).

[300] In one embodiment, the compound of Formula (XV) has the following structure: OH HO HO °\ (XVa) .

[301] In some embodiments, the process of forming the compound of Formula (XIV) comprises the reaction of the compound of Formula (XV) with a protecting group introducing agent to produce the compound of Formula (XIV).

[302] According to the present disclosure, any suitable protecting group introducing agent can be used to protect the hydroxyl groups in the compound of Formula (XV). Suitable protecting group introducing agents that can be used are known to those skilled in the art. In some embodiments, the protecting group introducing agent is selected from the group consisting of TBSCl, TBSOTf, TMSCl, TMSOTf, TESCl, TESOTf, TBDPSCl, TBDPSOTf, TIPSCl and TIPSOTf.

[303] In another aspect, the present disclosure provides a product prepared in accordance with any of the methods described in the present disclosure.

[304] In one embodiment, the product is a compound of Formula (I): Petition 870260086043, dated 08 / 24 / 2026, p. 80 / 389 75 / 328 where: men are, independently, an integer from 1 to 5, and (m+n)>3; R1 is a C1-5 alkyl; R2 is, independently in each occurrence, a optionally substituted C10-30 alkyl; and R3 is, independently in each occurrence, a Optionally substituted C10-30 alkyl or a salt thereof.

[305] In another product category, it is a compound of formula THE (Ia) or a salt of it.

[306] In another aspect, this revelation provides a method of using a compound of Formula (I): Petition 870260086043, dated 08 / 24 / 2026, p. 81 / 389 76 / 328 in which: men are, independently, an integer (m+n)>3; R1 is a C1-5 alkyl; R2 is, independently in each occurrence, an optionally substituted one; and R3 is, independently in each occurrence, an optionally substituted, or a salt thereof, to produce a peptide or a peptidomimetic.

[307] In at least one embodiment, the compound is used as a carrier or a tag to produce a peptidomimetic.

[308] In one embodiment, the peptidomimetic is a Formula: from 1 to 5, and C10-30 alkyl C10-30 alkyl Formula (I) peptide or compound of or a salt of the same.

[309] In one embodiment, the peptidomimetic is a Formula: composed of Petition 870260086043, dated 08 / 24 / 2026, page 82 / 389 77 / 328 or a salt of the same.

[310] In another aspect, the present disclosure provides a compound manufactured using a compound of Formula (I): in which: men are, independently, an integer from 1 to 5, and (m+n)>3; R1 is C1-5 alkyl; R2 is selected independently at each occurrence of a C10-30 optionally substituted alkyl; and R3 is selected independently at each occurrence of a Optionally substituted C10-30 alkyl, or a salt thereof.

[311] In one form, the compound has a formula: Petition 870260086043, dated 08 / 24 / 2026, p. 83 / 389 78 / 328 h2n or a salt of it. one Formula: HN'N OH / NH N

[312] In one embodiment, the compound has NH2 OH Nf<2 o n=no JU / 1ou um sal dele.

[313] The present disclosure provides a compound with a structure of Formula (AI): (THERE) The one in which: men are, independently, an integer number of 5; R1a is C1-5 alkyl; R2a is, independently in each occurrence, a optionally substituted C10-30 alkyl; and R3aé, independently in each occurrence, a Optionally substituted C10-30 alkyl, or a salt thereof.

[314] According to the present revelation, m can be a number Petition 870260086043, dated 08 / 24 / 2026, p. 84 / 389 79 / 328 is an integer from 0 to 5. For example, m can be 0, 1, 2, 3, 4, or 5, and en can be 0, 1, 2, 3, 4, or 5.

[315] According to the present disclosure, R1a can be methyl, ethyl, propyl, butyl, or pentyl. For example, R1 can be n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, or n-pentyl. In at least one embodiment, R1a is methyl.

[316] According to the present disclosure, R2a is, independently in each instance, an optionally substituted C10-30 alkyl. For example, a C10-30 alkyl may be optionally substituted from 1 to 10 times by a substituent selected from halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy (also known as alkoxycarbonyl), carboxamide (also known as alkylaminocarbonyl), cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy. For example, the C10-30 alkyl group may be optionally substituted 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 times with any of the substituents described above, wherein each substituent is independently selected from halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy, carboxamido, cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy.

[317] According to the present disclosure, R3a is, independently in each instance, an optionally substituted C10-30 alkyl. For example, a C10-30 alkyl may be optionally substituted from 1 to 10 times by a substituent selected from halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy (also known as alkoxycarbonyl), carboxamido (also known as alkylaminocarbonyl), cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy. For example, the C10-30 alkyl may be optionally substituted 1, 2, 3, 4, 5, 6, Petition 870260086043, dated 08 / 24 / 2026, page 85 / 389 80 / 328 7, 8, 9 or 10 times with any of the substituents described above, wherein each substituent is independently selected from halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy, carboxamido, cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy.

[318] In at least one embodiment, R2a is, independently in each instance, an optionally substituted C18-26 alkyl, and R3a is, independently in each instance, an optionally substituted C18-26 alkyl. For example, each R2a is, independently, an optionally substituted C22 alkyl and each R3a is, independently, an optionally substituted C22 alkyl.

[319] The present disclosure provides a compound with a structure of Formula (BI): The (BI) at 5; in which: m is an integer of R1bé C1-5 alkyl; and R2bé, independently optionally replaced; or a salt of it.

[320] According to the present revelation, m can be an integer from 1 to 5. For example, m can be 1, 2, 3, 4, or 5.

[321] According to the present disclosure, R1b can be methyl, ethyl, propyl, butyl or pentyl. For example, R1b can be n-propyl, i-propyl, n-butyl, i-butyl, t-butyl or n-pentyl. In at least one embodiment, R1b is methyl.

[322] According to the present disclosure, R2bé, in each occurrence, is a C10-30 alkyl Petition 870260086043, dated 08 / 24 / 2026, p. 86 / 389 81 / 328 independently in each occurrence, an optionally substituted C10-30 alkyl. For example, a C10-30 alkyl may be optionally substituted from 1 to 10 times by a substituent selected from halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy (also known as alkoxycarbonyl), carboxamide (also known as alkylaminocarbonyl), cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy. For example, the C10-30 alkyl group may be optionally substituted 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 times with any of the substituents described above, wherein each substituent is independently selected from halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy, carboxamido, cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy.

[323] In at least one embodiment, R2bé, independently in each occurrence, an optionally substituted C18-26 alkyl. For example, each R2bé, independently, an optionally substituted C22 alkyl.

[324] The present disclosure provides a compound with a in which: men are, independently, an integer from 1 to 5, and (m+n)>3; R2cé, independently in each occurrence, is an optionally substituted C10-30 alkyl; and R3cé, independently in each occurrence, is an optionally substituted C10-30 alkyl, Petition 870260086043, dated 08 / 24 / 2026, p. 87 / 389 82 / 328 or one of its salts.

[325] According to the present revelation, m can be an integer from 1 to 5 and n can be an integer from 1 to 5, provided that (m+n)>3. For example, m can be 1, 2, 3, 4 or 5 and n can be 1, 2, 3, 4 or 5.

[326] According to the present disclosure, R2 is, independently in each instance, an optionally substituted C10-30 alkyl. For example, a C10-30 alkyl may be optionally substituted from 1 to 10 times by a substituent selected from halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy (also known as alkoxycarbonyl), carboxamide (also known as alkylaminocarbonyl), cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy. For example, the C10-30 alkyl group may be optionally substituted 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 times with any of the substituents described above, wherein each substituent is independently selected from halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy, carboxamido, cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy.

[327] According to the present disclosure, R3 is, independently in each instance, an optionally substituted C10-30 alkyl. For example, a C10-30 alkyl may be optionally substituted 1 to 10 times by a substituent selected from halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy (also known as alkoxycarbonyl), carboxamide (also known as alkylaminocarbonyl), cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy. For example, C10-30 alkyl may be optionally substituted 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 times with any of the substituents described above, where each substituent is independently selected. Petition 870260086043, dated 08 / 24 / 2026, p. 88 / 389 83 / 328 including halogen, hydroxyl, lower alkoxy, carboxyl, carboalkoxy, carboxamide, cyano, nitro, amino, alkylamino, dialkylamino, mercapto, alkylthio, phenyl, benzyl, heteroaryl, phenoxy or benzyloxy.

[328] In at least one embodiment, R2 is, independently in each instance, an optionally substituted C18-26 alkyl, and R3 is, independently in each instance, an optionally substituted C18-26 alkyl. For example, each R2 is, independently, an optionally substituted C22 alkyl and each R3 is, independently, an optionally substituted C22 alkyl. Methods for producing a peptide or peptidomimetic using Tags

[329] The present disclosure provides a method for producing a peptide or a peptidomimetic, the method comprising the steps of: (a) provide a compound of Formula (I): in which: men are, independently, an integer from 1 to 5, and (m+n)>3; R1 is C1-5 alkyl; R2 is selected independently at each occurrence of a C10-30 optionally substituted alkyl; and R3 is selected independently at each occurrence of a C10-30 alkyl optionally substituted, or a salt thereof; Petition 870260086043, dated 08 / 24 / 2026, p. 89 / 389 84 / 328 (b) provide a first amino acid (AA1); and (c) couple the first amino acid (AA1) to the compound of Formula (I) to form a peptide bond between the first amino acid (AA1) and the compound of Formula (I).

[330] The term amino acid refers to a molecule that contains an amino group and a carboxyl group. Amino acids include alpha-amino acids and beta-amino acids, whose structures are illustrated below. In certain embodiments, an amino acid is a

[331] Suitable amino acids that may be used in accordance with the present disclosure include, without limitation, i) natural alpha-amino acids, such as the D and L isomers of the 20 common natural alpha-amino acids found in peptides and proteins: Alanine, Arginine, Asparagine, Aspartic Acid, Cysteine, Glutamic Acid, Glutamine, Glycine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline, Serine, Threonine, Tryptophan, Tyrosine, Valine and their derivatives; ii) non-natural alpha-amino acids; iii) natural beta-amino acids (e.g., beta-alanine) and iv) non-natural beta-amino acids.

[332] In one embodiment, step (c) of coupling AA1 to compound of Formula (I) comprises coupling the carboxylic acid moiety of AA1 with the amino moiety of compound of Formula (I).

[333] In some embodiments, the first amino acid (AA1) contains a protected amino group.

[334] In one embodiment, the first amino acid (AA1) is Petition 870260086043, dated 08 / 24 / 2026, page 90 / 389 85 / 328

[335] In some embodiments, the method of producing a peptide or a peptidomimetic may include a step of activating the chemical groups on the first amino acid (AA1) to prepare the first amino acid (AA1) for coupling with the compound of Formula (I) before step (c).

[336] In some embodiments, the method of producing a peptide or a peptidomimetic may include the steps of: (d) remove the protecting group from the first amino acid (AA1); (e) provide a second amino acid (AA2); and (f) couple the second amino acid (AA2) to the first amino acid (I-AA1) to form a peptide bond between the second amino acid (AA2) and the first amino acid (I-AA1-AA2).

[337] In one embodiment, step (f) comprises coupling the carboxylic acid moiety of AA2 with the amino moiety of AA1.

[338] In one embodiment, the second amino acid (AA2) is

[339] In some embodiments, the method of producing a peptide or a peptidomimetic may include the steps of: (g) remove the protecting group from the second amino acid (AA2); (h) provide a third amino acid (AA3); and (i) couple the third amino acid (AA3) to the second amino acid to form a peptide bond between the third amino acid (AA3) and the second amino acid (I-AA1-AA2-AA3).

[340] In one embodiment, step (i) comprises coupling the carboxylic acid moiety of AA3 with the amino moiety of AA2.

[341] In one embodiment, the third amino acid (AA3) is Petition 870260086043, dated 08 / 24 / 2026, page 91 / 389 86 / 3281O NHFmoc .

[342] In some embodiments, the method of producing a peptide or a peptidomimetic may include the steps of: (j) remove the protecting group from the third amino acid (AA3); (k) provide a fourth amino acid (AA4); and (l) couple the fourth amino acid (AA4) to the third amino acid to form a peptide bond between the fourth amino acid (AA4) and the third amino acid (I-AA1-AA2-AA3-AA4).

[343] In one embodiment, step (l) comprises coupling the carboxylic acid moiety of AA4 with the amino moiety of AA3.

[344] In one embodiment, the fourth amino acid (AA4) is NHFmoc or NHFmoc

[345] In some embodiments, the method of producing a peptide or peptidomimetic may include the steps of: (m) remove the protecting group from the fourth amino acid (AA4); (n) provide a fifth amino acid (AA5); and (o) couple the fifth amino acid (AA5) to the fourth amino acid to form a peptide bond between the fifth amino acid (AA5) and the fourth amino acid (I-AA1-AA2-AA3-AA4-AA5).

[346] In one embodiment, step (o) comprises coupling the carboxylic acid moiety of AA5 with the amino moiety of AA4.

[347] In one embodiment, the fifth amino acid (AA5) is NHFmoc or NHFmoc

[348] In some embodiments, the method of producing a peptide or a peptidomimetic may include the steps of: (p) remove the protecting group from the fifth amino acid (AA5); (q) provide a sixth amino acid (AA6); and (r) couple the sixth amino acid (AA6) to the fifth amino acid Petition 870260086043, dated 08 / 24 / 2026, page 92 / 389 87 / 328 to form a peptide bond between the sixth amino acid (AA6) and the fifth amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6).

[349] In one embodiment, step (r) comprises coupling the carboxylic acid moiety of AA6 with the amino moiety of AA5.

[350] In one embodiment, the sixth amino acid (AA6) is NHFmoc

[351] In some embodiments, the method of producing a peptide or a peptidomimetic may include the steps of: (s) remove the protecting group from the sixth amino acid (AA6); (t) provide a seventh amino acid (AA7); and (u) couple the seventh amino acid (AA6) to the sixth amino acid to form a peptide bond between the seventh amino acid (AA7) and the sixth amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6-AA7).

[352] In one embodiment, step (u) comprises coupling the carboxylic acid moiety of AA7 with the amino moiety of AA6.

[353] In one embodiment, the seventh amino acid (AA7) is gr oh NHFmoc or NHFmoc

[354] In some embodiments, the method of producing a peptide or a peptidomimetic may include the steps of: (v) remove the protecting group from the seventh amino acid (AA7); (w) provide an eighth amino acid (AA8); and (x) couple the eighth amino acid (AA8) to the seventh amino acid to form a peptide bond between the eighth amino acid (AA8) and the seventh amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6-AA7-AA8).

[355] In one embodiment, step (x) comprises coupling the carboxylic acid moiety of AA8 with the amino moiety of AA7.

[356] In one embodiment, the eighth amino acid (AA8) is FmocHN OH

[357] In some forms, the production method of a Petition 870260086043, dated 08 / 24 / 2026, page 93 / 389 88 / 328 peptide or peptidomimetic may include the following steps: (y) remove the protecting group from the eighth amino acid (AA8); (z) provide a ninth amino acid (AA9); and (aa) couple the ninth amino acid (AA9) to the eighth amino acid to form a peptide bond between the ninth amino acid (AA9) and the eighth amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6-AA7-AA8-AA9).

[358] In one embodiment, the (aa) step comprises the coupling of the carboxylic acid moiety of AA9 with the amino moiety of AA8. h ? N TT^0H

[359] In one embodiment, the ninth amino acid (AA9) is N'N NHFmocou NHFmoc

[360] In some embodiments, the method of producing a peptide or peptidomimetic may include the steps of: (bb) remove the protecting group from the ninth amino acid (AA9); (cc) provide a tenth amino acid (AA10); and (dd) couple the tenth amino acid (AA10) to the ninth amino acid to form a peptide bond between the tenth amino acid (AA10) and the ninth amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6-AA7-AA8-AA9-AA10).

[361] In one embodiment, step (dd) comprises coupling the carboxylic acid moiety of AA10 with the amino moiety of AA9.

[362] In one embodiment, the tenth amino acid (AA10) is.

[363] In some embodiments, the method of producing a peptide or peptidomimetic may include the steps of: repeating the steps of (i) removing the amino acid protecting group (AAn); Petition 870260086043, dated 08 / 24 / 2026, p. 94 / 389 89 / 328 (ii) provide a successor amino acid (AAn+i); and (iii) couple the successor amino acid (AAn+i) to the amino acid (AAn) to form a peptide bond between the successor amino acid (AAn+i) and the amino acid (AAn), wherein said repetition may be carried out from 1 to 100 times.

[364] In some embodiments, the method of producing a peptide or peptidomimetic may include the steps of: (ee) remove the protecting group from the tenth amino acid (AA10); (ff) provide a compound of Formula (B): BocHN where x is an integer from 1 to 15; and (gg) couple the compound of Formula (B) to one of the amino acids in the peptide or peptidomimetic to form a triazole ring.

[365] In one embodiment, the compound of Formula (B) has the following Formula: BocHN O

[366] In some embodiments of the present disclosure, one or more peptides may be linked to the amino acid (AAn). For example, in some embodiments, the method of producing a peptide or a peptidomimetic may include the steps of: repeat the steps of (i) removing the protecting group from the amino acid (AAn); (ii) provide a peptide (AAm-AAmp), where p is from 2 to 20; and (iii) couple the amino acid in the peptide (AAmi-AAmp) to the amino acid (AAn) to form a peptide bond between the amino acid in the peptide (AAmi-AAmp) and the amino acid (AAn), wherein said repetition may be carried out from 1 to 100 times.

[367] According to the present development, in the peptide (AAmiAAmp) m can be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. In some embodiments, m is 2, 3, 4, 5, 6, Petition 870260086043, dated 08 / 24 / 2026, p. 95 / 389 90 / 328 7, 8, 9, 10, 11, 12, 13, 14 or 15. In some modalities, m is 2, 3, 4, 5, 6, 7, 8, 9 or 10.

[368] According to the present disclosure, the peptide (AAm1 - AAmp) can be a dipeptide, tripeptide, tetrapeptide, pentapeptide, hexapeptide, heptapeptide, octapeptide, nonapeptide, or decapeptide.

[369] Peptides may include all D-amino acids, all L-amino acids, or a mixture of L-amino acids and D-amino acids. In preferred embodiments, the peptide includes only D-amino acids or a mixture of D-amino acids and L-amino acids, where the D-amino acid content is greater than 50%, 60%, 70%, 80%, 90%, or 95%.

[370] During synthesis, carboxylic acids or amines not participating in the reacting pool of amino acids or peptide fragments may be protected by a suitable protecting group (PG), which may be selectively removed later if desired. A detailed description of these groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Editors, Academic Press, New York, 1981, which is incorporated herein by reference in its entirety.

[371] In some embodiments, the method of producing a peptide or a peptidomimetic according to any of the above embodiments further comprises: (hh) cleave the peptide bond between the first amino acid (AA1) and the compound of Formula (I) to obtain the peptide or peptidomimetic.

[372] According to the present disclosure, each of the first amino acid (AA1), the second amino acid (AA2), the third amino acid (AA3), the fourth amino acid (AA4), the fifth amino acid (AA5), the sixth amino acid (AA6), the seventh amino acid (AA7), the eighth amino acid (AA8), the ninth amino acid (AA9), the tenth amino acid (AA10) and the successor amino acid (AAn+1) can be selected independently of the group that Petition 870260086043, dated 08 / 24 / 2026, p. 96 / 389 91 / 328 consists of NN' nn OH NH-PG5,PG5 No N H OH where PG5 is a suitable protective group.

[373] According to the present disclosure, any suitable protecting group that can be used on amino acids can be used as suitable groups that can be used to protect the amino group. PG5. Protecting groups known to those skilled in the art. A detailed description of these groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Press, New York, 1981, which is incorporated herein by reference in its entirety. For example, PG5 can be selected independently at each occurrence of the group consisting of triphenylmethyl (Trt), allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc). Petition 870260086043, dated 08 / 24 / 2026, page 97 / 389 92 / 328

[374] According to the present disclosure, each of the first amino acid (AA1), the second amino acid (AA2), the third amino acid (AA3), the fourth amino acid (AA4), the fifth amino acid (AA5), the sixth amino acid (AA6), the seventh amino acid (AA7), the eighth amino acid (AA8), the ninth amino acid (AA9), the tenth amino acid (AA10) and the successor amino acid (AAn+1) can be selected independently of the group that NHFmoc

[375] In one embodiment, the peptidomimetic has a Formula: Petition 870260086043, dated 08 / 24 / 2026, p. 98 / 389 93 / 328 a salt of the same. There is a formula:

[376] In one modality the peptidomimetic or a salt of it.

[377] According to the present disclosure, amino acids that can be used to prepare peptides and peptidomimetics can be natural and non-natural amino acids.

[378] The present disclosure provides a method for preparing a compound of Formula (DI): in which: k is an integer from 1 to 15; q is an integer from 0 to 10; R1dé C1-6 alkyl; PG6 is a suitable protective group; and PG7 is a suitable protective group, or a salt thereof. This method includes: (a) provide a compound of Formula (DII) with the structure: Petition 870260086043, dated 08 / 24 / 2026, p. 99 / 389 94 / 328 (b) to form the compound of Formula (DI) from the compound of Formula (DII).

[379] According to the present disclosure, PG6 is any suitable protecting group that can be used to protect the amino group. Suitable protecting groups that can be used are known to those skilled in the art. A detailed description of these groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Press, New York, 1981, which is incorporated herein by reference in its entirety. For example, PG6 can be selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc), and 9-fluorenylmethoxycarbonyl (Fmoc). In some embodiments, PG6 is 9-fluorenylmethoxycarbonyl (Fmoc).

[380] According to the present disclosure, PG7 is any suitable protecting group that can be used to protect the amino group. Suitable protecting groups that can be used are known to those skilled in the art. A detailed description of such groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Press, New York, 1981, which is incorporated herein by reference in its entirety. For example, PG7 can be selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc), and 9-fluorenylmethoxycarbonyl (Fmoc). In some embodiments, PG7 is tert-butyloxycarbonyl (Boc).

[381] In one form, the compound of Formula (DI) has the Petition 870260086043, dated 08 / 24 / 2026, p. 100 / 389 95 / 328

[382] In another embodiment, the compound of Formula (DII) has the structure of Formula (DIIa) or Formula (DIIb):

[383] In some embodiments, step (b) of forming the compound of Formula (DI) comprises: react the compound of Formula (DII) with a compound of Formula (DIII): (DIII), to produce the compound of Formula (II). Petition 870260086043, dated 08 / 24 / 2026, p. 101 / 389 96 / 328

[384] In one embodiment, the compound of Formula (DIII) has the structure of Formula (DIIIa): (DIIIa).

[385] In some embodiments, the process for preparing a Formula (DI) compound may include the step of: provide a compound of Formula (DIV) with the structure: (DIV) or a salt thereof; and form the compound of Formula (DII) from the compound of Formula (DIV) before step (a).

[386] In one embodiment, the compound of Formula (DIV) has the structure of Formula (DIVa) or Formula (DIVb):

[387] In some embodiments, the compound formation step of Formula (DII) comprises: react the compound of Formula (DIV) with a compound of Formula (DVa) or Formula (DVb): PG6-X (DVa) or PG62O (DVb), Petition 870260086043, dated 08 / 24 / 2026, p. 102 / 389 97 / 328 in which X is OSu, OTf, Cl, or Br; to produce the compound of Formula (DII).

[388] According to the present disclosure, the compound of Formula (DVa) or Formula (DVb) can be selected from the group consisting of AllocCl, Alloc2O, Cbz2O, CbzCl, FmocCl, FmocOSu and Boc2O.

[389] In some embodiments, the process for preparing a Formula (DI) compound may include the step of: provide a Formula (DVI) compound with the following structure: starting from the compound of Formula (DVI).

[390] In some forms, the compound formation step of Formula (DIV) comprises: react the compound of Formula (DVI) with a protecting group removing agent to produce the compound of Formula (DIV).

[391] According to the present disclosure, any suitable protecting group scavenging agent can be used to remove the PG8 protecting group from the amino group of the compound of Formula (DVI). Suitable protecting group scavenging agents that can be used to remove a specific protecting group are known to those skilled in the art. A detailed description of such groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Press, New York, 1981, which is incorporated herein by reference in its entirety. For example, the protecting group scavenging agent can be selected from the group consisting of Pd(PPh)3, PhSiH3, H2, HCl, Petition 870260086043, dated 08 / 24 / 2026, page 103 / 389 98 / 328 piperidine and trifluoroacetic acid (TFA).

[392] In one embodiment, the Formula (DVI) compound has the structure of Formula (DVIa) or Formula (DVIb):

[393] In some embodiments, the process for preparing a Formula (DI) compound may include the step of: provide a compound of Formula (DVII) with the structure: (DVII form the compound of Formula (DVI) from the compound of Formula (DVII).

[394] In some forms, the Formula compound formation step (DVI) comprises: react the compound of Formula (DVII) with a base to produce the compound of Formula (DVI).

[395] According to the present disclosure, any suitable base can be used to hydrolyze the methyl ester group in the compound of Formula (DVII). In some embodiments, the base is selected from the group consisting of LiOH, NaOH and KOH. Petition 870260086043, dated 08 / 24 / 2026, p. 104 / 389 99 / 328

[396] In one embodiment, the compound of Formula (DVII) has the structure of Formula (DVIIa) or Formula (DVIIb):

[397] In some embodiments, the process for preparing a Formula (DI) compound may include the step of: provide a compound of Formula (DVIII) with the structure: in which LG' is a suitable life group; and form the compound of Formula (DVII) from the compound of Formula (DVIII).

[398] In some embodiments, the compound formation step of Formula (DVII) comprises: react the compound of Formula (DVIII) with an azide group introducing agent to produce the compound of Formula (DVII).

[399] The azide group introducing agent that can be used to perform the above embodiment is known as Petition 870260086043, dated 08 / 24 / 2026, p. 105 / 389 100 / 328 technicians in the subject. In one embodiment, the azide group introducing agent is selected from the group consisting of NaN3, TMSN3, (PhO)2P(O)N3, Zn(N3)2*2Py and n-Bu4NN3.

[400] In one embodiment, LG' is selected from the group consisting of halogen, OTf, OMs and OTs.

[401] In another embodiment, the compound of Formula (DVIII) has the structure of Formula (DVIIIa) or Formula (DVIIIb):

[402] In some embodiments, the process for preparing a Formula (DI) compound may include the step of: provide a compound of Formula (DIX) with the structure: (DIX), in which LG'' is a suitable life group; and form the compound of Formula (DVIII) from the compound of Formula (DIX).

[403] In one embodiment, LG'' is selected from the group consisting of halogen, OTf, OMs and OTs.

[404] In one embodiment, the compound formation step of Formula (DVIII) comprises: react the compound of Formula (DIX) with a compound of Formula Petition 870260086043, dated 08 / 24 / 2026, p. 106 / 389 101 / 328 (DX): in which PG8 is a suitable protective group; to produce the compound of Formula (DVII).

[405] According to the present disclosure, PG8 is any suitable protecting group that can be used to protect the amino group. Suitable protecting groups that can be used are known to those skilled in the art. A detailed description of such groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Press, New York, 1981, which is incorporated herein by reference in its entirety. For example, PG8 can be selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc), and 9-fluorenylmethoxycarbonyl (Fmoc). In some embodiments, PG8 is tert-butyloxycarbonyl (Boc).

[406] In another embodiment, Formula structure (DIXa):

[407] In another embodiment, Formula structure (DXa): the Formula compound (DIX) has the Br or Z (DIXa). the Formula compound (DX) has the Petition 870260086043, dated 08 / 24 / 2026, p. 107 / 389 102 / 328

[408] In some embodiments, the process for preparing a Formula (DI) compound may include the steps of: provide a compound with the formula (DXI) and the structure: (DXI), in which R2dé C1-6 alkylene; and form the compound of Formula (DIX) from the compound of Formula (DXI).

[409] In some embodiments, the compound formation step of Formula (DIX) comprises the reaction of the compound of Formula (DXI) with a reducing agent to produce the compound of Formula (DIX).

[410] According to the present disclosure, any reducing agent capable of reducing the alkene double bond can be used to prepare the compound of Formula (DIX). In some embodiments, the reducing agent is selected from the group consisting of H2, NH4HCO2, NABH(OAc)3 and LiAlH4.

[411] In one embodiment, the compound of Formula (DXI) has the structure of Formula (DXIa): Br0(DXIa).

[412] In some embodiments, the process for preparing a compound of Formula (DI) may include the steps of: providing a compound of Formula (DXII) with the structure: Petition 870260086043, dated 08 / 24 / 2026, p. 108 / 389 103 / 328 ( (DXII), and form the compound of Formula (DXI) from the compound of Formula (DXII).

[413] In some embodiments, the compound formation step of Formula (DXI) comprises: react the compound of Formula (DXII) with a compound of Formula (DXIII): PPh3*C1-6alkyl-Hal (DXIII), where Hal is halogen, to produce the compound of Formula (DXI).

[414] In one embodiment, the compound of Formula (DXII) has the structure of Formula (DXIIa): (DXIIa).

[415] In another embodiment, the compound of Formula (DXIII) has the structure of Formula (DXIIIa): PPh3*MeBr (DXIIIa).

[416] In some embodiments, the process for preparing a Formula (DI) compound may include the steps of: provide a compound of Formula (DXIV) with the structure: O (DXIV), and form the compound of Formula (DXII) from the compound of Formula (DXIV).

[417] In some embodiments, the compound formation step of Formula (DXII) comprises: react the compound of Formula (DXIV) with a compound of Formula (DXV): Petition 870260086043, dated 08 / 24 / 2026, p. 109 / 389 104 / 328 (DXV), in which LG' is a suitable co-existence group, to produce the compound of Formula (DXII).

[418] In one embodiment, LG' is selected from the group consisting of halogen, OTf, OMs and OTs.

[419] In another embodiment, the compound of Formula (DXIV) has the structure of Formula (DXIVa): ILh HO o (DXIVa).

[420] In some embodiments, the process for preparing a Formula (DI) compound may include the steps of: provide a compound of Formula (DXVI) with the structure: PG8O । II HN,, X ·< OMe XX LG* (DXVI), where LG* is a suitable cohabiting group, form the compound of Formula (DX) from the compound of Formula (DXVI).

[421] In one embodiment, LG* is selected from the group consisting of halogens, OTf, OMs and OTs.

[422] In some forms, the compound formation step of Formula (DX) comprises: react the compound of Formula (DXVI) with a compound of Formula (DXVII): Petition 870260086043, dated 08 / 24 / 2026, p. 110 / 389 105 / 328 O \ / I o I (DXVII), to produce the compound of Formula (DX).

[423] In one embodiment, the compound of Formula (DXVI) has the structure of Formula (DXVIc): Boc O HN,, A ·< OMe Xj OTf (DXVIc).

[424] In some embodiments, the process for preparing a Formula (DI) compound may include the steps of: provide a compound of Formula (DXVIII) with the structure: PG8O I II HN,, X ·< OMe XX OH (DXVIII), and form the compound of Formula (DXVI) from the compound of Formula (DXVIII).

[425] In some forms, the compound formation step of Formula (DXVI) comprises: react the compound of Formula (DXVIII) with a compound of Formula (DXIXa) or Formula (DXIXb): LG*-X (DXIXa) or LG*2O (DXIXb), where X is OSu, Cl, or Br; to produce the compound of Formula (DXVI).

[426] In one embodiment, the compound of Formula (DXIXa) or Formula (DXIXb) is selected from the group consisting of TfCl, Tf2O, MsCl and Ms2O. Petition 870260086043, dated 08 / 24 / 2026, p. 111 / 389 106 / 328

[427] The present disclosure provides a method for preparing a compound of Formula (DII): in which: q is an integer from 0 to 10; R1dé C1-6 alkyl; e PG6 is a suitable protecting group, or a salt thereof, the said process comprising: (a) providing a compound of Formula (DXXI) with the structure: (DXXI) or a salt thereof, (b) form the compound of Formula (DII) from the compound of Formula (DXXI).

[428] In some embodiments, PG6 is selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

[429] In some forms, the compound Formula (DXXI) is O / VY^OH NHFmoc treated with compound1.

[430] In some embodiments, the compound of Formula (DXXI) is treated with a catalyst. In some embodiments, the catalyst is Pd(dppf)Cl2-DCM.

[431] In some embodiments, the compound of Formula (DXXI) is treated with a base. In some embodiments, the base is K2CO3. Petition 870260086043, dated 08 / 24 / 2026, p. 112 / 389 107 / 328

[432] In some embodiments, the preparation is carried out in a solvent mixture composed of H2O / iPrOH.

[433] In some embodiments, the compound of Formula (DII) has the structure of Formula (DIIa) or Formula (DIIb): FmocHN,, OH (DIIa), FmocHN,, OH N3. O (DIIb).

[434] In some forms, the Formula compound (DXXI) is formed by exposure HO R1d

[435] In some embodiments, the compound of Formula (DXXI) is formed in the presence of PPh3

[436] In some embodiments, the Formula (DXXI) compound is formed in the presence of DIAD.

[437] In some embodiments, the compound of Formula (DXXI) is formed in the presence of 4Å molecular sieves.

[438] In some embodiments, the compound of Formula (DXXI) is formed in an organic solvent. In some embodiments, the organic solvent is THF.

[439] In some forms, R1dé formed by Petition 870260086043, dated 08 / 24 / 2026, p. 113 / 389 108 / 328 exposureHθ Br R1d PBin, 2.

[440] In some modalities HO O i B- R1dformed in the presence of Pd(OAc)

[441] In some modalities HO O i B- R1dformed in the presence of PCy3.

[442] In some modalities HO O i B- R1dformed in the presence of KOAc.

[443] In some modalities HO O i B- R1d formed in the presence of dioxane.

[444] In some modalities, HO i B. R1dformed at an elevated temperature for a period of time.

[445] In some forms HO Br R1dé formed by the exhibition Hθ R1da Bu4N+Br3 Petition 870260086043, dated 08 / 24 / 2026, p. 114 / 389 109 / 328

[446] In some forms, Br R1 is formed in an organic solvent. In some embodiments, the organic solvent is a mixture of DCM and methanol.

[447] The present disclosure provides a method for preparing a compound of Formula (DII): in which: q is an integer from 0 to 10; R1dé C1-6 alkyl; e PG6 is a suitable protecting group, or a salt thereof, the said process comprising: (a) providing a compound of Formula (DIV) with the structure: from the same, (b) form the compound of Formula (DII) from the compound of Formula (DIV).

[448] According to the present disclosure, PG6 is any suitable protecting group that can be used to protect the amino group. Suitable protecting groups that can be used are known to those skilled in the art. A detailed description of these groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Petition 870260086043, dated 08 / 24 / 2026, p. 115 / 389 110 / 328 Press, New York, 1981, which is incorporated herein by reference in its entirety. For example, PG6 may be selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc), and 9-fluorenylmethoxycarbonyl (Fmoc). In some embodiments, PG6 is 9-fluorenylmethoxycarbonyl (Fmoc).

[449] In one embodiment, the compound of Formula (DII) has the structure of Formula (DIIa) or Formula (DIIb):

[450] In another embodiment, the compound of Formula (DIV) has the structure of Formula (DIVa) or Formula (DIVb): Petition 870260086043, dated 08 / 24 / 2026, p. 116 / 389 111 / 328

[451] In some embodiments, the process of forming the compound of Formula (DII) comprises: react the compound of Formula (DIV) with a compound of Formula (DVa) or Formula (DVb): PG6-X (DVa) or PG62O (DVb), where X is OSu, OTf, Cl, or Br; to produce the compound of Formula (DII).

[452] According to the present disclosure, the compound of Formula (DVa) or Formula (DVb) is selected from the group consisting of AllocCl, Alloc2O, Cbz2O, CbzCl, FmocCl, FmocOSu and Boc2O.

[453] In some embodiments, the process for preparing a Formula (DII) compound may include the steps of: provide a compound of Formula (DXVI) with the structure: OC1-6 alkyl (DXVI) in which PG8 is a suitable protecting group; and form the compound of Formula (DIV) from the compound of Formula (DXVI).

[454] According to the present disclosure, PG8 is any suitable protecting group that can be used to protect the amino group. Suitable protecting groups that can be used are known to those skilled in the art. A detailed description of such groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Press, New York, 1981, which is incorporated herein by reference in its entirety. For example, PG8 can be selected from the group Petition 870260086043, dated 08 / 24 / 2026, p. 117 / 389 112 / 328 which consists of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc). In some embodiments, PG8 is tert-butyloxycarbonyl (Boc).

[455] In some embodiments, the compound formation step of Formula (DIV) comprises the reaction of compound Formula (DXVI) with a protecting group removing agent to produce compound Formula (DIV).

[456] According to the present disclosure, any suitable shielding agent can be used to remove the PG8 shielding group from the amino group of the compound of Formula (DVI). Suitable shielding agents that can be used to remove a specific shielding group are known to those skilled in the art. A detailed description of such groups, their selection and chemical composition is contained in The Peptides, Vol. 3, Gross and Meinenhofer, Eds., Academic Press, New York, 1981, which is incorporated herein by reference in its entirety. In some embodiments, the shielding agent is selected from the group consisting of HCl, Pd(PPh)3, PhSiH3, H2, piperidine and trifluoroacetic acid (TFA).

[457] In one embodiment, the compound of Formula (DXVI) has the structure of Formula (DXVIa) or Formula (DXVIb): Petition 870260086043, dated 08 / 24 / 2026, p. 118 / 389 113 / 328

[458] In some embodiments, the process for preparing a Formula (DII) compound may include the steps of: provide a compound of Formula (DXVII) with the structure: in which LG' is a suitable life group; and form the compound of Formula (DXVI) from the compound of Formula (DXVII).

[459] In some embodiments, the compound formation step of Formula (DXVI) comprises the reaction of the compound of Formula (DXVII) with an azide group introducing agent to produce the compound of Formula (DXVI).

[460] In some embodiments, the azide group introducing agent is selected from the group consisting of NaN3, TMSN3, (PhO)2P(O)N3, Zn(N3)2*2Py and n-Bu4NN3.

[461] In some embodiments, LG' is selected from the group consisting of halogen, OTf, OMs and OTs.

[462] In one embodiment, the compound of Formula (DXVII) has the structure of Formula (DXVIIa) or Formula (DXVIIb): Petition 870260086043, dated 08 / 24 / 2026, p. 119 / 389 114 / 328 (DXVIIb).

[463] In some embodiments, the process for preparing a Formula (DII) compound may include the steps of: provide a compound of Formula (DIX) with the structure: (DIX), in which LG'' is a suitable life group; and form the compound of Formula (DXVII) from the compound of Formula (DIX).

[464] In some embodiments, LG'' is selected from the group consisting of halogen, OTf, OMs and OTs.

[465] In some embodiments, the compound formation step of Formula (DXVII) comprises: react the compound of Formula (DIX) with a compound of Formula (DXVIII): to produce the compound of Formula (DXVII).

[466] In one embodiment, the compound of Formula (DIX) has the structure of Formula (DIXa): (DIXa) Petition 870260086043, dated 08 / 24 / 2026, p. 120 / 389 115 / 328

[467] In another embodiment, the compound of Formula (DXVIII) has the structure of Formula (DXVIIIa):

[468] In some embodiments, the process for preparing a compound of Formula (DII) may include the steps of: providing a compound of Formula (DXIX) with the structure: x^LG (Dxix), and form the compound of Formula (DIX) from the compound of Formula (DXIX).

[469] In some embodiments, the step of forming the compound of Formula (DIX) comprises: reacting the compound of Formula (DXIX) with a compound of Formula (DXV): LG5 Vj LG''V'A (DXV), where LG' is a suitable co-existence group, to produce the compound of Formula (DXIX).

[470] In one embodiment, LG' is selected from the group consisting of halogen, OTf, OMs and OTs.

[471] In another embodiment, the compound of Formula (DXIX) has the structure of Formula (DXIXa): ^Br HO^'xO^'''·''^ (DXIXa).

[472] In another embodiment, the compound of Formula (DXV) has the structure of Formula (DXVa): Petition 870260086043, dated 08 / 24 / 2026, p. 121 / 389 116 / 328 (DXVa).

[473] In some embodiments, the process for preparing a Formula (DII) compound may include the steps of: provide a compound with formula (DXX) and the following structure: n (DXX), and form the compound of Formula (DXIX) from the compound of Formula (DXX).

[474] In some embodiments, the step of forming the Formula (DXIX) compound comprises: react the compound of Formula (DXX) with an introducing agent LG” to produce the compound of Formula (DXIX).

[475] In one embodiment, the introducing agent LG” is NBu4Br3.

[476] In another embodiment, the compound of Formula (DXX) has the structure of Formula (DXXa): (DXXa). Therapeutic formulations, Administration and Uses

[477] The present disclosure provides pharmaceutical compositions comprising the peptidomimetic or compound of the present disclosure.

[478] The compositions of the present disclosure may be formulated with suitable carriers, excipients, and other agents that provide enhanced transfer, administration, tolerability, and the like. A multitude of suitable formulations may be found in the formulary known to all pharmaceutical chemists: Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, PA. These formulations include, for example, powders, pastes, ointments, gels, waxes, oils, lipids, lipid-containing vesicles (cationic or anionic) (such as LIPOFECTIN™, Life Technologies, Carlsbad, CA), DNA conjugates, anhydrous absorption pastes, Petition 870260086043, dated 08 / 24 / 2026, page 122 / 389 117 / 328 oil-in-water and water-in-oil emulsions, carbowax emulsions (polyethylene glycols of various molecular weights), semi-solid gels and semi-solid mixtures containing carbowax. See also Powell et al. Compendium of excipients for parenteral formulations PDA (1998) J Pharm Sci Technol 52:238-311.

[479] The dose of a peptidomimetic or compound administered to a patient may vary depending on the patient’s age and size, the target disease, conditions, route of administration, and similar factors. The appropriate dose is typically calculated based on body weight or body surface area. When a peptidomimetic or compound of the present disclosure is used for therapeutic purposes in an adult patient, it may be advantageous to administer the peptidomimetic or compound of the present disclosure intravenously, typically in a single dose of about 0.01 to about 20 mg / kg of body weight, more preferably about 0.02 to about 7, about 0.03 to about 5, or about 0.05 to about 3 mg / kg of body weight. Depending on the severity of the condition, the frequency and duration of treatment may be adjusted.Effective dosages and regimens for the administration of a peptidomimetic or compound can be determined empirically; for example, patient progress can be monitored by periodic assessments and the dose adjusted accordingly. Furthermore, interspecific dose escalation can be performed using methods well-known in the art (e.g., Mordenti et al., 1991). Pharmaceut. Res. 8:1351).

[480] Several delivery systems are known and can be used to administer the developing pharmaceutical composition, for example, encapsulation in liposomes, microparticles, microcapsules, recombinant cells capable of expressing mutant viruses, receptor-mediated endocytosis (see, for example, Wu et al., 1987, J. Biol. Chem. 262:4429- 4432). Introduction methods include, but are not limited to Petition 870260086043, dated 08 / 24 / 2026, page 123 / 389 118 / 328 a, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural and oral routes. The composition can be administered by any convenient route, for example, by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.) and can be administered together with other biologically active agents. Administration can be systemic or local.

[481] A pharmaceutical composition of the present invention can be administered subcutaneously or intravenously with a standard needle and syringe. Furthermore, with respect to subcutaneous administration, a pen-based administration device has immediate applications in administering a pharmaceutical composition of the present disclosure. Such a pen-based administration device can be reusable or disposable. A reusable pen-based administration device generally uses a replaceable cartridge containing a pharmaceutical composition. Once all the pharmaceutical composition within the cartridge has been administered and the cartridge is empty, the empty cartridge can be easily discarded and replaced with a new cartridge containing the pharmaceutical composition. The pen-based administration device can then be reused. In a disposable pen-based administration device, there is no replaceable cartridge.Instead, the disposable pen-type administration device comes pre-filled with the pharmaceutical composition held in a reservoir inside the device. Once the reservoir is empty of the pharmaceutical composition, the entire device is discarded.

[482] Various reusable pen and autoinjector delivery devices have applications in the subcutaneous administration of a pharmaceutical composition of the present disclosure. Examples include, but are not limited to, AUTOPEN™ (Owen Mumford, Inc., Petition 870260086043, dated 08 / 24 / 2026, page 124 / 389 119 / 328 Woodstock, United Kingdom), DISETRONIC™ pen (Disetronic Medical Systems, Bergdorf, Switzerland), HUMALOG MIX 75 / 25™ pen, HUMALOG™ pen, HUMALIN 70 / 30™ pen (Eli Lilly and Co., Indianapolis, IN), NOVOPEN™ I, II and III (Novo Nordisk, Examples of disposable pen delivery devices with applications in the subcutaneous administration of a pharmaceutical composition of the present disclosure include, but are not limited to, the SOLOSTAR™ pen (sanofi-aventis), the FLEXPEN™ (Novo Nordisk) and the KWIKPEN™ (Eli Lilly), the autoinjector. Examples of disposable pen delivery devices with applications in the subcutaneous administration of a pharmaceutical composition of the present disclosure include, but are not limited to, the SOLOSTAR™ pen (sanofi-aventis), the FLEXPEN™ (Novo Nordisk) and the KWIKPEN™ (Eli Lilly) autoinjector. SURECLICK™ (Amgen, Thousand Oaks, CA), the PENLET™ (Haselmeier, Stuttgart, Germany), the EPIPEN (Dey, LP), and the HUMIRA™ pen (Abbott Labs, Abbott Park, IL), to name just a few.

[483] In certain situations, the pharmaceutical composition can be administered in a controlled-release system. In one embodiment, a pump may be used (see Langer, supra; Sefton, 1987, CRC Crit. Ref. Biomed. Eng. 14:201). In another embodiment, polymeric materials may be used; see Medical Applications of Controlled Release, Langer and Wise (eds.), 1974, CRC Pres., Boca Raton, Florida. In yet another embodiment, a controlled-release system may be placed close to the target of the composition, thus requiring only a fraction of the systemic dose (see, for example, Goodson, 1984, in Medical Applications of Controlled Release, supra, vol. 2, pp. 115-138). Other controlled-release systems are discussed in the review by Langer, 1990, Science 249:1527-1533.

[484] Injectable preparations may include pharmaceutical forms for intravenous, subcutaneous, intracutaneous and intramuscular injections, drip infusions, etc. These injectable preparations may be prepared by methods Petition 870260086043, dated 08 / 24 / 2026, page 125 / 389 120 / 328 publicly known. For example, injectable preparations can be prepared, for example, by dissolving, suspending or emulsifying the antibody or its salt described above in a sterile aqueous medium or in an oily medium conventionally used for injections. As an aqueous medium for injections, there are, for example, physiological saline, an isotonic solution containing glucose and other auxiliary agents, etc., which can be used in combination with an appropriate solubilizing agent, such as an alcohol (e.g., ethanol), a polyalcohol (e.g., propylene glycol, polyethylene glycol), a non-ionic surfactant [e.g., polysorbate 80, HCO-50 (polyoxyethylene (50 mol) adduct of hydrogenated castor oil)], etc. As an oily medium, sesame oil, soybean oil, etc., are employed, which can be used in combination with a solubilizing agent, such as benzyl benzoate, benzyl alcohol, etc.The injection, prepared in this way, is preferably placed in an appropriate ampoule.

[485] Advantageously, the pharmaceutical compositions for oral or parenteral use described above are prepared in unit dose pharmaceutical forms suitable to accommodate the dose of the active ingredients. Such unit dose pharmaceutical forms include, for example, tablets, pills, capsules, injections (ampoules), suppositories, etc. The amount of the aforementioned antibody contained is generally from about 5 to about 500 mg per unit dose pharmaceutical form; especially in the injectable form, it is preferable that the aforementioned antibody be contained in about 5 to about 100 mg and in about 10 to about 250 mg for the other pharmaceutical forms. Therapeutic uses of peptidomimetics or compounds

[486] In another aspect, the peptidomimetics or compounds (e.g., GLP1 peptidomimetics) disclosed herein are useful, inter alia, for the treatment, prevention and / or improvement of a disease, disorder or condition that requires such treatment.

[487] In one respect, the present revelation provides a method Petition 870260086043, dated 08 / 24 / 2026, p. 126 / 389 121 / 328 treatment of a condition in an individual requiring the same comprising administering to the individual a therapeutically effective amount of a peptidomimetic or compound (e.g., GLP1 peptidomimetic) according to the disclosure, or the composition comprising any compound according to the present disclosure.

[488] In some embodiments, the peptidomimetics or compounds (e.g., GLP1 peptidomimetics) disclosed herein are useful for treating any disease or disorder in which stimulation, activation, and / or targeting of GLP1R is beneficial. In particular, the compounds of the present disclosure may be used for the treatment, prevention, and / or improvement of any disease or disorder associated with or mediated by the expression or activity of GLP1R.

[489] In some embodiments, the peptidomimetics or compounds (e.g., GLP1 peptidomimetics) disclosed herein are useful for the treatment of a GLP1R-associated condition. In some embodiments, the GLP1R-associated condition is type 1 or type 2 diabetes mellitus. The administered peptidomimetic or compound (e.g., GLP1 peptidomimetic) may cause at least one of the following outcomes: induction of insulin secretion, suppression of glucagon release, reduction of blood glucose, improvement of glycemic control, promotion of islet neogenesis, and delayed gastric emptying or potentiation of glucose-resistant islets.

[490] In some forms, the condition associated with GLP1R is a neurodegenerative disorder, a cognitive disorder, a memory disorder, or a learning disorder. The neurodegenerative disorder may be, for example, dementia, senile dementia, mild cognitive impairment, Alzheimer's-related dementia, Huntington's disease, tardive dyskinesia, hyperkinesias, mania, Parkinson's syndrome, SteelRichard syndrome, Down syndrome, myasthenia gravis, trauma Petition 870260086043, dated 08 / 24 / 2026, page 127 / 389 122 / 328 cranial, traumatic brain injury, vascular amyloidosis, type I cerebral hemorrhage with amyloidosis, brain inflammation, Friedreich's ataxia, acute confusional disorder, amyotrophic lateral sclerosis, glaucoma, and Alzheimer's disease.

[491] In some forms, the condition associated with GLP1R is liver disease. Liver disease may be, for example, non-alcoholic fatty liver disease (NAFLD), hepatic steatosis, non-alcoholic steatohepatitis (NASH), and cirrhosis.

[492] In some modalities, the condition associated with GLP1R is coronary artery disease. Coronary artery disease can be, for example, cardiomyopathy and myocardial infarction.

[493] In some modalities, the condition associated with GLP1R is kidney disease. Kidney disease can be, for example, hypertension or chronic renal failure.

[494] In some forms, the condition associated with GLP1R is an eating disorder. The eating disorder may be, for example, binge eating disorder.

[495] Without intending to be limited by theory, the peptidomimetics or compounds (e.g., GLP1 peptidomimetics) disclosed here may be employed to attenuate the effects of apoptosis-mediated degenerative diseases of the central nervous system, such as Alzheimer's disease, Creutzfeldt-Jakob disease and bovine spongiform encephalopathy, chronic wasting syndrome and other prion-mediated apoptotic neural diseases (see, for example, Perry and Grieg (2004) Current Drug Targets 6:565-571). The administration of a peptidomimetic or compound (e.g., GLP1 peptidomimetic) disclosed here may also lead to negative modulation of βAP and thus improve pathologies mediated by mono- or oligomers of Αβ associated with Alzheimer's disease (see, for example, Perry et al. (2003) Journal of Neuroscience Research 72: 603-612).

[496] It is also contemplated that peptidomimetics or compounds (e.g., GLP1 peptidomimetics) disclosed herein Petition 870260086043, dated 08 / 24 / 2026, page 128 / 389 123 / 328 can be used to improve learning and memory, for example, by increasing neuronal plasticity and facilitating cell differentiation (see, During et al. (2003) Nature). Medicine 9:1173-1179). Furthermore, the compounds (e.g., an antibody-drug conjugate, a ligand-payload, and / or a payload) disclosed herein may also be used to preserve dopaminergic neurons and motor function in Parkinson's disease (see, for example, Greig et al. (2005) Abstract). 897.6, Society for Neuroscience, Washington, DC).

[497] In some embodiments, the peptidomimetics or compounds (e.g., GLP1 peptidomimetics) disclosed herein may also be used to treat a metabolic disorder. The metabolic disorder may be, for example, obesity, dyslipidemia, metabolic syndrome X, and pathologies resulting from islet insufficiency.

[498] Additional diseases that may be treated by a compound (e.g., an antibody-drug conjugate, a ligand-payload and / or a payload) of the present disclosure include autoimmune diseases, in particular those associated with inflammation, including, but not limited to, autoimmune diabetes, adult-onset diabetes, morbid obesity, Metabolic Syndrome X and dyslipidemia. For example, the anti-GLP1R antibody-drug conjugate may be used as a growth factor to promote islet growth in people with autoimmune diabetes. The compounds (e.g., an antibody-drug conjugate, a ligand-payload and / or a payload) described herein may also be useful in the treatment of congestive heart failure.

[499] In one aspect, the present disclosure provides a method for selectively targeting an antigen (e.g., GLP1R) on the surface of a cell with a peptidomimetic or compound disclosed herein. In one embodiment, the method for selectively targeting an antigen (e.g., GLP1R) on the surface of Petition 870260086043, dated 08 / 24 / 2026, page 129 / 389 124 / 328 A cell with a compound comprises the binding of the compound to a target antibody. In one embodiment, the cell is a mammalian cell. In one embodiment, the cell is a human cell. In one embodiment, the cell is a pancreatic cell or a brain cell. EXAMPLES

[500] The following examples illustrate specific aspects of the present description. The examples should not be interpreted as limiting, as they only provide a specific understanding and practice of the modalities and their various aspects.

[501] The abbreviations used in the Examples and throughout the specification are as follows: Table 1 Abbreviation Term AA1 amino acid 1 Ac acetyl ACN Acetonitrile or CH3CN Ac2O acetic anhydride AcOH acetic acid ADC antibody-drug conjugation aq. Aqueous Ar argon BnBr benzyl bromide BnOH benzyl alcohol Boc t-butoxycarbonyl Boc2O di-tert-butyl dicarbonate calcd. Calculated CbzCl benzyl chloroformate CD cyclodextrin CDI diimidazole carbonyl CHCl3 trichloromethane CH3CN acetonitrile CH3I methyl iodide Petition 870260086043, dated 08 / 24 / 2026, p. 130 / 389 125 / 328 DBU 1,8-diazabicyclo[5.4.0]undec-7-ene DCC dicyclohexylcarbodiimide DCM dichloromethane diastereomeric excess DIC N,N'-Diisopropylcarbodiimide DIPEA diisopropylethylamine DMAP 4-Dimethylaminopyridine DMF N,N-Dimethylformamide DMF-DMA N,N-dimethylformamide dimethyl acetate DMP Dess-Martin periodinane DMSO dimethyl sulfoxide dr diastereomeric ratio EDCI 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride enantiomeric excess eq. equivalent Et ethyl EtOAc Ethyl acetate EtOH ethanol Et3N Triethylamine Fmoc 9-fluorenylmethoxycarbonyl FmocCl 9-fluoromethyl chloroformate FmocOSu N-(9-Fluorenylmethoxycarbonyloxy)succinimide H2 hydrogen Hv irradiation with light HATU O-(7-azabenzotriazol-1-yl)N,N,N',N'-tetramethyluronium hexafluorophosphate HCl hydrochloride HOAt 1-hydroxy-7-azabenzotriazole Petition 870260086043, dated 08 / 24 / 2026, page 131 / 389 126 / 328 HOBt (HOBT) 1-hydroxybenzotriazole HOSu N-hydroxysuccinimide HPLC High-performance liquid chromatography h hour HRMS High-resolution mass spectrometry I2 iodine IPA isopropyl alcohol K2CO3 potassium carbonate KHSO4 potassium bisulfate KI potassium iodide KOAc potassium acetate KOH potassium hydroxide LCMS Liquid chromatography-mass spectrometry LiHMDS lithium hexamethyldisylazide LiI lithium iodide LiOH^H2O lithium hydroxide monohydrate Me methyl MPM (PMB) p-methoxybenzyl Ms mesyl (methanesulfonyl) MS mass spectrometry 4A MS Molecular sieves 4A MTBE methyl tert-butyl ether MW Molecular weight MeOH methanol MP Melting point N2 nitrogen NaClO sodium hypochlorite NaH sodium hydride NaOH sodium hydroxide Petition 870260086043, dated 08 / 24 / 2026, page 132 / 389 127 / 328 NaHCO3 sodium bicarbonate NaN3 sodium azide Na2SO4 sodium sulfate NBS N-bromosuccinimide NCS N-chlorosuccinimide NH4Cl ammonium chloride NH4HCO3 ammonium bicarbonate NIS N-iodosuccinimide NMO N-methylmorpholine oxide NMP N-methyl-2-pyrrolidinone NMR nuclear magnetic resonance PBr3 phosphorus tribromide Pd / C palladium on activated carbon Pd(OH)2 / C palladium hydroxide on activated carbon Pd(PPh3)4 tetrakis(triphenylphosphine)palladium PE petroleum ether PEG polyethylene glycol Ph phenyl Ph3PCH3Br methyltriphenylphosphonium bromide PMB-Cl 4-methoxybenzyl chloride Pr propyl Prep-HPLC high-pressure preparative liquid chromatography Prep-TLC thin-layer preparative chromatography prep-SFC preparative supercritical fluid chromatography psi pounds per square inch PTSA (or TsOH) p-toluenesulfonic acid Py (pyr) pyridine Petition 870260086043, dated 08 / 24 / 2026, page 133 / 389 128 / 328 PyBOP Benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate PE Petroleum ether MBHA resin MBHA resin (0.3~0.8 mmol / g, 100~200 mesh, 1% DVB) rt room temperature RT Retention time Rf retention factor in chromatography SC CO2 supercritical carbon dioxide SiO2 silicon dioxide SPPS solid-phase peptide synthesis t-Bu (tBu) tert-butyl t-BuOMe (MTBE, TBME) Methyl tert-butyl ether TBAF tetra-n-butylammonium fluoride TBAI tetra-n-butylammonium iodide TBDMS (TBS) t-butyldimethylsilyl TBDPS (BPS) t-butyldiphenylsilyl TEA triethylamine TES triethylsilyl TFA trifluoroacetic acid Tfa trifluoroacetamide Tf2O trifluoromethanesulfonic anhydride THF tetrahydrofuran TIPS (TIS) triisopropylsilane TLC thin layer chromatography TMEDA N,N,N',N'-tetramethylethylenediamine TMS trimethylsilyl TMSA trimethylsilyl azide TMSN3 trimethylsilyl azide Tol p-tolyl TPP triphenylphosphine Petition 870260086043, dated 08 / 24 / 2026, page 134 / 389 129 / 328 Tr (Trt) trityl (triphenylmethyl) TrtCl triphenylmethyl chloride Ts (Tos) p-toluenesulfonyl UV ultraviolet ZnBr2 Zinc bromide Example 1. General Methods

[502] All anhydrous reactions were carried out in dry glassware in an oven under an argon atmosphere with a stirrer or magnetic stirring, unless otherwise indicated. Rink Amide Linker was obtained from GL Biochem. All other anhydrous reagents and solvents were purchased from commercial sources and used without any further purification, unless otherwise indicated. Reactions (when possible) were monitored by thin-layer chromatography (TLC) on silica gel 60 F254 pre-coated plates and visualized by shortwave ultraviolet irradiation (254 nm; when applicable), stained with PMA (5% w / v) in EtOH or ninhydrin (5% w / v) in EtOH, followed by carbonization at ~200 °C. Unless otherwise specified, column chromatography (silica gel 60, 40 mm) was performed in air and under pressure (0.1-0.3 bar (10-30 kPa)). Bulk solvents (EtOAc, hexane, THF, DCM) for flash chromatography were distilled before use.IR spectra were recorded using an FT-IR spectrometer (Thermo NICOLET iS10) with a diamond head sample and are reported in wavenumbers (cm-1). Residual solvent content was recorded using GC (SHIMADZU-GC2030 and HS-20). Water content was recorded using a reaction instrument. Karl Fischer Mettler Toledo C30s. Melting points (MP) were measured via DSC (Differential Scanning Calorimeter, DSC 214). The report of inorganic salts was provided by a Thermo ICS-6000 ion chromatography detector. The purities of the synthetic intermediates after chromatographic purification were judged to be >90% by analysis of the 1H NMR spectra. Petition 870260086043, dated 08 / 24 / 2026, page 135 / 389 130 / 328 The purities of the final compounds were >95% (NMR analysis), after trituration with MeOH and MeCN (Honeywell, HPLC grade). General methods and instruments of NMR

[503] 1H NMR and 13C: 1H NMR spectra were recorded on a Bruker Avance 400 spectrometer (400 MHz, 1H, 100 MHz, 13C). Chemical shift (δ) values ​​are reported in ppm relative to residual chloroform (δ 7.26 ppm for 1H; δ 78.0 ppm for 13C). Multiplicities are indicated by s (singlet), d (doublet), t (triplet), q (quartet), p (pentet), h (heptet), dd (doublet of doublets), dt (doublet of triplets), dq (doublet of quartets), m (multiplet), and br (broad). The identification of the 1H and 13C signals was obtained using a combination of 1H, 13C, DEPT, COSY, HMBC, HMQC, and NOESY experiments. The coupling constants (J) are reported in Hertz (Hz). Example 2. General LC-MS methods and instruments Method 1

[504] This method was used for analysis of Tag5 Intermediates 1, 2, 3, 4, 5, 6, and 7. Instrument: Agilent 1200+6110MS (Table 2). A 2.5µm 4.6x50mm Xbridge Protein BEH C4 300A column was used for chromatography. Diode array (DAD) and evaporative light scattering (ELSD) were used as detection methods. The MS mode was positive electrospray ionization. The MS range was 50-1500. Mobile phase A was 0.04% TFA in water, and mobile phase B was 0.02% TFA in HPLC-grade ACN. The gradient was 50-100% B in 6 min. 50% B in 0.00 min, 50-100% B in 0.004.00 min with maintenance at 100% B for 1.5 min, 100-50% B in 5.516.00 min with maintenance at 50% B for 0.49 min. The flow rate was 1.50 mL / min. Table 2. Conditions for LC-MS Method 1 Parameter Value Instrument: Agilent 1200&6110&SEDEX85 Column: Xbridge Protein BEH C4 300a 2.5um 4.6x50mm Petition 870260086043, dated 08 / 24 / 2026, page 136 / 389 131 / 328 Column temperature: 40°C Mobile phase A (MPA) H2O + 0.04% (v / v) TFA Mobile phase B (MPB) ACN + 0.02% (v / v) TFA Flow rate: 1.5 mL / min (0.00-6.00) Gradient ratio: Time (min) 0 4 5.5 5.51 6 MPA (%) 50 0 0 50 50 MPB (%) 50 100 100 50 50 Detection: ELSD MS mode: Positive MS range: 50-1500 Da Method 2

[505] This method was used for analysis of Intermediate 8 of Tag5. Instrument: Waters H Class and SQD2 (Table 3). The gradient was 50-100% B in 3.40 min and maintained at 100% B in 3.40-3.85 min, 100-5% B in 0.01 min and then maintained at 5% for 0.64 min. The flow rate was 0.80 ml / min. Mobile phase A was H2O + mM NH4HCO3 and mobile phase B was HPLC grade THF. The column used for chromatography was a 2.1*50 mm Xbridge Shield RPC18 column (5 µm particles). Diode array detection (DAD) and positive electrospray ionization were used as detection methods. The MS range was 100-3000 Da. Table 3. Conditions for LC-MS Method 2 Parameter Value Instrument: Waters Class H and SQD2 Column: Xbridge Shield RP18 2.1*50mm, 5um Column temperature: 40°C Mobile phase A (MPA) H2O + 10 mM NH4HCO3 Petition 870260086043, dated 08 / 24 / 2026, page 137 / 389 132 / 328 Mobile Phase B (MPB) THF Flow Rate: 0.8 mL / min Gradient Ratio: Time (min) 0.00 0.40 3.40 MPA (%) 50 50 0 MPB (%) 50 50 100 Detection: 383 nm MS Mode: Positive MS Range: 100-3000 Da Method 3

[506] This method was used for the analysis of Intermediate 9 and Tag5. Instrument: Waters H Class and SQD2 (Table 4). The gradient was 70-100% B in 16.00 min and maintained at 100% B in 4.00 min, 100-70% B in 0.01 min and then maintained at 70% for 3 min, the flow rate was 1.0 ml / min. Mobile phase A was 10 mM ammonium bicarbonate and mobile phase B was HPLC grade THF. The column used for chromatography was an Xbridge C18 4.6 * 150 mm column (3.5 µm particles). Diode array (DAD) and positive electrospray ionization were used as detection methods. The MS range was 100-3000 Da. Table 4. Conditions for LC-MS Method 3 Parameter Value Instrument: Waters Class H and SQD2 Column: Xbridge C18 4.6*150mm, 3.5um Column temperature: 40°C Mobile phase A (MPA) H2O+10 mM NH4HCO3 Mobile phase B (MPB) THF Flow rate: 1.0 mL / min Gradient ratio: Time (min) 0.00 16.00 20.00 20.01 23.00 MPA (%) 30 0 0 30 30 MPB (%) 70 100 100 70 70 Petition 870260086043, dated 08 / 24 / 2026, pp. 138 / 389 133 / 328 Detection: 220 nm MS Mode: Positive MS Range: 100-3000 Method 4

[507] This method was used for analysis of Tagl-TCPs (Tag51AA). LC-MS conditions: Mobile phase: 1.5 mL / 4 LTF in water (solvent A) and 0.75 mL / 4 LTF in ACN (solvent B), using the elution gradient of 50%-100% (solvent B) over 1.35 minutes and holding at 100% for 0.9 minutes at a flow rate of 0.8 mL / min; Column: Xtimate C18 2.1*30 mm, 3 µm. Method 5

[508] This method was used for analysis of Tag1-2AA, Tag13AA, Tag1-4AA, Tag1-5AA, Tag1-6AA, Tag1-7AA, Tag1-10AA. LC-MS conditions: Mobile phase: 1.5 mL / 4 L TFA in water (solvent A) and 0.75 mL / 4 L TFA in ACN (solvent B), using a gradient from 10% to 80% (solvent B) over 6 minutes and maintaining at 80% for 0.5 minutes at a flow rate of 0.8 mL / min. Column: Xtimate C18 2.1*30 mm, 3 μm. Method 6

[509] This method was used for M2 analysis. LC-MS conditions: Reversed-phase LCMS was performed using a column Chromolith Flash RP-C18 25-3 mm, with a flow rate of 1.5 mL / min, eluting with a gradient of 10% to 80% ACN containing 0.02% TFA (solvent B) and water containing 0.04% TFA (solvent A). Method 7

[510] This method was used for analysis of Tag5-2AA, Tag53AA, Tag5-4AA, Tag5-5AA, Tag5-6AA, Tag5-7AA, Tag5-8AA, Tag5-9AA and Tag5-10AA. LCMS (BF) condition: Mobile phase: 1.5 mL / 4 L TFA in water (solvent A) and 0.75 mL / 4 L TFA in ACN (solvent B), using the elution gradient from 10%-80% (solvent B) over 6 minutes and holding at 80% for 0.5 minutes at a flow rate of 0.8 mL / min; Column: Xtimate C18 2.1*30 mm 3 µm; Wavelength: UV 220 nm, 254 nm; Column temperature: 50°C; ionization Petition 870260086043, dated 08 / 24 / 2026, pp. 139 / 389 134 / 328 MS: ESI. Method 8

[511] This method was used for analysis of Tag5-2AA, Tag53AA, Tag5-4AA, Tag5-5AA, Tag5-6AA, Tag5-7AA, Tag5-8AA, Tag5-9AA and Tag5-10AA. LCMS (CR) condition: Mobile phase: 1.5 mL / 4 L TFA in water (solvent A) and 0.75 mL / 4 L TFA in ACN (solvent B), using the elution gradient of 10%-80% (solvent B) over 6 minutes and holding at 80% for 0.5 minutes at a flow rate of 0.8 mL / min; Column: NanoChrom ChromCore 120 C18 3µm, 3.0*30 mm; Wavelength: UV 220 nm, 254 nm; Column temperature: 50°C; MS ionization: ESI. Method 9

[512] This method was used for analysis of Tag5-2AA, Tag53AA, Tag5-4AA, Tag5-5AA, Tag5-6AA, Tag5-7AA, Tag5-8AA, Tag5-9AA and Tag5-10AA. LCMS (BV) condition: Mobile phase: 1.5 mL / 4 L TFA in water (solvent A) and 0.75 mL / 4 L TFA in ACN (solvent B), using the elution gradient of 10%-80% (solvent B) over 6 minutes and holding at 80% for 0.5 minutes at a flow rate of 0.8 mL / min; Column: NanoChrom ChromCore 120 C18 3µm, 3.0*30 mm; Wavelength: UV 220 nm; Column temperature: 50°C; Ionization MS: ESI. Method 10

[513] This method was used for analysis of Tag5-2AA, Tag53AA, Tag5-4AA, Tag5-5AA, Tag5-6AA, Tag5-7AA, Tag5-8AA, Tag5-9AA and Tag5-10AA. LCMS (BK) condition: Instrument and column: Xtimate 3um, C18, 2.1*30mm S / N3U411701820 Mobile phase: 1.5mL / 4L TFA in water (solvent A) and 0.75mL / 4L TFA in ACN (solvent B), using a gradient of 10%-80% (solvent B) over 6 minutes and holding at 80% for 0.5 minutes at a flow rate of 0.8ml / min. ESI source, positive ion mode; Wavelength 220nm and 254nm, Oven temperature 50°C. Method 11

[514] This method was used for analysis of Tag4-10AA. Method Petition 870260086043, dated 08 / 24 / 2026, page 140 / 389 135 / 328 HPLC A: Column: YMC-Pack ODS-A 150*4.6mm, 5um; 2.75ML / 4L TFA in water (solvent A) and 2.5ML / 4LTFA in ACN (solvent B), using an elution gradient of 10%-80% (solvent B) over 10 minutes and maintaining at 80% for 5 minutes at a flow rate of 1.5 ml / min. Method 12

[515] This method was used for analysis of Tag4-10AA. LCMS condition: Reversed-phase LCMS was performed using a 25-3 mm Chromolith Flash RP-C18 column, with a flow rate of 1.5 mL / min, eluting with a gradient of 10% to 80% ACN containing 0.02% TFA (solvent B) and water containing 0.04% TFA (solvent A). Method 13

[516] This method was used for analysis of the intermediate AA10-AA9-AA8-OH. LC-MS conditions: Mobile phase: 1.5 mL / 4LTFA in water (solvent A) and 0.75 mL / 4LTFA in ACN (solvent B), using the 5%-95% elution gradient (solvent B) for 0.7 minutes and holding at 95% for 0.4 minutes at a flow rate of 1.5 mL / min; Column: Agilent Pursult 5 C18 20*2.0 mm. Method 14

[517] This method was used for analysis of DMB-AA9. Reversed-phase HPLC was performed using an Ultimate XB-C18 column, 3 gm, 3.0 x 50 mm. Mobile phase: 1.0% ACN in water (0.1% TFA) to 5% ACN in water (0.1% TFA) in 1 min; then, from 5% ACN in water (0.1% TFA) to 100% ACN (0.1% TFA) in 5 minutes; maintain at 100% ACN (0.1% TFA) for 2 minutes; return to 1.0% ACN in water (0.1% TFA) in 8.01 min and maintain for two minutes. Flow rate: 1.2 ml / min. Method 15

[518] This method was used for M2 analysis. HPLC conditions: Mobile phase: 1.0% ACN in water (0.1% TFA) to 5% ACN in water (0.1% TFA) in 1 minute; then from 5% ACN in water (0.1% TFA) to 100% ACN (0.1% TFA) in 5 minutes; hold at 100% ACN (0.1% TFA) for 2 minutes; return to 1.0% ACN in water (0.1% TFA) in Petition 870260086043, dated 08 / 24 / 2026, page 141 / 389 136 / 328 8.01 minutes and hold for two minutes. Flow rate: 1.2 ml / min. Speaker: Ultimate XB-C18, 3um, 3.0 * 50mm. ELSD LCMS

[519] Mobile Phase: 10 mM NH4OAC in water (solvent A) and ACN (solvent B), using an elution gradient from 10% to 80% (solvent B) over 5 minutes, holding at 80% for 1.95 minutes; 80% B changed to 10% B over 7 minutes, holding at 10% for 4 minutes at a flow rate of 0.8 mL / min. Column: Shimpack Scepter C18-120 1.9 μm, 2.1 x 100 mm. Example 3. DMB-AA9 Synthesis

[520] Scheme 1, below, describes the synthesis of DMB-AA9: Scheme 1

[521] Conditions: 1) (2,4-dimethoxyphenyl)methanamine (1.2 eq.), HATU (1.0 eq.), DIPEA (3 eq.), DMF (100 mL), 20°C, 2h, yield of 84%; 2) (a) PCl5 (1.5 eq.), TMSN3 (4 eq.), pyridine (8 V), 0 °C, 4h; (b) MeOH (4 eq.), 0 °C, 2 h, yield of 81%; 3) (a) NaOH (3 eq.), THF / H2O (2:1, 10 mL), 20 °C, 2h; (b) FmocOSu (1 eq.), aq. NaHCO3, 20°C, 2h; yield of 40.5%. Step 1: Synthesis of Methyl (2S)-4-[(2,4-Dimethoxyphenyl)methylamino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxo-butanoate (DMB-AA9-2)

[522] HATU was added to a solution of (3S)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methoxy-4-oxo-butanoic acid (DMB-AA9-1, 90 g, 243.66 mmol, 1 eq.) in DMF (200 mL). Petition 870260086043, dated 08 / 24 / 2026, p. 142 / 389 137 / 328 (101.91 g, 268.03 mmol, 1.1 eq.) and DIPEA (62.98 g, 487.32 mmol, 84.88 mL, 2 eq.) were mixed and stirred at 20°C for 30 min. Then, (2,4-dimethoxyphenyl)methanamine (44.82 g, 268.03 mmol, 40.37 mL, 1.1 eq.) was added and the mixture was stirred at 20°C for 1 h. Most of the reagent was consumed in TLC (PE / EtOAc = 2 / 1) and the desired compound was detected by LCMS. The reaction mixture was poured into DCM (1500 mL), washed with H2O (900 mL) and saturated citric acid (100 mL). The separated organic layer was washed with brine (1000 mL), dried over Na2SO4, and filtered. It was then concentrated under reduced pressure to yield the crude product as a light yellow solid. The crude product was triturated with EtOAc (600 mL) for 12 hours and filtered to yield the target compound. The desired compound DMB-AA9-2 (109 g, 197.59 mmol, yield 81.09%, purity 94%) was obtained as a white solid.ESI-MS (Método 10): RT = 3,896 min, mass calculation at C29H30O7N2H 519.2, m / z encontrado 519.1 [M+H]+. RMN (400 MHz, clorofórmio-d) δ = 7.76 (d, J = 7.5 Hz, 2H),7.61 (br dd, J = 3.6, 6.9 Hz, 2H), 7.44 - 7.37 (m, 2H), 7.36 -7.28 (m, 2H), 7.15 (d, J = 8,3 Hz, 1H), 6, 48 - 6, 38 (m, 2H), 6,15 (br s, 2H), 4,60 (br s, 1H), 4,44 - 4,26 (m, 4H), 4,26 - 4,19(m, 1H), 3, 84 - 3,72 (m, 9H), 2,97 (br dd, J = 4,4, 15,7 Hz, 1H), 2.73 (br dd, J =3.9, 15.7 Hz, 1H). Etapa 2: Síntese of (2S)-3-[1-[(2,4Dimetoxifenil)metil]tetrazol-5-il]-2-(9H-fluoren-9ilmetoxycarbonilamino)propanoato de metila (DMB-AA9-3) DMB-AA9-2 (a) PCI5 (1,5 eq.), TMSN3 (4 eq.), Py (8V), 0°C, 4h; (b) MeOH (4 eq.), 0°C, 2h, 81% of heat DMB-AA9-3 2)

[523] To a suspension of the compound DMB-AA9-2 (100 g, 192.84 mmol, 1 eq.) in pyridine (800 mL), TMSN3 (88.87 g, 771.37 mmol, 101.45 mL, 4 eq.) was added, followed by the addition of PCl5 (60.24 g, 289.26 mmol, 1.5 eq.) in portions. The temperature was Petition 870260086043, dated 08 / 24 / 2026, p. 143 / 389 138 / 328 maintained below 0 °C using an ice-brine bath. The reaction mixture was stirred at 0 °C for 5 h. LCMS showed that most of the reagent was consumed. Then, MeOH (24.71 g, 771.37 mmol, 31.21 mL, 4 eq.) was added dropwise and the reaction mixture was stirred at 0 °C for 1 h. TLC (PE / EtOAc = 2 / 1) and LCMS showed that most of the reagent was consumed, and the desired compound was detected as a main peak. The reaction was stopped with MeOH (20 mL) and saturated aqueous NaHCO3 (1000 mL x 2), and extracted with EtOAc (1000 mL x 3). The aqueous layers were treated with 8-10% NaClO (1000 mL). The combined organic layers were concentrated under reduced pressure to generate a residue, which was redissolved in EtOAc (2000 mL) and washed with saturated citric acid (500 mL x 2) and brine (1000 mL), dried over Na2SO4, and concentrated under reduced pressure to generate a residue. The crude product was used directly in the next step without any further purification.The desired compound DMB-AA93 (97 g, 156.86 mmol, 81.34% yield, 87.9% purity) was obtained as a yellow oil. LC-MS: RT = 4.310 min, calculated mass for C29H29N5O6 H 544.2 [M+H]+, m / z found 544.2. [M+H]+, Method 10. 1H NMR (400 MHz, chloroform-d) δ = 7.68(d, J = 7.6 Hz, 2H), 7.48 (br d, J = 7.4 Hz, 2H), 7.37 - 7.25(m, 3H) - 4.22 (m, 2H), 4.20 - 4.10 (m, 1H), 3.71 - 3.63 (m, 9H),3.54 - 3.41 (m, 1H), 3.26 (dd, J = 4.6, 16.3 Hz, 1H) ppm. Step 3: Synthesis of (2S)-3-[1-[(2,4dimethoxyphenyl)methyl]tetrazol-5-yl]-2-(9H-fluoren-9ylmethoxycarbonylamino)propanoic acid (DMB-AA9) DMB-AA9-3 (a) NaOH (3 eq.), THF / H2O (2:1, 10 mL), 20°C, 2h; (b) FmocOSu (1 eq.), aq. NaHCO3, 20°C, 2h; 40.5% yield 3) DMB-AA9

[524] To a solution of the compound DMB-AA9-3 (95 g, 174.77 mmol Petition 870260086043, dated 08 / 24 / 2026, page 144 / 389 139 / 328 eq) in THF (600 mL) and H2O (100 mL), NaOH (20.97 g, 524.31 mmol, 3 eq) was added and the reaction mixture was stirred at 20 °C for 2 h. LCMS showed that the reagent was consumed. The pH of the reaction mixture was adjusted to 7-8 with citric acid and the mixture was diluted with H2O (200 mL) and then extracted with TBME (300 mL x 2). To the aqueous layer, NaHCO3 (44.05 g, 524.31 mmol, 20.39 mL, 3 eq) and FmocOSu (58.96 g, 174.77 mmol, 1 eq) in THF (600 mL) were added, then the reaction mixture was stirred at 10 °C for 12 h. LCMS showed that the desired compound was detected as a main peak. The reaction was concentrated under reduced pressure to remove THF, then poured into saturated NaHCO3 (500 mL) and H2O (300 mL), and extracted with TBME (500 mL x 3). The aqueous layer was extracted with EtOAc / MeOH (10 / 1, 800 mL x 3) The combined EtOAc layers were washed with saturated NaHCO3 (200 mL) and brine (200 mL), then dried over Na2SO4 and concentrated under reduced pressure to generate a residue. The crude product was ground with TBME:ACN:EtOAc (10:1:1, 250 mL) for 12 h at 20 °C and filtered to generate a light yellow solid. The compound DMB-AA9 (38 g, 70.90 mmol, yield 40.57%, purity 98.8%) was obtained as a light yellow solid. LCMS: RT = 3.207 min, calculated mass for C28H27N5O6 H 530.2 [M+H]+, m / z found 530.2 [M+H]+, Method 7. HPLC purity: 98.84% after trituration (Method 14 was used for the analysis of DMB-AA9). 1H NMR (400MHz, Methanol-dd δ = 7.77 (d, J = 7.5 Hz, 2H), 7.62 (br d, J =7.3 Hz, 2H), 7.40 - 7.16 (m, 5H), 6.56 - 6.43(m, 2H) - 3.35 (m, 1H) ppm. SFC ee = 98.53-1.47 = 97.06%. Example 4. Synthesis (LPPS) of M2 in Tag1 4.1 Summary of Tag 1

[525] The synthetic route to make Tag1 is shown in Scheme 2. Scheme 2 Petition 870260086043, dated 08 / 24 / 2026, p. 145 / 389 140 / 328 Tag1-1 Tag1-2 OH Tag 1-3 Tag1-4 Tag1

[526] Reagents and conditions: a) 1-bromodocosane (2.2 eq.), K2CO3 (6 eq.), DMF / THF, 90°C, 12 h, 99%; b) NaBH4 (5 eq.), EtOH (1 V), THE (10 V), 70°C, 12 h, 96%; c) FmocNH2 (2 eq.), MeSO5H (0.3 eq.), toluene / THF, 110°C, 36 h, 82%; d) 20% piperidine / THF (10 V), 20°C, 2 h, 92%. Total yield: 71.6% in 4 steps. Total yield: 71.6% for 4 steps.

[527] The synthesis was reported in U.S. Patent Application Publication No. 2012 / 0296074 by Hirai et al. Alkylation of Tagl-1 with 1-bromodocosane produced Tagl-2, which was reduced by sodium borohydride to form the alcohol Tagl-3. The compound Tagl-4 was obtained from Tagl-3 via nucleophilic substitution of 9-fluorenylmethylcarbamate, using methanesulfonic acid as a catalyst. The reaction yield was slightly improved by using a cosolvent (toluene / THF) instead of toluene (82% vs 60%). Deprotection of Fmoc in Tagl-4 was performed using piperidine / THF and produced Tagl with a total yield of 72%. U.S. Patent Application Publication No. 2012 / 0296074 by Hirai et al. It reported a 45% yield for the deprotection of Tagl-4 Fmoc using DBU / DCM. Step a: Synthesis of Bis(4-docosoxyphenyl)methanone (Tagl-2) O o .................:... K2CO3 (6 eq.), DMF / THF, UU Tag1-1 90 °C, 12 h, 99%; Tag1-2

[528] To a mixture of compound Tagl-1 (10 g, 46.68 mmol, 1.0 eq.) and 1-bromodocosane (40.00 g, 102.70 mmol, 2.2 eq.) in DMF Petition 870260086043, dated 08 / 24 / 2026, p. 146 / 389 141 / 328 (200 mL) and THF (40 mL), K2CO3 (38.71 g, 280.09 mmol, 6 eq.) was added and the mixture was stirred at 90 °C for 12 h. The reagent was consumed and a new spot with lower polarity was formed on the TLC (PE / EtOAc = 2 / 1). The reaction mixture was poured into water (1000 mL) and stirred for 1 h. Then, the precipitated solid was collected by filtration and washed with water (200 mL χ2). The obtained solid was triturated with acetone (500 mL) and collected by filtration from the acetone-washed suspension. After filtration, the obtained solid was dried under reduced pressure to yield Tag1-2 (38.8 g, 46.67 mmol, 99.97% yield) as a white solid.

[529] Composite Tag1-2 (C57H98O3, MW: 830.75): 1H NMR (400 MHz, CDCl3) δ = 7.78 (d, J = 8.8 Hz, 4H), 6.95 (d, J = 8.8 Hz, 4H), 4.04 (t, J = 8.8 Hz, 4H), 4H), 1.86 - 1.78 (m, 4H), 1.51 - 1.43 (m, 4H), 1.26 (s, 72H), 0.89 (t, J = 6.8 Hz, 6H) ppm. Step b: Synthesis of Bis(4-docosoxyphenyl)methanol (Tag1-3) 96%; Tag1-2 Tag 1-3

[530] A solution of the Tag1-2 compound (35 g, 42.10 mmol, 1 eq.) in THF (500 mL) and EtOH (25 mL) was heated to 70 °C. Then, NaBH4 (7.96 g, 210.49 mmol, 5.0 eq.) was added slowly and the mixture was stirred at the same temperature for 20 h. TLC (PE / EtOAc = 3 / 1) showed that the reagent was completely consumed and a new spot was detected. The reaction mixture was cooled on ice and 1 N hydrochloric acid (80 mL) was added dropwise. The THF was evaporated, water (450 mL) was added, and 1 N hydrochloric acid was added until pH 5-7. The suspension was filtered and the resulting crystals were washed with water and methanol to obtain the product. Tag1- 3 (34 g, 40.80 mmol, 96.91% yield) as a white solid.

[531] Compound Tag1-3 (C57H100O3, MW: 832.77):1H NMR (400 MHz, chloroform-d) δ = 7.29 - 7.25 (m, 4H), 6.88 - 6.84 (m, 4H), 5.77 (d, J = 2.8 Hz, 1H), 3.94 (t, J = 6.7 Hz, 4H), 2.09 (d, J Petition 870260086043, dated 8 / 24 / 2026, p. 147 / 389 142 / 328 = 3.3 Hz, 1H), 1.81 − 1.73 (m, 4H), 1.48 − 1.41 (m, 4H), 1.35 1.26 (m, 72H), 0.91 − 0.87 (m, 6H) ppm Stage c: Synthesis of 9H-Fluoren-9-ylmethyl N-[bis(4docoxyphenyl)methyl]carbamate (Tag1-4) OH NHFmoc C22H45^OJ^J XjA.0-C22H45 FmocNH2(2 eq.), MeSO3H (0.3 eq.), Χ / Χ.Ο^Ο22Η45toluene / THF, 110 °C, 36h, 82% Table1-3 Table1-4

[532] To a mixture of Tag1-3 (10 g, 12.00 mmol, 1 eq.) and 9H-fluoren-9-ylmethyl carbamate (FmocNH2, 5.74 g, 24.00 mmol, 2.0 eq.) in toluene (200 mL), MsOH (345.97 mg, 3.60 mmol, 256.27 pL, 0.3 eq.) was added and the mixture was stirred at 110 °C for 36 h. Most of the reagent was consumed and new spots were formed on TLC (PE / EtOAc = 10 / 1). The reaction mixture was poured into 5% NaHCO3 (30 mL) and stirred for 1 h. Then, the precipitated solid was collected by filtration and washed with water (50 mL). The solid obtained was ground with ACN (200 mL) and collected by filtration and washed with methanol. After filtration, the solid obtained was dried under reduced pressure to yield Tag1-4 (11 g, 9.91 mmol, yield of 82.58%, purity of 95%) as a whitish solid.

[533] Compound Tag1-4 (C72H111NO4, MW: 1053.85):1H NMR (400 MHz, Chloroform-d) δ = 9.89 (s, 1H), 7.78 (br d, J = 8.4 Hz, 2H), 7.61 (br d, J = 7.4 Hz, 2H), 7.44 - 7.31 (m, 4H), 7.147.10 (m, 1H), 7.12 (d, J = 8.6 Hz, 2H), 6.98 (dd, J = 8.7,19.2 Hz, 1H), 6.88 - 6.75 (m, 4H), 5.87 (br s, 1H), 4.43 (d, J =7.0 Hz, 1H), 4.28 - 4.21 (m, 1H), 4.04 (dt, J = 2.9, 6.5 Hz, 1H), 3.99 - 3.85 (m, 4H), 1.82 - 1.74 (m, 4H), 1.59 (br s, 4H),1.27 (s, 72H), 0.91 - 0.89 (m, 6H) ppm. Step d: Synthesis of Bis(4-docosoxyphenyl)methanamine (Tag1-5) NHFmoc NH2 / χΛχ / χ d / ^A> / (322^45--,-)---- / / / / / / --.-)--C22H45 20% piperidine / THF (10 V) C22H45 ^-, / ^,, / / / / --.-).-(322^45 20°C, 2h, 92% Tag1-4 Tag1

[534] For a solution of Tag1-4 (11 g, 10.43 mmol, 1 eq.) in Petition 870260086043, dated 08 / 24 / 2026, pp. 148 / 389 143 / 328 THF (80 mL) was added to piperidine (20 mL). The mixture was then stirred at 20 °C for 2 h. TLC (PE / EtOAc = 3 / 1) showed that the reagent was completely consumed and a new spot was detected. ACN (400 mL) was added to the reaction solution and the resulting suspension was filtered and washed with ACN (100 mL x 2) to yield a whitish solid. The crude product Tag1-5 (8 g, 9.61 mmol, 92.14% yield) was obtained as a white solid. It was dried under reduced pressure and used in the subsequent synthesis of Tag1-M2.

[535] Compound Tag1-5 (C57H101NO2, MW: 831.78): 1H NMR (400 MHz, Chloroform-d) δ = 7.29 (s, 4H), 6.86 (d, J = 8.6 Hz, 4H), 5.15 (s, 1H), 3.95 (t, J = 6.6 Hz, 4H), 1.80 - 1.76 (m, 4H), 1.49 - 1.43 (m, 4H), 1.29 (s, 72H), 0.91 (t, J = 6.8 Hz, 6H) ppm. 4.2 Tag1-M2 Synthesis

[536] Figure 2 and Table 5 describe the synthesis of M2 using Tag1. Table 5. Reação de acoplamento eq molar para Tag1 (0,04 mmoL) de-Fmoc Produto Etapa# aminoácido DIC HOAt Etapa# Cpd# MS (M+H)+ Rendimentoc 1 AA1 1,5 eq.b 1,5 eq. 1,5 eq. 2 0Vd Tag1-1AA 221,1 [M- Tag1+2H]+ 88,2% 2 AA2 1,5 eq. 1,5 eq. 1,5 eq. 2 0V Tag 1-2AA 585,4 [M- Tag1+2H]+ 84,3% 3 AA3 1,5 eq. 1,5 eq. 1,5 eq. 2 0V Tag1-3AA 778,5 [M- Tag1+2H+Na]+ 82,7% 4 AA4 1,5 eq. 1,5 eq. 1,5 eq. 2 0V Tag1-4AA 787,4 [M-Tag1- tBu-TBS+4H]+ 93,1% 5 AA5 1,5 eq. 1,5 eq. 1,5 eq. 2 0V Tag1-5AA 1002,7 [M- Tag1-tBu- TBS+4H]+ 97,2% 6 AA6 1,5 eq. 1,5 eq. 1,5 eq. 2 0V Tag1-6AA 1067,7 [M- Tag1-tBu- 2TBS+5H] 84,7% Petição 870260086043, de 24 / 08 / 2026, pág. 149 / 389 144 / 328 7 AA7 5 eq. 4,5 eq. 4,5 eq. 2 0V Tag1-7AA 1282,7 [M- Tag1-tBu- 2TBS+5H]+ 60,4% 8 AA10- AA9- AA8-OHa 1,05 eq. HATUe (1,2 eq.) / Tag1-10AA 786,7 [M-Tag1- tBu-3TBS-DMB- Trt+9H]2+ bruto 9 Clivagem M2 786,8 [M+H]+ 18,7% Tag1-8AA cannot be separated by precipitation in ACN, so Tag1-10AA was obtained from a coupling reaction of Tag1-7AA with AA10-AA9-AA8 using 1.2 eq of HATU (substituting HOAt), after cleavage of Tag1 to generate M2b. Eq.: molar equivalent of the reagent. Yield: crude oil yield. dV: volume (mL) for Tag (gram). In step 8, the coupling reagent (DIC) was replaced by HATU. General Procedure A for amide coupling reactions to generate N-Fmoc-Tag1-nAA

[537] A solution of Tag1 or Tag1-(n-1)AA (1 eq.) and AAn (1.5 eq.) in DCM (20 V), DIC (1.5 eq.) and HOAt (1.5 eq.) were added. The solution was stirred at 20 °C for 2 h. TLC (PE / EtOAc = 1 / 1) showed that the reagent was completely consumed, and a new spot was detected, which was subsequently confirmed by LC-MS after cleavage of a small amount. ACN (80 V) was added to the reaction solution and the resulting suspension was filtered and washed with MeOH (20 V x 2) to provide a whitish solid. The crude product was dried under reduced pressure and N-Fmoc-Tag1-(n)AA was obtained as a white solid and used directly in the next step. General procedure B for Fmoc deprotection to generate Tag1-nAA

[538] A solution of N-Fmoc-Tag1-(n)AA (1 eq.) in 20% piperidine in THF (20 V) was stirred at 20 °C for 1 h. TLC (PE / EtOAc = 1 / 1) showed that the reagent was completely Petition 870260086043, dated 08 / 24 / 2026, pp. 150 / 389 145 / 328 consumed and the desired point was detected. ACN (80 V) was added to the reaction solution and the resulting suspension was filtered and washed with ACN (20 V χ 2) to obtain a whitish solid. The crude product Tag1-nAA was dried under reduced pressure and used directly in the next step. Step 1: Synthesis of (2S)-2-Amino-N-[bis(4docosoxyphenyl)methyl]-5-(3,5-dimethylphenyl) pentanamide (Tag11AA) Tag1-1AA

[539] A solution of Tag1 (6 g, 7.21 mmol, 1 eq.) and AA1 (4.80 g, 10.81 mmol, 1.5 eq.) in DCM (100 mL), DIC (1.18 g, 9.37 mmol, 1.45 mL, 1.3 eq.) and HOAt (1.28 g, 9.37 mmol, 1.31 mL, 1.3 eq.). The solution was stirred at 20 °C for 2 h. TLC (PE / EtOAc = 1 / 1) showed that the reagent was completely consumed, and a new spot was detected, which was subsequently confirmed by the crude cleavage test. ACN (400 mL) was added to the reaction solution, and the resulting suspension was filtered and washed with MeOH (100 mL χ 2) to provide a whitish solid. The crude product was dried under reduced pressure, and N-Fmoc-Tag1-1AA (8 g, 6.36 mmol, yield of 88.23%) was obtained as a white solid and used directly in the next step. LCMS (ESI): RT = 4.266 min, calculated mass for C28H31N2O3+ 443.23, m / z found 443.20 [M-TAG-1+H]+; (Tag1 = C57H99O2, MS = 815.76).

[540] Piperidine (20 mL) was added to a solution of N-Fmoc-Tag1-1AA (8 g, 6.36 mmol, 1 eq.) in THF (80 mL). Then, Petition 870260086043, dated 08 / 24 / 2026, pp. 151 / 389 146 / 328 The mixture was stirred at 20 °C for 1 h. TLC (PE / EtOAc = 1 / 1) showed that the reagent was completely consumed and the desired endpoint was detected. ACN (400 mL) was added to the reaction solution and the resulting suspension was filtered and washed with ACN (100 mL χ²) to generate a whitish solid. The crude product Tag1-1AA, as a white solid, was dried under reduced pressure and used directly in the next step. Step 2: Synthesis of (2S)-2-[[(2S)-2-Amino-3-[4-[4-(4azidobutoxy)-2-ethyl-phenyl]phenyl]propanoyl]amino]-N-[bis(4docosoxyphenyl)methyl]-5-(3,5-dimethylphenyl)pentanamide (Tag1-2AA) General A for amide coupling using Tag1-1AA (7 g, 6.76 mmol). The crude product N-Fmoc Tag1-2AA (11 g, white solid) was dried and used directly in the next step. LCMS (ESI): RT = 5.759 min, mass calculated for C49H55NgO5+ 807.42, m / z found 807.40 [M-TAG-1+H]+; (Tag1 = C57H99O2, MS = 815.76).

[542] The deprotection reaction was carried out according to general procedure B for Fmoc deprotection. Tag1-2AA (8 g, 5.71 mmol, yield of 84.27%) was obtained as a white solid. LCMS (ESI): RT = 3.568 min, calculated mass for C34H45NgO3+ 585.35, m / z found 585.50 [M-TAG-1+H]+; (TAG-1 = C57H99O2, MS=815.76). Step 3: Synthesis of tert-Butyl(3S)-3-Amino-4-[[(1S)-1-[[4[4-(4-azidobutoxy)-2-ethyl-phenyl]phenyl]methyl]-2-[[(1S)-1[bis(4-docosoxyphenyl)methylcarbamoyl]-4-(3,5-dimethylphenyl) butyl]amino]-2-oxo-ethyl]amino]-4-oxo-butanoate (Tag1-3AA) Petition 870260086043, dated 08 / 24 / 2026, p. 152 / 389 147 / 328

[543] The reaction was carried out according to general procedure A for amide coupling using Tag1-2AA (7 g, 5.00 mmol). N-Fmoc-Tag1-3AA (8.9 g, 4.96 mmol, 99.25% yield) was obtained as a yellow solid. LCMS (ESI): RT = 5.388 min, calculated mass for C53H60N7O8+922.44, m / z found 922.50 [MTAG-1+H]+; (Tag1 = C57H99O2, MS = 815.76).

[544] The deprotection reaction was performed according to general procedure B for deprotection of Fmoc. Tag1-3AA (6.5 g, 4.14 mmol (yield of 83.36%) was obtained as a white solid. LCMS (ESI): RT = 4.294 min, calculated mass for C38H50N7O6+700.37, m / z found 700.50 [M-Tag-1+H]+; (TAG-1 = C57H99O2, MS = 815.76). Step 4: Synthesis of tert-Butyl (3S)-3-[[(2S)-2-Amino-3-tertbutoxy-propanoyl]amino]-4-[[(1S)-1-[[4-[4-(4-azidobutoxy)-2ethyl-phenyl]phenyl]methyl]-2-[[(1S)-1-[bis(4docosoxyphenyl) methylcarbamoyl]-4-(3,5-dimethylphenyl)butyl]amino]-2-oxoethyl]amino]-4-oxo-butanoate (Tag1-4AA)

[545] The reaction was carried out according to general procedure A for amide coupling using Tag1-3AA (6.5 g, 4.14 mmol, 1 eq.). N-Fmoc-Tag1-4AA (8 g, 4.13 mmol, yield of (99.86%) was obtained as a yellow solid. LCMS (ESI): RT = 5.198 min, calculated mass for C56H65N8O10+1009.47, m / z found Petition 870260086043, dated 08 / 24 / 2026, page 153 / 389 148 / 328 1009.60 [M-TAG-1+H]+; (Tag1 = C57H99O2, MS = 815.76).

[546] The deprotection reaction was carried out according to general procedure B for Fmoc deprotection. Tag1-4AA (6.6 g, 3.85 mmol, 93.19% yield) was obtained as a white solid. LCMS (ESI): RT = 3.540 min, calculated mass for C41H55N8O8+787.41, m / z found 787.50 [M-TAG-1+H]+; (Tag1 = C57H99O2, MS = 815.76). Step 5: Synthesis of tert-Butyl (3S)-3-[[[(2S)-2-[[(2S,3R)-2Amino-3-tert-butoxy-butanoyl]amino]-3-tert-butoxypropanoyl]amino]-4-[[(1S)-1-[[4-[4-(4-azidobutoxy)-2-ethylphenyl] phenyl]methyl]-2-[[(1S)-1-[bis(4 docosoxyphenyl)methylcarbamoyl]-4-(3,5-dimethylphenyl)butyl]amino]-2-oxo-ethyl]amino]-4-oxo-butanoate (Tag1-5AA)

[547] The reaction was carried out according to general procedure A for amide coupling using Tag1-4AA (6.60 g, 3.85 mmol, 1 eq.). N-Fmoc-Tag1-5AA (8.0 g, 3.82 mmol, yield of (99.25%) was obtained as a white solid. LCMS (ESI): RT = 5.024 min, mass calculated for C60H72N9O12+1110.52, m / z found 1110.60 [M-TAG-1+H]+; (Tag1= C57H99O2, MS = 815.76).

[548] The deprotection reaction was carried out according to general procedure B for Fmoc deprotection. Tag1-5AA (7.0 g, 3.74 mmol, 97.89% yield) was obtained as a white solid, which was used directly in the next step. LCMS (ESI): RT = 3.542 min, calculated mass for C45H62N9O10+888.45, m / z found 888.50 [M-TAG-1+H]+; (Tag1 = C57H99O2, MS = 815.76). Step 6: Synthesis of tert-Butyl (3S)-3-[[[(2S)-2-[[(2S,3R)-2[[2-Amino-3-(2-fluorophenyl)-2-methyl-propanoyl]amino]-3-tertbutoxy-butanoyl]amino]-3-tert-butoxy-propanoyl]amino]-4Petition 870260086043, of 08 / 24 / 2026, p. 154 / 389 149 / 328 [[(1S)-1-[[4-[4-(4-azidobutoxy)-2-ethyl-phenyl]phenyl]methyl]-2[[(1S)-1-[bis(4-docosoxyphenyl)methylcarbamoyl]-4-(3,5dimethylphenyl)butyl]amino]-2-oxo-ethyl]amino]-4-oxo-butanoate (Tag1-6AA)

[549] The reaction was carried out according to general procedure A for amide coupling using Tag1-5AA (7.00 g, 3.74 mmol, 1 eq.). N-Fmoc Tag1-6AA (7.3 g, 3.21 mmol, yield of (85.87%) was obtained as a white solid. LCMS (ESI): RT = 5.024 min, mass calculated for C70H82FNioO13+1289.60, m / z found 1289.60 [M-TAG-1+H]+; (Tag1 = C57H99O2, MS = 815.76).

[550] The deprotection reaction was carried out according to general procedure B for Fmoc deprotection. Tag1-6AA (6.5 g, 3.17 mmol, 98.69% yield) was obtained as a white solid. LCMS (ESI): RT = 3.699 min, mass calculated for C55H72FNioOii+1067.53, m / z found 1067.60 [M-TAG-1-3tBu +4H]+; (TAG-1 = C57H99O2, MS = 815.76). Step 7: Synthesis of tert-Butyl (3S)-3-[[(2S)-2-[[(2S,3R)-2[[2-[[(2S,3R)-2-Amino-3-tert-butoxy-butanoyl]amino]-3-(2fluorophenyl)-2-methyl-propanoyl]amino]-3-tert-butoxybutanoyl]amino]-3-tert-butoxy-propanoyl]amino]-4-[[(1S)-1-[[4[4-(4-azidobutoxy)-2-ethyl-phenyl]phenyl]methyl]-2-[[(1S)-1[bis(4-docosoxyphenyl)methylcarbamoyl]-4-(3,5dimethylphenyl)butyl]amino]-2-oxo-ethyl]amino]-4-oxo-butanoate (Tag1-7AA) Petition 870260086043, de 24 / 08 / 2026, p. 155 / 389 150 / 328 Member1-6AA Member 1-7 AA

[551] To a solution of Tag1-6AA (6.5 g, 3.17 mmol, 1 eq.) and AA7 (6.30 g, 15.85 mmol, 5.0 eq.) in DCM (100 mL) were added DIC (1.80 g, 14.26 mmol, 2.21 mL, 4.5 eq.) and HOAt (1.94 g, 14.26 mmol, 2.00 mL, 4.5 eq.). The solution was then stirred at 20 °C for 2 h. TLC (PE / EtOAc = 1 / 1) showed that the reagent was completely consumed, and a new spot was detected. ACN (400 mL) was added to the reaction solution, but only a small solid was formed. H2O (50 mL) was added, and the resulting suspension was filtered and then washed with ACN (200 mL x 2) to give a whitish solid. (Note: filtration was very slow due to the small solid particles.) N-FmocTag1-7AA (6.6 g, 2.72 mmol, yield of 85.69%) was obtained as a white solid that was used directly in the next step. LCMS (ESI): RT = 5.437 min, mass calculated for C74H89FN11O15+ 1390.46, m / z found 1390.70 [M-TAG-1+H]+; (Tag1 = C57H99O2, MS = 815.76).

[552] Piperidine (20 mL) was added to a solution of N-Fmoc-Tag1-7AA (7.80 g, 3.21 mmol, 1 eq.) in THF (80 mL). The solution was then stirred at 20 °C for 2 h. TLC (PE / EtOAc = 1 / 1) showed that the reagent was completely consumed and new spots were detected. The reaction mixture was added to ACN / H2O = 1 / 8 (600 mL) and the resulting suspension was filtered. (Note: filtration was very slow due to small solid particles.) The filter cake was ground with THF / ACN = 1 / 12 (500 mL) and filtered. Then, the filter cake was washed with ACN (50 mL x 3) to provide the crude product. Tag1 -7AA (5.0 g, 2.26 mmol, 70.54% yield) was obtained as a white solid that was used directly in the next step. LCMS Petition 870260086043, dated 08 / 24 / 2026, page 156 / 389 151 / 328 (ESI): RT= 3,550 min, mass calculated for C45H62N9O10+ 888.45, m / z found 888.50 [M- TAG-1+H]+; (Tag1 = C57H99O2, MS=815.76). Step 8: Synthesis of (3S)-4-[[(1S)-1-[[4-[4-(4-Azidobutoxy)2-ethyl-phenyl]phenyl]methyl]-2-[[(1S)-1-carbamoyl-4-(3,5dimethylphenyl)butyl]amino]-2- oxo-ethyl]amino]-3-[[(2S)-2[[(2S,3R)-2-[[3-(2-fluorophenyl)-2-[[(2S,3R)-3-hydroxy-2-[[2[[(2S)-2-[[3-[2-(1H-imidazol-5-yl) Acid ethylamino]-2,2dimethyl-3-oxo-propanoyl]amino]-3-(1H-tetrazol-5yl)propanoyl]amino]acetyl]amino]butanoyl]amino]-2-methylpropanoyl]amino]-3-hydroxy-butanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxo-butanoic acid (Tag1-M2) 8) amide formation 9) cleavage Tag1-7AA

[553] To a solution of Tag1-7AA (300 mg, 135.86 μmol, 1 eq.) and AA10-AA9-AA8-OH (116.11 mg, 142.66 μmol, 1.05 eq.) in DMF (0.5 mL) and DCM (1.5 mL), HATU (61.99 mg, 163.03 μmol, 1.2 eq.) was added. The mixture was then stirred at 20 °C for 2 h. A TLC (PE / EtOAc = 1 / 1) showed that the reagent was completely consumed and a new spot was detected. The reaction mixture was extracted with water (50 mL) and then extracted with DCM (80 mL x 2). The combined organic layers were washed with brine (30 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure to yield the compound Tag1-10AA (408 mg, crude). LCMS (ESI): RT = 3.94 min, m / z calculated for C75H101FN20O17, 786.375 [M-Tag1+H]+; m / z found 786.8; (Tag1 = C57H99O2, MS = 815.76). LC-MS conditions: Method 7.

[554] Crude Tag1-10AA was subjected to acid cleavage using TFA cocktail (10 mL, TFA:Tips:H2O = 95:2.5:2.5) for 1.5 h. The reaction mixture was filtered and the filtrate was concentrated to provide a residue, which was purified by prep-HPLC (TFA; mobile phase: [water (TFA)-ACN] B%: 28%-58%, 12 min condition). M2 (40 Petition 870260086043, dated 08 / 24 / 2026, pp. 157 / 389 152 / 328 mg, 25.45 pmol, yield of 18.73%) was obtained as a white solid. LC-MS: RT = 3.942 min, m / z calculated for C75H101FN20O17, 786.375 [M+H]+; m / z found 786.8. LC-MS conditions: Method 7.

[555] HPLC: RT = 9.66 min, purity of 92.86%. HPLC Method A: Column: YMC-Pack ODS-A 150 x 4.6 mm, 5 µm; 2.75 mL / 4 LTFA in water (solvent A) and 2.5 mL / 4 LTFA in ACN (solvent B), using an elution gradient from 10% to 80% (solvent B) for 10 minutes and maintaining at 80% for 5 minutes at a flow rate of 1.5 mL / min. Synthesis of 2-[[(2S)-3-[l-[(2,4Dimethoxyphenyl)methyl]tetrazol-5-yl]-2-[[2,2-dimethyl-3-oxo-3-[2(3-tritylimidazol-4yl)ethylamino]propanoyl]amino]propanoyl]amino]acetic acid (AA10-AA9-AA8-OH) o 22 AA10-AA9-AA8-OH

[556] To a solution of DMB-AA9 (3.23 g, 6.10 mmol, 2 eq) and Dl EA (1.58 g, 12.20 mmol, 2.12 mL, 4 eq) in DMF (20 mL), HATU (2.32 g, 6.10 mmol, 2 eq) was added in a portion at 20 °C. The mixture was stirred at 20 °C for 0.2 h. Compound 21 (2.82 g, 3.05 mmol, 37.94% purity, 1 eq) was added and the mixture was stirred at 20 °C for 2 h. After completion, the mixture was filtered and the collected resin was washed with DMF (25 mL χ 3), DCM (25 mL χ 3) to provide the crude product Fmoc-22 in chlorotrityl chloride (CTC) resin (4.38 g, 3.05 mmol, 99.93% yield, 60% purity) as a light yellow solid. LCMS (ESI): RT = 0.942 min, m / z calculated for CaOHaONeO?^, 609, 22, [M+Na]+; m / z found 609, 1; LC-MS conditions: Method 13.

[557] Piperidine (8 mL) was added to a solution of Fmoc-22 (4.38 g, 3.05 mmol, 60% purity, 1 eq) in DMF (32 mL) Petition 870260086043, dated 08 / 24 / 2026, pp. 158 / 389 153 / 328 a portion at 20 °C. The mixture was stirred at 20 °C for 1 h. The mixture was filtered and the collected resin was washed with DMF (25 mL x 3) and DCM (25 mL x 3) to provide the crude product 22 in CTC resin (3.7 g, 3.05 mmol, 99.96% yield, 52.7% purity) as a light yellow solid. LC-MS (ESI): RT = 0.716 min, m / z calculated for Ci5H20NeO5Na, 387.15 [M+Na]+; m / z found 387.1; LC-MS conditions: Method 13.

[558] To a solution of AA10 (2.85 g, 6.09 mmol, 2 eq) and DIEA (1.57 g, 12.18 mmol, 2.12 mL, 4 eq) in DMF (20 mL), HATU (2.32 g, 6.09 mmol, 2 eq) was added in a portion at 20 °C. The mixture was stirred at 20 °C for 0.2 h. Compound 22 (3.7 g, 3.05 mmol, 52.7% purity, 1 eq) was added and the mixture was stirred at 20 °C for 2 h. After completion, the reaction mixture was subjected to acid cleavage using an AcOH cocktail (20 mL, AcOH:TFE:DCM = 1:1:8) for 2 h. Then, the mixture was filtered and the collected resin was washed with DCM (5 mL x 3). The filtration was washed with H2O (10 mL x 3) and the combined aqueous layers were extracted with DCM (10 mL x 2). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to generate a residue, which was purified by C-18 reverse-phase chromatography (ISCO®; 40 g C-18® column, 0-60% ACN / H2O (0.1% AcOH) eluent gradient at 40 mL / min, 30 min with a total volume of 1.2 L). After lyophilization, AA10-AA9-AA8-OH (260 mg, 287.51 μNoO, yield of 9.44%, purity of 90%) was obtained as a whitish solid. LCMS (ESI): RT = 3,050 min, m / z calcd. for C44H48N9O7, 814.36, [M+H]+; m / z found 814.4; Conditions LC-MS: Method 13. Example 5. Synthesis (LPPS) of M2 in Tag2 5.1 Synthesis of Tag 2

[559] The synthetic route to make Tag2 is shown in Scheme 3 below. Scheme 3 Petition 870260086043, dated 08 / 24 / 2026, pp. 159 / 389 154 / 328 Tag 2-2a b““ Tag2-1 Tag2-2 Tag2-3 Tag2-4 Tag2 Reagents and conditions: a) C22H4sBr (2.2 eq.), K2CO3 (6 eq.), DMF / THF, 90 °C, 12 h, 91%; b) (4-methoxyphenyl)magnesium bromide (1 M, 3 eq.), THF, 70 °C, 12 h, 91%; c) FmocNH2 (2 eq.), MsOH (0.3 eq.), THF, 70 °C, 12 h, 86%; d) 20% piperidine in THF, 20 °C, 2 h, 96%. Total yield: 75.8%

[560] Treatment of 2,4-dihydroxybenzaldehyde (Tag2-1) with 2.2 eq. of 1-bromodocosane in the presence of potassium carbonate in DMF / THF produced a bis C22 alkyl substituted compound (Tag2- 2) The Grignard reaction of Tag2-2 with Grignard reagent (Tag2-2a), followed by nucleophilic substitution of alcohol (Tag2-3) with 9-fluorenylmethylcarbamate, yielded Tag2-4. Tag2 was obtained through a common Fmoc shielding of Tag2-4.

[561] Both the alcohol tag (Tag2-3) and the amine tag (Tag2) are novel tags designed for use in the production of short peptide acids and amides. The two hydrophobic C22 alkyl chains in Tag2-3 and Tag2 have retained the hydrophobicity of their TCPs, which can be precipitated in polar solvents during the synthesis process. Step a: Synthesis of 2,4-Di(docosoxy)benzaldehyde (Tag2-2) Tag2-1 ^22^45^1 (2.2 GO.), KoCOq (6 GO.), DMF / THF, 90 oC, 12 h, 91%; THE Tag2-2

[562] A mixture of 2,4-dihydroxybenzaldehyde (Tag2-1, 5 g, 36.20 mmol, 1 eq) and 1-bromo-docosane (31.02 g, 79.64 mmol, 2.2 eq) in DMF (100 mL) and THF (20 mL) K2CO3 (30.02 g, 217.20 mmol, 6 eq) was added and stirred at 90 °C for 12 h. The largest Petition 870260086043, dated 08 / 24 / 2026, p. 160 / 389 155 / 328 of the reagent was consumed and a new spot formed on TLC (PE / EtOAc = 5 / 1). The reaction mixture was poured into water (1000 mL), and the mixture was stirred for 1 h, then the precipitated solid was collected by filtration. The obtained solid was ground with acetone (1000 mL), collected by filtration and washed in methanol and dried under reduced pressure to give the desired compound Tag22 (27 g, crude) as a whitish solid. 1H NMR (400MHz, chloroform-d) δ = 10.34 (s, 1H), 7.80 (d, J=8.8 Hz, 1H),6.52 (dd, J=1.5, 8.8 Hz, 1H), 6.43 (d, J=1.9 Hz, 1H), 4.08 - 3.97(m, 4H), 1.89 - 1.73 (m, 4H), 1.52 - 1.44 (m, 4H), 1.26 (s,72H), 0.89 (t, J=6.7 Hz, 6H) ppm. Step b: Synthesis of (2,4-Bis(docosyloxy)phenyl)(4methoxyphenyl)methanol (Tag2-3) θ22Η45^0· Tag2-2 .-^^022^45 O (4-methoxyphenylimmagnesium bromide (1 M, 3 eq.), THF, 70°C, 12h, 91% Tag2-3

[563] To a solution of Tag2-2 (31 g, 41.04 mmol, 1 eq) in THF (300 mL) bromo-(4-methoxyphenyl)magnesium (Tag22a, 1 M, 123.13 mL, 3 eq) was added and the reaction mixture was stirred at 70 °C for 12 hours. TLC (PE:EtOAc = 10:1) showed that the reaction was complete. After cooling to room temperature, 1 N hydrochloric acid (100 mL) and THF (100 mL) were added to the reaction. Separated organic layers were washed with brine (50 mL x 2), dried over Na2SO4, filtered and concentrated under reduced pressure to provide a residue, which was triturated with ACN (150 mL) and MeOH (80 mL). The suspension was filtered and thoroughly washed with ACN (100 mL) and methanol (80 mL) to yield the product. Tag2-3 (36 g, 37.53 mmol, 91.43% yield, 90% pure) as a clear bitter solid.1H NMR (400MHz, chloroform-d) δ = 7.30 -7.27 (m, 2H), 7.17 - 7.00 (m, 1H), 6.90 - 6.77 (m,2H), 6.49 - 6.32 (m, 2H), 5.98 - 5.49 (m, 1H), 3.99 - 3.85 (m,4H), 3.85 - 3.70 (m, 4H), 3.53 - 3.35 (m, 2H), 1.80 - 1.68 (m,4H), Petition 870260086043, 08 / 24 / 2026, pág. 161 / 389 156 / 328 1.43 (br d, J=5.0 Hz, 4H), 1.26 (s, 72H), 0.89 (t, J=6.7 Hz, 6H) ,NH CLuFmoc C22H45 ppm. Step c: Synthesis of (9H-Fluoren-9-yl)methyl((2,4bis(docosiloxy)phenyl)(4-methoxyphenyl) methyl)carbamate (Tag2-4) I ^22^45 ll íl ^22^45 FmocNH2(2 eq.), MsOH (0.3 eq.), THF, 70 oC, 12 h, 86% C22H45 Tag2-3

[564] To a solution of 9H-fluoren-9-ylmethyl carbamate (10.77 g, 45.03 mmol, 1.2 eq) in THF (300 mL), Tag23 (36 g, 37.53 mmol, 90% purity, 1.0 eq) and MsOH (1.08 g, 11.26 mmol, 801.41 pL, 0.3 eq) were added, then the reaction mixture was stirred at 70 °C for 12 hours. TLC (PE:EtOAc = 10:1) confirmed the completion of the reaction. After evaporation to remove most of the solvent, the residue was triturated with 5% aqueous NaHCO3 (10 mL), MeOH (80 mL) and ACN (150 mL). The suspension was filtered and carefully washed sequentially with ACN (120 mL) and methanol (80 mL) to generate Tag2-4 (39 g, 32.36 mmol, 86.24% yield, 90% purity) as a light yellow solid. 1H NMR (400 MHz, Chloroform-d) δ = 7.85 - 7.69 (m, 2H), 7.68 - 7.50 (m, 2H) 4.47 - 4.35 (m, 2H), 4.25 (br t, J=7.0 Hz, 1H), 3.97 - 3.91 (m, 2H), 3.86 - 3.71 (m, 5H), 3.42 - 3.19 (m, 1H), 1.80 - 1.64 (m, 4H), 1.48-1.36 (m, 4H), 1.1.1.32-1.72 (H), 0.95-0.82 (m, 6H) ppm. Step d: Synthesis of (2,4-bis(Docosyloxy)phenyl)(4methoxyphenyl)methanamine (Tag2) II T Π Η Tυ22Η45 T | in| Tυ22Μ45 N|_| q 20% piperidine in THF, 20°C,o Fmoc' C22H45 2h, 96%2^22^45 Tag2-4 Tag2 Petition 870260086043, of 24 / 08 / 2026, p. 162 / 389 157 / 328

[565] To a solution of Tag2-4 (37 g, 30.70 mmol, 90% purity, 1 eq) in THF (240 mL) was added piperidine (51.73 g, 607.56 mmol, 60 mL, 19.79 eq) and the reaction mixture was stirred at 20 °C for 2 hours. TLC (PE:EtOAc = 10:1) showed that the reaction was complete. The mixture was added to ACN (800 mL), the resulting suspension was filtered and thoroughly washed with ACN (200 mL) and methanol (100 mL) to give Tag2 (30 g, 29.57 mmol, 96.31% yield, 85% purity) as a light yellow solid. LC-MS (Method 7): RT = 2.038 min, m / z calcd. for C58H101O3 845, 78 [M-NH3]+, found 845, 8. 1H NMR (400MHz, Chloroform-d) δ =7.29 (d, J=8.5 Hz, 2H), 7.16 - 7.10 (m,1H), 6.83 (d, J=8.8 Hz, 2H), 6.45 - 6.38 (m, 2H), 5.37 (s, 1H),3.95 - 3.85 (m, 4H), 3.79 (s, 3H), 1.77 - 1.71 (m, 4H), 1.48 -1.38 (m, 4H), 1.27 (s, 72H), 0.89 (s, 6H) ppm. 5.2 Tag2-M2 Synthesis

[566] Figure 3 and Table 6 describe the synthesis of M2 using Tag2. Tabela 6. Etapa # Reação de acoplamento de amida Interrupção De-Fmoc Produto aminoácido DIC HOAt propan- 1-amina 20% de piperidina em THF # MS (M+H)+ Rendimento ( %) 1 AA1 1,5 eq. 1,5 eq. 1,5 eq. 2 eq. 20 V Tag21AA 1065,92, [M+H] + 94,7 2 AA2 1,5 eq. 1,5 eq. 1,5 eq. 2 eq. 20 V Tag22AA 1430,11, [M+H] + 94,7 3 AA3 1,5 eq. 1,5 eq. 1,5 eq. 2 eq. 20 V Tag23AA 700,37 [M-Tag2- tBu+3H]+ 91,6 4 AA4 1,5 eq. 1,5 eq. 1,5 eq. 2 eq. 20 V Tag24AA 787,41 [M-Tag2- 2tBu+4H]+ 89,4 5 AA5 1,5 eq. 1,5 eq. 1,5 eq. 2 eq. 20 V Tag25AA 888,45, [M-Tag2- 3tBu+5H]+ 79,0 6 AA6 1,5 eq. 1,5 eq. 1,5 eq. 2 eq. 20 V Tag26AA 1067,53, [M-Tag23tBu+5H]+ 78,5 Petição 870260086043, de 24 / 08 / 2026, pág. 163 / 389 158 / 328 7 AA7 3 eq. 3 eq. 3 eq. 2 eq. 20 V Tag27AA 1168,58, [M-Tag24tBu+6H]+ 79,7 8 AA10 - AA9- AA8- OH 1,05 eq. HATU (1,2 eq.) / / / Tag2- 10AA 786,375 [M+2H]2+ / cliv agem M2 14,5 General procedure C for amide coupling and Fmoc deprotection in a single vessel to generate Tag2-nAA.

[567] To a solution of Tag2 or Tag2-(n-1)AA (1 eq.) and AAn (1.5 eq.) and HOAt (1.5 eq.) in DCM (20 V), DIC (1.5 eq.) was added in a portion at 20 °C. The mixture was stirred at 20 °C for 12 h. After completion, propan-1-amine (2 eq) was added and the mixture was stirred at 20 °C for 0.5 h. Then, 20% piperidine in THF (20 V) was added and the mixture was stirred at 20 °C for 1 h. TLC (PE:EtOAc = 3:1) showed that the reaction was complete. The mixture was triturated with ACN / MeOH = 3 / 1 (40 V * 2) to give the product Tag2-nAA as a light yellow solid, which was used in the next step directly without purification. Step 1: Synthesis of (2S)-2-Amino-N-((2,4 bis(docosyloxy)phenyl)(4-methoxyphenyl)methyl)-5-(3,5 dimethylphenyl)pentanamide (Tag2-1AA) The 'C22H45 AA1 VjQ NHFmoc I0ll I fu íl 'ί' 'C22H45 fí η C22H45 H2N'qr' γγ (yA (1) AA1 (1.5 eq.), DIC (1.5 eq.), HOAt (1.5 eq.), THF, 20 o XÁ °C, 12 h; (2) propargylamine (2 eq., 20 °C, 0.5 h; (3) 20% piperidine in THF, 20 °C, 2 h; Tag2 Tag2-1AA

[568] To a solution of Tag2 (6.5 g, 7.16 mmol, 95% purity, 1 eq), AA1 (4.76 g, 10.74 mmol, 1.5 eq) and HOAt (1.46 g, 10.74 mmol, 1.50 mL, 1.5 eq) in DCM (80 mL), DIC (1.36 g, 10.74 mmol, 1.66 mL, 1.5 eq) was added in a portion at 20 °C. The mixture was stirred at 20 °C for 12 h. After completion, propan-1-amine Petition 870260086043, dated 08 / 24 / 2026, page 164 / 389 159 / 328 (846.45 mg, 14.32 mmol, 1.18 mL, 2 eq) was added and the mixture was stirred at 20 °C for 0.5 h. Then, piperidine (16.65 g, 195.52 mmol, 19.31 mL, 27.31 eq) in THF (80 mL) was added and the mixture was stirred at 20 °C for 1 h. TLC (PE:EtOAc = 3:1) showed that the reaction was complete. The mixture was triturated with ACN / MeOH = 3 / 1 (150 mL * 2) to give Tag2-1AA (8.5 g, 6.78 mmol, 94.69% yield, 85% purity) as a light yellow solid, which was used directly in the next step without purification. LCMS (ESI): RT = 2.092 min, m / z calcd. for C71H121N2O4, 1065, 92, [M+H]+; m / z found 1065, 9; LCMS conditions: Method 7. Step 2: Synthesis of (2S)-2-((S)-2-Amino-3-(4'-(4azidobutoxy)-2'-ethyl-[1,1'-biphenyl]-4-yl)propanamido)-N-((2,4bis(docosyloxy)phenyl)(4-methoxyphenyl)methyl)-5-(3,5dimethylphenyl) Pentanamide (Tag2-2AA) Tag2-1AA (1) AA2 (1.5 eq.), DIC (1.5 eq.), HOAt (1.5 eq.), THF, 20 °C, 12 h; (2) propargylamine (2 eq., 20 °C, 0.5 h; (3) 20% piperidine in THF, 20 °C, 2 h;

[569] The reaction was carried out according to general procedure C for amide coupling and Fmoc deprotection in a single vessel using Tag2-1AA (3 g, 2.39 mmol, 85% purity, eq) and AA2 (2.18 g, 3.61 mmol, 1.51 eq). Crude Tag2-2AA (3.6 g, 2.27 mmol, 94.68% yield, 90% purity) was obtained as a light yellow solid. LCMS (ESI): RT = 2.225 min, m / z calculated for C92H144N6O6, 1430.11, [M+H]+; m / z found 1431.0; LC-MS conditions: Method 7. Step 3: Synthesis of (3S)-tert-Butyl 3-amino-4-(((2S)-3-(4'(4-azidobutoxy)-2'-ethyl-[1,1'-biphenyl]-4-yl)-1-(((2S)-1(((2,4-bis(docosyloxy)phenyl)(4- methoxyphenyl)methyl)amino)-5(3,5-dimethylphenyl)-1-oxopentan-2-yl)amino)-1-oxopropan-2yl)amino)-4-oxobutanoate (Tag2-3AA) Petition 870260086043, dated 08 / 24 / 2026, pp. 165 / 389 160 / 328 (1) AA3 (1.5 eq.), DIC (1.5 eq.), HOAt (1.5 eq.), THF, 20 °C, 12 h; (2) propargylamine (2 eq., 20 °C, 0.5 h; (3) Tag2-2AA AA3 >r YT ° O NHFmoc 20% piperidine in THF, 20 °C, 2 h;

[570] The reaction was carried out according to the general procedure C for amide coupling and Fmoc deprotection in a single vessel using Tag2-2AA (3.8 g, 2.39 mmol, 90% purity, 1 eq) and AA3 (1.48 g, 3.59 mmol, 1.5 eq). Crude Tag2-3AA (3.9 g, 2.19 mmol, 91.66% yield, 90% purity) was obtained as a light yellow solid. LCMS (ESI): RT = 3,660 min, m / z calculated for C38H50N7O6, 700.37 [M-anchor-tBu+3H]+; (anchor = C58H101O3, MS = 845.8); m / z found 700.4; LC-MS conditions: Method 7. (anchor = Tag2). Step 4: Synthesis of (3S)-tert-Butyl 3-((S)-2-amino-3-(tert butoxy)propanamido)-4-(((2S)-3-(4'-(4-azidobutoxy)-2'-ethyl[1,1'-biphenyl]-4-yl)-1-(((2S)-1-(((2,4bis(docosyloxy)phenyl)(4-methoxyphenyl) methyl)amino)-5-(3,5dimethylphenyl)-1-oxopentan-2-yl)amino)-1-oxopropan-2-yl)amino) 4-oxobutanoate (Tag2-4AA) (1) AA4 (1.5 eq.), DIC (1.5 eq.), HOAt (1.5 eq.), THF, 20 °C, 12 h; (2) propargylamine (2 eq., 20 °C, 0.5 h; (3) 20% piperidine in THF, 20 °C, 2 h; AA4 Tag2-4AA

[571] The reaction was carried out according to the general procedure C for amide coupling and Fmoc deprotection in a single vessel using Tag2-3AA (3.9 g, 2.19 mmol, 90% purity, 1 eq) and AA4 (1.26 g, 3.29 mmol, 1.5 eq). Crude Tag2-4AA (3.8 g, 1.96 mmol, 89.44% yield, 90% purity) was obtained as a light yellow solid. LCMS (ESI): RT = 3,540 min, m / z calculated for C41H55N8O8, 787.41 [M-anchor-2tBu+4H]+; (anchor=C58H101O3, MS =845.8); m / z found 787.5; LCMS conditions: Method 7. (anchor = Tag2). Petition 870260086043, of 24 / 08 / 2026, p. 166 / 389 161 / 328 Step 5: Synthesis of (3S)-terc-Butyl 3-((S)-2-(((2S,3R)-2Amino-3-(terc-butoxy)butanoyl)oxi)-3-(terc butoxy)propanamide)-4-(((2S)-3-(4'-(4-oxybutoxy-2') [1,1'-biphenyl]-4-yl)-1-(((2S)-1-(((2,4 bis(docosyloxy)phenyl)(4-methoxyphenyl)methyl)amino)-5-(3,5 dimethylphenyl)-1-oxopentane-2-yl)amino)-1-oxopropane-2-yloxybutano)4-ato-ato (Tag2-5AA) Tag2-4AA AA5 (1) AA5 (1.5 equiv), DIC (1.5 equiv), HOAt (1.5 equiv), THF, 20 °C, 12 h; (2) propargylamine (2 equiv., 20 °C, 0.5 h; (3) 20% piperidine in THF, 20 °C, 2 h;

[572] The reaction was carried out according to the general procedure C for amide coupling and Fmoc deprotection in a single vessel using Tag2-4AA (3.8 g, 1.96 mmol, 90% purity, 1 eq) and AA5 (1.17 g, 2.94 mmol, 1.5 eq). Crude Tag2-5AA (3.1 g, 1.55 mmol, 78.99% yield, 95% purity) was obtained as a light yellow solid. LCMS (ESI): RT = 3,510 min, m / z calculated for C45H62N9O10, 888.45, [M-anchor-3tBu+5H]+; (anchor=C58H101O3, MS =845.8); m / z found 888.5; LCMS conditions: Method 7. (anchor = Tag2). Step 6: Synthesis of (3S)-tert-Butyl 3-((S)-2-((2S,3R)-2 ((S)-2-Amino-3-(2-fluorophenyl)-2-methylpropanamido)-3-(tert-butoxy)butanamido)-3-(tert-butoxy)propanamido)-4-(((2S)-3-(4'(4-azidobutoxy)-2'-ethyl-[1,1'-biphenyl l]-4-yl)-1-(((2S)-1(((2,4-bis(docosyloxy)phenyl)(4-methoxyphenyl)methyl)amino)-5(3,5-dimethylphenyl)-1-oxopentan-2-yl)amino)-1-oxopropan-2yl)amino)-4-oxobutanoate (Tag2-6AA) (1) AA6 (1.5 eq.), DIC (1.5 eq.), HOAt (1.5 eq.), THF, 20 °C, 12 h; (2) propargylamine (2 eq., 20 °C, 0.5 h; (3) 20% piperidine in THF, 20 °C, 2 h; AA6

[573] The reaction was carried out according to the general procedure C for amide coupling and Fmoc deprotection in a Petition 870260086043, dated 08 / 24 / 2026, page 167 / 389 162 / 328 single container using Tag2-5AA (1.5 g, 749.31 μmol, 95% purity, 1 eq) and AA6 (471.44 mg, 1.12 mmol, 1.5 eq). Tag2-6AA (1.36 g, 588.20 μmol, 78.50% yield, 90% purity) was obtained as a light yellow solid. LCMS (ESI): RT = 3, 726 min, m / z calculated for C55H72FN10O11, 1067.53, [M-anchor-3tBu+5H]+; (anchor = C58H101O3, MS = 845.8); m / z found 1067.6; Conditions LC-MS: Method 7. (anchor = Tag2). Step 7: Synthesis of (4R,5S,8S,11S,14S,17S)-terc-Butyl 5Amino-17-(((2S)-3-(4'-(4-azidobutoxy)-2'-ethyl-[1,1'-biphenyl]4-yl)-1-(((2S)-1-(((2,4-bis(docosyloxy)phenyl)(4-methoxyphenyl) methyl)amino)-1-oxo-5-(m-tolyl)pentane-2-yl)amino)-1-oxopropan2-yl)carbamoyl)-11-(CAN-1-(terc-butoxy)ethyl)-14-(ter cbutoxymethyl)-8-(2-fluorobenzyl)-2,2,4,8-tetramethyl-6,9,12,15tetraoxo-3-oxa-7,10,13,16-tetraazanonanodecane-19-oato (Tag2-7AA) (1) AA7 (3 equiv), DIC (3 equiv), HOAt (3 equiv), DCM (8 mL), THF (5 mL), 20 °C, 12 h; (2) propargylamine (2 equiv., 20 °C, 0.5 h; (3) 20% piperidine in THF, 20 °C, 2 h;

[574] The reaction was carried out according to the general procedure C for amide coupling and Fmoc deprotection in a single vessel using Tag2-6AA (0.7 g, 302.75 μmol, 90% purity, 1 eq) and AA7 (360.99 mg, 908.25 μmol, 3 eq). Crude Tag2-7AA (0.6 g, 241.27 μmol, 79.69% yield, 90% purity) was obtained as a light yellow solid. LCMS (ESI): RT = 3.977 min, m / z calculated for C59H79FN11O13, 1168.58, [M-anchor4tBu+6H]+; (anchor = C58H101O3, MS = 845.8); m / z found 1168.5; LC-MS conditions: Method 7 (anchor = Tag2) (filtration was very slow and it was difficult to collect solid particles due to poor precipitate). Step 8: Synthesis of (3S)-4-[[(1S)-1-[[4-[4-(4-Azidobutoxy)2-ethyl-phenyl]phenyl]methyl]-2-[[(1S)-1-carbamoyl-4-(3,5dimethylphenyl)bu til]amino]-2-oxo-ethyl]amino]-3-[[(2S)-2[[(2S,3R)-2-[[(2S)-3-(2-fluorophenyl)-2-[[(2S,3R)-3-hydroxy-2Petition 870260086043, of 08 / 24 / 2026, p. 168 / 389 163 / 328 [[2-[[(2S)-2-[[3-[2-(1H-imidazol-5-il)etilamino]-2,2-dimetil3-oxo-propanoil]amino]-3-(1H-tetrazol-5-il)propanoil]amino] Ácido acetil]amino]butanoil]amino]-2-metil-propanoil]amino]-3hidroxi-butanoil]amino]-3-hidroxi-propanoil]amino]-4-oxobutanoico (M2) o ,™0A / 0 0 I 0n-t^naan\.ii^ohT« UH HoN„ ο ο Λ ooo / 7 o AA10-AA9-AA8-OH N ,,. IIlHllUfllUllUl ------------------------- 'X'il'l »0Τ' fj T'B'T Vn0(1) AA10-AA9-AA8-OH (1,0 eq.), HATU / ζ) '° pT (1,2 eq), DMF / DCM=1 / 2, 20 °C, 12 h; (2) Coquetel de TFA (TFA:Etil Fenil Sulfeto:H2O= 95:2,5:2,5), 20 °C, 2 h; 14.5%M2

[575] To a solution of the reagents AA10-AA9-AA8-OH (216.01 mg, 238.86 μmol, 90% purity, 1.1 eq) and Tag2-7AA (540 mg, 217.14 μmol, 90% purity, 1 eq) in DMF (2 mL) and DCM (6 mL), HATU (99.08 mg, 260.57 μmol, 1.2 eq) was added in a portion at 20 °C. The mixture was stirred at 20 °C for 2 h. LCMS showed that the reaction was completely converted. The mixture was subjected to acid cleavage using a TFA cocktail (14 mL, TFA:Ethyl Phenyl Sulfide:H2O = 95:2.5:2.5) for 50 min. The reaction mixture was filtered, and the filtrate was extracted with water / ACN=4 / 1 (150 mL) and extracted with PE (20 mL*2). The combined aqueous layers were lyophilized to generate a residue, which was purified by prepHPLC (column: Welch Xtimate C18 100*40mm*3um; mobile phase: [water (TFA)-ACN]; B%: 28%-58%, 12 min condition) to generate the product. M2 (50 mg, 31.58 μmol, 14.54% yield, 99.27% ​​purity) as a white solid. LCMS (ESI): RT = 3.910 min, m / z calculated for C75H101FN20O17, 786.375 [M+H]+; m / z found 786.8; LC-MS conditions: Method 7. HPLC: RT = 4.86 min. HPLC conditions: Mobile phase: 1.0% ACN in water (0.1% TFA) to 5% ACN in water (0.1% TFA) in 1 minute; then 5% ACN in water (0.1% TFA) to 100% ACN (0.1% TFA) in 5 minutes; maintain at 100% ACN (0.1% TFA) for 2 minutes; return to 1.0% ACN in water (0.1% TFA) in 8.01 minutes and maintain for two minutes. Flow rate: 1.2 ml / min. Speaker: Ultimate XB-C18, 3 pm, 3.0 x 50 mm. Example 6. Synthesis (LPPS) of M2 in Tag3 Petition 870260086043, dated 08 / 24 / 2026, pp. 169 / 389 164 / 328 6.1 Tag3 Synthesis

[576] The synthetic route to make Tag3 is shown in the Scheme Scheme 4 Tag3-Í Tag 3-1

[577] Reagents and conditions: a) CeeíhsBr (2.2 eq.), K2CO3 (6 eq.), DMF / THF, 90 °C, 12 h, 99%; b) NH2OH.HC1 (3 eq.), Et3N (5 eq.), toluene (20 mL), 100 °C, 12 h, 93%; c) DIBALH (3.0 eq.), toluene (30 mL), 1000C, 12 h, 91%; d) 2—[4—[(2,4-dimethoxyphenyl)-(9H-fluoren-9-ylmethoxycarbonylamino)methyl]phenoxy]acetic acid (1.5 eq.), DIC (1.5 eq.), HOAt (1.5 eq.), DCM (2 mL), 20°C, 12 h, 68%; e) 20% piperidine in THF, 20°C, 2 h, 99%. Total yield: 56.4%.

[578] Bis-alkylation of 2,4-dihydroxybenzaldehyde with C22 alkyl bromide, followed by treatment of Tag3-1 with the same equivalent of hydroxylamine hydrochloride in the presence of TEA in toluene, yielded the oxime product Tag3-2. DIBAL reduction of Tag3-2 to the amine Tag3-3 and subsequent coupling with the acid Tag3-3a yielded the amide Tag3-4. The reagent Tag3-3a (CAS: 145069-56-3, Rink Amide Linker.), 4-[(2,4-dimethoxyphenyl)(fmoc-amino)methyl]phenoxyacetic acid, is commonly used in solid-phase syntheses for the preparation of primary C-terminal amide peptides. Finally, Fmoc deprotection of Tag3-4 yielded Tag3. Step a: Synthesis of 2,4-Di(docosoxy)benzaldehyde (Tag3-1) Petition 870260086043, dated 08 / 24 / 2026, pp. 170 / 389 165 / 328a HO-^^OH C22H45Br (2.2 eq.), K2CO3(6 eq.), c22h45.oÁ^o,c22h45 DMF / THF, 90°C, 12h, 99% Tag3-SM Tag3-1

[579] To a mixture of 2,4-dihydroxybenzaldehyde (2 g, 14.48 mmol, 1 eq) and 1-bromodocosane (12 g, 30.81 mmol, 2.13 eq) in DMF (50 mL), K2CO3 (12.01 g, 86.88 mmol, 6 eq) was added and stirred at 90 °C for 12 h. Most of the reagent was consumed and a new spot formed on the TLC (PE / EtOAc = 5 / 1). After the reaction was complete, the reaction mixture was poured into water (500 mL), stirred for 1 h, and the precipitated solid was collected by filtration. The solid obtained was ground with acetone (200 mL), collected by filtration, and washed with methanol. After filtration, the obtained solid was dried under reduced pressure to yield the compound in question as a whitish solid. The resulting solid was ground again with PE (100 mL) and collected by filtration. The desired compound, Tag3-1 (10.9 g, 14.43 mmol, 99.67% yield, n / a purity), was obtained as a whitish solid.1H NMR (400MHz, chloroform-d) δ = 10.33 (s, 1H), 7.80 (d, J=8.6 Hz, 1H), 6.52 (d, J=8.8 Hz, 1H), 6.42 (d, J=2.1 Hz, 1H), 4.08 - 3.97 (m, 4H), 1.89 - 1.69 (m, 4H), 1.52 - 1.42 (m, 4H), 1.26 (s, 72H), 0.89 (t, J=6.8 Hz, 6H) ppm. Step b: Synthesis of (1E)-2,4-Di(docosoxy)benzaldehyde Oxime (Tag3-2) Tag3-1 b NH2OH.HCI (3 eq.), Et3N (5 eq.), toluene (20 mL), 100 °C, 12 h, 93%H%o,c22h45 Tag3-2

[580] To a mixture of Tag3-1 (6.5 g, 8.61 mmol, 1 eq) in toluene (90 mL), NH2OH.HCl (5.98 g, 86.06 mmol, 10 eq) and Et3N (8.71 g, 86.06 mmol, 11.98 mL, 10 eq) were added, and the reaction mixture was stirred at 100 °C for 12 h. Most of the reagent was consumed and a new spot with greater polarity was formed. Petition 870260086043, dated 08 / 24 / 2026, pp. 171 / 389 166 / 328 in TLC (PE / EtOAc = 10 / 1). After completion, the reaction mixture was cooled to 20 °C and poured into ACN (300 mL). The precipitated solid was then collected by filtration and washed with methanol. The resulting solid was ground with ACN (300 mL) and collected by filtration. After filtration, the solid was dried under reduced pressure to yield the title compound as a brown solid. The desired compound Tag3-2 (6.2 g, 8.05 mmol, 93.53% yield) was obtained as a brown solid. 1H NMR (400 MHz, Chloroform-d) δ = 8.46 (s, 1H), 7.65 (d, J = 8.5 Hz, 1H), 6.51 - 6.41 (m, 2H), 4.03 - 3.91 (m, 4H), 1.87 - 1.71 (m, 4H), 1.50 - 1.42 (m, 4H), 1.27 (s, 72H), 0.89 (t, J = 6.8 Hz, 6H) ppm. Step 3: Synthesis of [2,4-Di(docosoxy)phenyl]methanamine (Tag33) NO C í| η ^22H45h2nYA ^Ào-c22h45DIBALH (3.0 eq.), toluene (30 mL), °'c22h45 100 °C, 12 h, 91%22 45 Tag3-2 Tag3-3

[581] To a mixture of Tag3-2 (5 g, 6.49 mmol, 1 eq) in THF (50 mL), DIBALH (1 M, 19.47 mL, 3 eq) was added dropwise at 0 °C and the reaction mixture was stirred at 90 °C for 12 h. Most of the reagent was consumed and a new spot with low polarity was formed on the TLC (PE / EtOAc = 10 / 1). The reaction mixture was poured into a saturated solution of sodium tartrate tetrahydrate (100 mL), and the precipitated solid was collected by filtration and washed with methanol. The resulting solid was ground with ACN (30 mL) was collected by filtration. After filtration, the solid obtained was dried under reduced pressure to generate the compound of title Tag3-3 (4.5 g, 5.95 mmol, 91.66% yield) as a whitish solid. 1H NMR (400 MHz, chloroform-d) δ = 6.61 6.29 (m, 3H), 4.14 - 3.65 (m, 6H), 2.84 (br s, 2H), 1.83 - 1.73 (m, 4H), 1.4 - 1.5 (m, 4H), 1.27 (br s, 72H), 0.89 (br t, J = 6.5 Hz, 6H) ppm. Step 4: Synthesis of 9H-Fluoren-9-ylmethyl N-[[4-[2-[[2,4]] Petition 870260086043, dated 08 / 24 / 2026, p. 172 / 389 167 / 328 di(docosoxy)phenyl]methylamino]-2-oxo-ethoxy]phenyl]-(2,4dimethoxyphenyl)methyl]carbamate (Tag3-4) d Tag3-2A (1.5 eq.), DIG (1.5 eq.), H0At (1.5 eq.), DCM (2 mL), 20 oC, 12 h, 68% Tag3-4

[582] For a solution of Tag3-3 (2 g, 2.64 mmol, 1 eq) and acid 2-[4-[(2,4-dimethoxyphenyl)-(9H-fluoren-9-ylmethoxycarbonylamino)methyl]phenoxy]acetic acid Tag3-3a (2.14 g, 3.97 mmol, 1.5 eq) in DCM (20 mL) was added to DIC (500.58 mg, 3.97 mmol, 614.21 pL, 1.5 eq) and HOAt (539.89 mg, 3.97 mmol, 554.87 pL, 1.5 eq) and the resulting mixture was stirred at 20 °C for 2 h. Most of the reagent was consumed and new points with high polarity were formed in TLC (PE / EtOAc = 3 / 1). ACN (100 mL) was added to the reaction mixture, and the resulting suspension was filtered and washed with MeOH (30 mL x 2) to yield a whitish solid. The obtained solid was ground with ACN (30 mL) and collected by filtration. After filtration, the obtained solid was dried under reduced pressure to yield the compound of title Tag3-4 (2.3 g, 1.80 mmol, yield of 68.06%) as a whitish solid. 1H NMR (400MHz, Chloroform-d) δ = 7.77 (br d, J =7.1 Hz, 2H), 7.60 (br d, J =6.8 Hz, 1H), 7.49 -7.27 (m, 5H), 7.22 - 7.02 (m, 4H), 6.95 - 6.69 (m, 2H), 6.57 -6.36 (m, 4H), 6.02 (br d, J =8.6 Hz, 1H), 5.75 (br d, J =7.6 Hz, 1H), 4.55 - 4.14 (m, 5H), 4.08 - 3.66 (m, 10H), 4.08 - 3.63 (m, 1H), 1.95 - 1.67 (m, 4H), 1.54 - 1.41 (m, 4H), 1.27 (s, 72H),0.89 (t, J = 6.8 Hz, 6H) ppm. Step 5: Synthesis of 2-[4-[Amino-(2,4dimethoxyphenyl)methyl]phenoxy]-N-[[2,4di(docosoxy)phenyl]methyl]acetamide (Tag3) Petition 870260086043, dated 08 / 24 / 2026, pp. 173 / 389 168 / 328 20% piperidine in THF, 20°C, 2h, 99% Tag3-4 C22H45 Tag3

[583] For a solution of Tag3-4 (2.2 g, 1.72 mmol, 1 eq) in THF (20 mL) was added to piperidine (6.90 g, 81.01 mmol, 8 mL, 47.05 eq) and the resulting mixture was stirred at 20 °C for 2 h. Most of the reagent was consumed and new points with high polarity were formed in TLC (PE / EtOAc = 9 / 1). LCMS showed that the desired mass was detected. ACN (100 mL) was added to the reaction solution and the resulting suspension was filtered and washed with MeOH (30 mL x 2) to give a whitish solid. The obtained solid was ground with ACN (20 mL) and the solid was collected by filtration. The obtained solid was dried under reduced pressure to give the titrant compound Tag3 (1.8 g, 1.71 mmol, 99.04% yield) as a whitish solid. LCMS (ESI): RT = 2.055 min, calculated mass for C68H114N2O6H 1055, 9 [M+H]+, C68H112NO6+ 1038.8 [M-NH2P, m / z found 1038.8 [M-NH2P; LCMS Condition: Method 12. 1H NMR (400MHz, Chloroform-d) δ = 7.22 (br d, J = 8.5 Hz, 1H), 7.16 - 7.04 (m, 2H), 6.84 - 6.67 (m, 2H), 6.52 (d, J =2.3Hz, 1H), 6.49 - 6.29 (m, 4H), 5.36 (s, 1H),4.43 - 4.24 (m, 1H), 4.05 - 3.85 (m, 5H), 3.82 - 3.70 (m, 6H),3.19 (s, 2H), 1.83 - 1.75 (m, 4H), 1.26 (s, 76H), 0.90 - 0.87 (m,6H) ppm. 6.2 Tag3-nAA Synthesis

[584] Figure 4 and Table 7 below describe the synthesis of M2 using Tag3. Table 7 Coupling reaction of Fmoc Amino acid product DIC HOAt Yield Step # 20% piperidine in THF Yield Yield 9. % AA1 1.5 eq. 1.5 eq. 1.5 eq. 78.0% g 30 V Tag31AA 1259.0 [M+H]+ 95.0 Petition 870260086043, dated 08 / 24 / 2026, page 174 / 389 169 / 328 AA2 1.5 eq. 1.5 eq. 1.5 eq. 63.0% i 30 V Tag3- 2AA 585.3 [MTag3+2H] + 97.0 AA3 1.5 eq. 1.5 eq. 1.5 eq. 74.0% k 20 V Tag3- 3AA 700.37 [M-Tag3- tBu+3H]+ 89.0 AA4 1.5 eq. 1.5 eq. 1.5 eq. 89.0% m 20 V Tag3- 4AA 787.41, [M-Tag32tBu+4H] + 91.0 AA5 1.5 eq. 1.5 eq. 1.5 eq. 90.0% N-FmocTag 3-5AA 1110.52, [M-Tag33tBu+5H] + total yield to make Tag3-5AA 21.7 General procedure D for amide coupling to generate NFmoc-Tag3-nAA

[585] To a solution of Tag3 or Tag3-(n-1)AA (1 eq.) and AAn (1.5 eq.) in DCM (20 V) were added DIC (1.5 eq.) and HOAt (1.5 eq.), then the resulting mixture was stirred at 20 °C for 2 h. Most of the reagent was consumed and new spots with high polarity formed on TLC (PE / EtOAc = 3 / 1). A small sample was collected and piperidine was added to it to remove the Fmoc group. The sample was checked by LCMS, which showed that the desired mass was detected. ACN (80 V) was added to the reaction solution and the resulting suspension was filtered and washed with MeOH (30 V x 2) to provide a whitish solid. The obtained solid was ground with ACN (20 V) and the solid was collected by filtration. After filtration, the obtained solid was dried under reduced pressure to generate the titrant compound N-Fmoc-Tag3-nAA as a whitish solid. General procedure E for Fmoc deprotection to generate Tag3-nAA:

[586] A solution of N-Fmoc-Tag3-nAA (1 eq.) in 20% piperidine in THF (10 V) was stirred at 20 °C for 1 h. Most of the reagent was consumed and new spots formed in Petition 870260086043, dated 08 / 24 / 2026, pp. 175 / 389 170 / 328 TLC (PE / EtOAc = 9 / 1). LCMS showed that the desired mass was detected. ACN (100 V) was added to the reaction solution and the resulting suspension was filtered and washed with MeOH (30 V x 2) to give the product. The solid obtained was ground with ACN (20 V) and collected by filtration. The title compound, Tag3-nAA, was obtained as a whitish solid. Step f: Synthesis of 9H-Fluoren-9-ylmethyl N-[(1S)-1-[[[4-[2[[2,4-di(docosoxy)phenyl]methylamino]-2-oxo-ethoxy]phenyl]-(2,4-dimethoxyphenyl)methyl]carbamoyl]-4-(3,5-dimethylphenyl)butyl]carbamate (N-Fmoc-Tag3-1AA)

[587] The reaction was carried out using general procedure D for amide coupling using Tag3 (1 g, 947.29 μmol, 1 eq) and AA1 (630.23 mg, 1.42 mmol, 1.5 eq) in DCM (20 mL). N-FmocTag3-1AA (1.1 g, 742.66 μmol, yield 78.40%) was obtained as a whitish solid. LCMS (ESI): RT = 2.252 min, calculated mass for C81H131N3O7H 1259.9, m / z found 1260.0 [M- Fmoc+H]+; LCMS condition: Method 12.

[588] 1H NMR (400MHz, Chloroform-d) δ = 7.83 - 7.50 (m,4H), 7.45 - 7.26 (m, 5H), 7.12 - 6.61 (m, 9H), 6.55 - 6.17 (m,4H), 5.55 - 5.27 (m, 1H), 4.54 - 4.09 (m, 6H), 4.06 - 3.70 (m,8H), 3.69 - 3.55 (m, 3H), 3.49 (br s, 6H), 3.17 (br s, 2H), 2.50 (br s, 2H), 2.27 (br s, 6H), 2.01 (s, 2H), 1.27 (br s, 76H), 0.910.87 (m, 6H) ppm. Step g: Synthesis of (2S)-2-Amino-N-[[4-[2-[[2,4-di(docosoxy)phenyl]methylamino]-2-oxo-ethoxy]phenyl]-(2,4-dimethoxyphenyl)methyl]-5-(3,5-dimethylphenyl)pentanamide (Tag3-1AA) Petition 870260086043, dated 08 / 24 / 2026, pp. 176 / 389 171 / 328 N-Fmoc-Tag3-1AA

[589] The reaction was carried out for deprotection of Fmoc μηοΐ, 1 eq) in THF (10 yield of 95.30%) was (using mL). obtained using the general procedure E N-Fmoc-Tag3-1AA (1 g, 675, 15 Tag3-1AA (0.81 g, 643.41 μNοΐ, as a whitish solid. LCMS (ESI): RT = 6.848 min, mass calculated for C81H131N3O7H 1258.9 [M+H]+, m / z found 1259.0 [M+H]+; LCMS condition: Method 12. Step h: Synthesis of 9H-Fluoren-9-ylmethyl N-[(1S)-1-[[4-[4(4-azidobutoxy)-2-ethyl-phenyl] phenyl]methyl]-2-[[(1S)-1-[[[4-[2[[2,4-di(docosoxy)phenyl]methylamino]-2-oxo-ethoxy] phenyl]-(2,4dimethoxyphenyl)methyl]carbamoyl]-4-(3,5dimethylphenyl)butyl]amino]-2-oxo-ethyl]carbamate (N-Fmoc-Tag32AA) for amide coupling using Tag3-1AA (0.6 g, 476.60 μN, 1 eq) and AA2 (432.30 mg, 714.90 μN, 1.5 eq). N-Fmoc-Tag3-2AA 5 (0.56 g, 303.43 μN, 63.66% yield) was obtained as a whitish solid. LCMS (ESI): RT = 6.048 min, calculated mass for C49H54N6O5Na 829.4, m / z found 829.4 [M-Rink amide anchor + 2H]+; Rink amide = C17H18O4, anchor = C51H97NO2; LC-MS conditions: Method 7.

[591] 1H NMR (400MHz, Chloroform-d) δ = 7.75 (br d, J = 6.3 Petition 870260086043, dated 08 / 24 / 2026, pp. 177 / 389 172 / 328 Hz, 2H), 7.57 - 7.28 (m, 5H), 7.24 - 6.89 (m, 10H), 6.86 -6.62 (m, 5H), 6.54 - 6.31 (m, 5H), 6.20 (br s, 1H), 5.27 (br s, 1H), 4.53 - 4.07 (m, 7H), 4.06 - 3.53 (m, 12H), 3.40 (br t, J =6.3 Hz, 2H), 3.17 (br d, J =7.3 Hz, 2H), 2. 64 - 2.45 (m, 4H),2.22 (br d, J = 3.3 Hz, 6H), 1.95 - 1.71 (m, 8H), 1.27 (s, 82H), 1.06 (br t, J = 7.2 Hz, 3H), 0.90 - 0.87 (m, 6H) ppm. Step i: Synthesis of (2S)-2-((S)-2-Amino-3-(4'-(4azidobutoxy)-2'-ethyl-[1,1'-biphenyl]-4-yl)propanamido)-N-((4(2-((2,4-bis (docosyloxy)benzyl)amino)-2-oxoethoxy)phenyl)(2,4dimethoxyphenyl)methyl)-5-(3,5-dimethylphenyl)pentanamide (Tag3-2AA) N-Fmoc-Tag3-2AA Tag3-2AA

[592] The reaction was carried out using the general procedure E for deprotection of Fmoc using N-Fmoc-Tag3-2AA (400 mg, 216.73 μNoO, 1 eq), Tag3-2AA (380 mg, 210.67 μNoO, 97.20% yield, 90% purity) as a light yellow solid was obtained. LC-MS conditions: Method 7. Step j: Synthesis of (3S)-tert-Butyl 3-((((9H-Fluoren-9yl)methoxy)carbonyl)amino)-4-(((2S)-3-(4'-(4-azidobutoxy)-2'ethyl-[1,1'-biphenyl]-4-yl)-1-(((2S)-1-(((4-(2-((2,4bis(docosyloxy)b enzyl)amino)-2-oxoethoxy)phenyl)(2,4dimethoxyphenyl)methyl)amino)-5-(3,5-dimethylphenyl)-1-oxopentan-2yl)amino)-1-oxopropan-2-yl)amino)-4-oxobutanoate (N-Fmoc-Tag33AA) Tag3-2AA

[593] The reaction was carried out using the general procedure D for amide coupling using Tag3-2AA (380 mg, 210.67 μmol, Petition 870260086043, dated 08 / 24 / 2026, pp. 178 / 389 173 / 328 90% purity, 1 eq) and AA3 (130.02 mg, 316.01 μNoO, 1.5 eq). NFmoc-Tag3-3AA (350 mg, 156.19 μNoO, 74.14% yield, 90% purity) was obtained as a light yellow solid. LCMS (ESI): RT = 5, 542 min, m / z calcd. For C53H60N7O8, 922.44, [M-Rink amide anchor-tBu+3H]+; Rink amide = C17H18O4, anchor = C51H97NO2; m / z found 922.3; LC-MS conditions: Method 7. Step k: Synthesis of (3S)-tert-Butyl 3-Amino-4-(((2S)-3-(4'(4-azidobutoxy)-2'-ethyl-[1,1'-biphenyl]-4-yl)-1-(((2S)-1-(((4(2-((2,4-bis(docosyloxy)benzyl)amino)-2-oxoethoxy)phenyl)(2,4dimethoxyphenyl) methyl)amino)-5-(3,5-dimethylphenyl)-1-oxopentan-2yl)amino)-1-oxopropan-2-yl)amino)-4-oxobutanoate (Tag3-3AA) N-Fmoc-Tag3-3AA Tag3-3AA

[594] The reaction was carried out using the general procedure E for deprotection of Fmoc using N-Fmoc-Tag3-3AA (350 mg, 156.19 μmol, 90% purity, 1 eq). Tag3-3AA (280 mg, 140.43 μmol, 89.91% yield, 90% purity) was obtained as a light yellow solid. LCMS (ESI): RT = 3.810 min, m / z calcd. For C38H50N7O6, 700.37, [M-Rink amide-anchor-tBu+3H]+; Rink amide = C17H18O4, anchor = C51H97NO2; m / z found 700.3; LC-MS conditions: Method 7. Step I: Synthesis of (3S)-tert-Butyl 3-((S)-2-((((9H-Fluoren9-yl)methoxy)carbonyl)amino)-3-(tert-butoxy)propanamido)-4(((2S)-3-(4'-(4-azidobutoxy)-2'-e til-[1,1'-biphenyl]-4-yl)-1(((2S)-1-(((4-(2-((2,4-bis(docosyloxy)benzyl)amino)-2oxoethoxy)phenyl)(2,4-dimethoxyphenyl) methyl)amino)-5-(3,5dimethylphenyl)-1-oxopentan-2-yl)amino)-1-oxopropan-2-yl)amino)4-oxobutanoate (N-Fmoc-Tag3-4AA) Petition 870260086043, dated 08 / 24 / 2026, pp. 179 / 389 174 / 328

[595] The reaction was carried out using the general procedure D for amide coupling using Tag3-3AA (280 mg, 140.35 μηοΐ, 90% purity, 1 eq) and AA4 (80.72 mg, 210.52 μmol, 1.5 eq). NFmoc-Tag3-4AA (300 mg, 124.94 μmol, 89.02% yield, 90% purity) was obtained as a light yellow solid. LCMS (ESI): RT = 5.337 min, m / z calcd. for C56H65N8O10, 1009.47, [M-Rink amide anchor-2tBu+4H]+; Rink amide = C17H18O4, anchor = C51H97NO2; m / z found 1009.4; LC-MS conditions: Method 7. Step m: Synthesis of (3S)-tert-Butyl 3-((S)-2-Amino-3-(tertbutoxy)propanamido)-4-(((2S)-3-(4'-(4-azidobutoxy)-2'-ethyl[1,1'-biphenyl]-4-yl)-1-(((2S)-1-(((4-(2-((2,4bis(docosyloxy)be nzil)amino)-2-oxoethoxy)phenyl)(2,4dimethoxyphenyl)methyl)amino)-5-(3,5-dimethylphenyl)-1-oxopentan-2yl)amino)-1-oxopropan-2-yl)amino)-4-oxobutanoate (Tag3-4AA) N-Fmoc-Tag3-4AA Tag3-4AA

[596] The reaction was carried out using the general procedure E for Fmoc deprotection, using N-Fmoc-Tag3-4AA (280 mg, 116.67 μmol, 90% purity, 1 eq). NTag3-4AA (230 mg, 106.83 μmol, 91.56% yield, 90% purity) was obtained as a light yellow solid. LC-MS conditions: Method 7. Step n: Synthesis of (5S,8S,11S)-tert-Butyl 11-(((2S)-3-(4'(4-azidobutoxy)-2'-ethyl-[1,1'-biphenyl]-4-yl)-1-(((2S)-1-(((4(2-((2,4-bis(docosyloxy)benzyl)amino)-2-oxoethoxy)phenyl)(2,4dimethoxyphenyl) methyl)amino)-5-(3,5-dimethylphenyl)-1-oxopentan-2yl)amino)-1-oxopropan-2-yl)carbamoyl)-5-(CAN-1-(tertPetition 870260086043, of 08 / 24 / 2026, page 180 / 389 175 / 328 butoxy)ethyl)-8-(tert-butoxymethyl)-1-(9H-fluoren-9-yl)-3,6,9trioxo-2-oxa-4,7,10-triazatridecan-13-oate (N-Fmoc-Tag3-5AA) Tag3-4AA N-Fmoc-Tag3-5AA

[597] A solution of Tag3-4AA (230 mg, 106.83 pmol, 90% purity, 1 eq), AA5 (63.69 mg, 160.24 pmol, 1.5 eq) and HOAt (21.81 mg, 160.24 pmol, 22.42 pL, 1.5 eq) in DCM (4 mL) was added DIC (20.22 mg, 160.24 pmol, 24.81 pL, 1.5 eq) was added to a portion at 20°C under N2. The mixture was stirred at 20°C for 2 h. To monitor the reaction, a small amount of the residue was subjected to acid cleavage using a TFA cocktail (0.1 mL, TFA:TIPS:H2O:anisole = 95:2.5:2.5:4.5) for 1 h. LCMS showed that the reaction was completely converted. The mixture was triturated with ACN (20 mL*3) to generate the crude product N-Fmoc-Tag3-4AA (250 mg, 97.10 pmol, 90.90% yield, 90% purity) as a light yellow solid.

[598] LCMS (ESI): RT = 5.170 min, m / z calculated for C60H72N9O12, 1110.52, [M-Rink amide-Anchor-3tBu+5H]+; Rink amide=C17H18O4, anchor=C51H97NO2; m / z found 1110.4; LC-MS conditions: Method 7. Example 7. Synthesis (LPPS) of M2 in Tag4 7.1 Summary of Tag 4

[599] The synthetic route for the preparation of Tag4 is shown in Scheme 5 below. Scheme 5 Petition 870260086043, dated 08 / 24 / 2026, pp. 181 / 389 176 / 328

[600] Reagents and conditions: a) C22H4sBr (3.3 eq.), K2CO3 (8 eq.), DMF / THF, 90 °C, 12 h, 99.8%; b) L1AIH4 (3 eq.), THF, 700C, 3 h, 92.3%; c) PBr 3 (3 eq.), DCM, 20 °C, 3 h, 63%; d) 55A (1 eq.), K2CO3 (6 eq.), NMP, 90 °C, 16 h, 90.5%; e) NaBH4 (5 eq.), EtOH (1 V), THF (10 V), 70 °C, 12 h, 89.9%; f) I2 (1.8 eq.), LI2CO3 (0.02 eq.), TMSN3 (4.5 eq.), DCM, 12 h, 37°C, 80.9%; g) Pme3(3 eq.), H2O, THF / DCM, 20 ° C, 12 h, 66.8%. Total income: 25.5%

[601] Tris-alkylation of the 3,4,5-trihydroxybenzoyl ester with C22 alkyl bromide, followed by LAH reduction of the Tag4-1 ester yielded the Tag4-2 alcohol (Matsuda et al., Solution-Phase Synthesis of Oligodeoxyribonucleotides Using the H-Phosphonate Method with N-Unprotected 5'-Phosphite Monomers, RSC Adv. 11: 38094-38107 (2021), which is incorporated herein by reference in its entirety). Conversion of the Tag4-2 alcohol to the Tag4-3 bromine analog with triphenylphosphine and carbon tetrabromide, followed by alkylation to Tag4-3a, yielded the hex-alkylated derivative Tag44. The conversion of the ketone Tag4-4 to the alcohol Tag4-5 with sodium borohydride, followed by the conversion of the alcohol Tag4-5 to the azide Tag4-6 with trimethylsilylazide as a nucleophile in the presence of lithium carbonate as a base, with final reduction of the azide Tag4-6 with trimethylphosphine, yielded Tag4. Step a: Synthesis of methyl 3,4,5-tri(docosoxy)benzoate Petition 870260086043, dated 08 / 24 / 2026, pp. 182 / 389 177 / 328 (Tag4-1) I C22H45Br (3.3 eq.), K2CO3(8 eq.), ψ A / OH DMF / THF, 90 oC, 12 h, 99.8%u Il T ---------------------------------------► ί| ίΓC22H45 -V'Ah a “yU? θ / 0 θ22^45 Tag4-SM Tag4-1

[602] For a mixture of methyl 3,4,5-trihydroxybenzoate (5 g, 27.15 mmol, 1 eq.) and 1-bromodocosane (34.90 g, 89.60 mmol, 3.3 eq.) in DMF (100 mL) and THF (20 mL), K2CO3 (30.02 g, 217.22 mmol, 8 eq.) and the reaction mixture was stirred at 90 °C for 12 h. Most of the reagent was consumed and a new spot with lower polarity was formed on the TLC (PE / EtOAc = 3 / 1). After the reaction was complete, the reaction mixture was poured into purified water (1000 mL), the mixture was stirred for 1 hour, and the precipitated solid was collected by filtration. The resulting solid was ground with acetone (300 mL), the solid was collected by filtration, and the suspension was washed in methanol. After filtration, the resulting solid was dried under reduced pressure to yield the titrant compound as a whitish solid. The compound Tag41 (30.1 g, 27.12 mmol, 99.88% yield) was obtained as a gray solid. 1H NMR (400 MHz, chloroform-d) δ = 7.29 (s, 2H), 4.03 (dt, J = 2.5, 6.4 Hz, 6H), 3.91 (s, 2H), 3.93 - 3.87 (m, 1H), 1.85 - 1.71 (m, 6H), 1.54 - 1.45 (m, 6H), 1.28 (s, 108H), 0.90 (t, J = 6.8 Hz, 9H) ppm. Step b: Synthesis of [3,4,5-tri(Docosoxy)phenyl]methanol (Tag42) / θ θ22^45 ^22^45 Tag4-1 Tag4-2

[603] A solution of the compound Tag4-1 (1 g, 900.99 gmol, 1 Petition 870260086043, dated 08 / 24 / 2026, pp. 183 / 389 178 / 328 eq.) in THF (10 mL), L1AIH4 (102.59 mg, 2.70 mmol, 2.70 mL, 3.0 eq.) was added at 0°C. The mixture was then heated to 70°C for 3 h. TLC (PE / EA = 20 / 1) showed that most of the reagent was completely consumed and a new main spot was detected. The reaction mixture was extracted with 1 N HCl and stirred at 20°C for 1 h. The mixture was then filtered and the filter cake was concentrated to yield the product. The compound Tag4-2 (0.9 g, 831.88 pmol, 92.33% yield) was obtained as a gray solid. 1H NMR (400 MHz, chloroform-d) δ ppm 6.58 (s, 2 H) 4.62 (s, 2 H) 3.93 - 4.04 (m, 6 H) 1.72 - 1.87 (m, 6 H) 1.43 - 1.55 (m, 6 H) 1.28 (s, 108 H) 0.90 (t, J=6.79 Hz, 9 H). Step c: Synthesis of 5-(Bromomethyl)-1,2,3tri(docosoxy)benzene (Tag4-3) q^C22H45 Q--C22H45 / L JX PBr3(3 eq.), DCM, 20 °C, 3h, 63% X c22H45----ÍL-Lí----------------PY c22h45H0^AC Βγ^ΛΧ0 II C22H45θ22H45 Tag4-2 Tag4-3

[604] A solution of PBr3 (675.54 mg, 2.50 mmol, 3.0 eq.) in DCM (10 mL) was added to a solution of the compound Tag4-2 (0.9 g, 831.88 pmol, 1 eq.) in DCM (10 mL). The solution was then stirred at 20 °C for 3 h. TLC (PE / EA = 10 / 1) showed that the reagent was completely consumed, and a small polarity point was detected. The reaction mixture was extracted with H2O (50 mL) and ACN (50 mL) and the mixture was stirred at 20 °C for 1 h. It was then filtered and the filter cake was dried by evaporation of the solvent to give the product. The compound Tag43 (0.6 g, 524.12 pmol, 63.00% yield) was obtained as a white solid. 1H NMR (400 MHz, chloroform-d) δ ppm 6.58 (s, 2 H) 4.44 (s, 2 H) 3.92 - 4.00 (m, 6 H) 1.86 (dt, J=6.53, 3.26 Hz, H) 1.42 - 1.52 (m, 8 H) 1.26 (s, 125 H) 0.86 - 0.93 (m, 12 H). Step d: Synthesis of Bis[4-[[3,4,5tri(docosoxy)phenyl]methoxy]phenyl]methanone (Tag4-4) Petition 870260086043, dated 08 / 24 / 2026, pp. 184 / 389 179 / 328

[605] A solution of compound Tag4-3a (500 mg, 2.33 mmol, 1.0 eq.) and K2CO3 (1.94 g, 14.00 mmol, 6.0 eq.) in NMP (150 mL) was degassed and purged with N2 10 times for about 10 minutes. Then, the mixture was heated to 90 °C and then a solution of Tag4-3 (5.37 g, 4.69 mmol, 2.01 eq.) in NMP (350 mL) was added under N2. Then, the mixture was degassed and purged with N2 10 times for about 10 minutes, stirred at 90 °C for 16 hours. The TLC (PE / EA = 20 / 1) showed that the starting material was completely consumed and the desired point was detected. The reaction solution was slowly added to ACN (1000 mL) with stirring, then the reaction mixture was filtered; and the filter cake was washed with MeOH (250 mL x 3) and ACN (250 mL x 3). The filter cake was dried by evaporating the residual solvent to yield the product. The compound Tag4-4 (5.5 g, 2.11 mmol, 90.55% yield, 90% purity) was obtained as a white solid.1H NMR (400 MHz, chloroform-d) δ ppm 7.80 (d, J=8.75 Hz, 4 H) 6.99 - 7.09 (m, 4 H) 6.63 (s, 4 H) 5.03 (s, 4 H) 3.95 - 4.01 (m, 1.80 H) dd, J=14.07, 6.44 Hz, 12 H) 1.43 - 1.54 (m, 12 H) 1.26 (s, 226 H) 0.89 (t, J=6.69 Hz, 18 H). Step e: Synthesis of Bis[4-[[3,4,5tri(docosoxy)phenyl]methoxy]phenyl]methanol (Tag4-5) NaBH„ (5 eq.), EtOH (1 V), THF (10 V), 70 oC, 12 h, 89.9%

[606] A solution of Tag4-4 (5.5 g, 2.35 mmol, 1 eq.) in THF (100 mL) and EtOH (25 mL), slowly added NaBH4 Petition 870260086043, of 24 / 08 / 2026, p. 185 / 389 180 / 328 (444.21 mg, 11.74 mmol, 5.0 eq.), and the mixture was heated to 70 °C and stirred at 77 °C for 5 h. TLC (PE / EA = 10 / 1) showed that the starting material was completely consumed and a new spot was detected. The reaction mixture was slowly added to saturated NH4Cl / ACN (550 mL / 750 mL). The suspension was filtered and the resulting crystals were washed with ACN (250 mL x 3) and methanol (250 mL x 3) to yield the product. The compound Tag4-5 (5.5 g, 2.11 mmol, yield 89.92%, purity 90%) was obtained as a white solid. 1H NMR (400 MHz, chloroform-d) δ ppm 7.30 (d, J=8.63 Hz, 4 H) 6.96 (d, J=8.63 Hz, 4 H) 6.62 (s, 4 H) 5.81 (br s, 1 H) 4.94 (s, 4 H) 3.95 - 4.01 (m, 12 H) 1.74 - 1.84 (m, 12 H) 1.48 (br s, 12 H) 1.28 (s, 226 H) 0.90 (t, J=6.75 Hz, 18 H). Step f: Synthesis of 5-[[4-[Azido-[4-[[3,4,5tri(docosoxy)phenyl]methoxy]phenyl]methyl]phenoxy] methyl]-1,2,3tri(docosoxy)benzene (Tag4-6)

[607] To a mixture of compound Tag4-5 (5.5 g, 2.35 mmol, 1 eq.) and I2 (1.07 g, 4.22 mmol, 850.79 uL, 1.8 eq.) in DCM (105 mL) were added Li2CO3 (3.47 mg, 46.93 µmol, 31.67 uL, 0.02 eq.) and TMSN3 (1.22 g, 10.56 mmol, 1.39 mL, 4.5 eq.), then the reaction mixture was stirred at 37 °C for 12 h. The reagent was consumed, and the desired point was formed at TLC (PE / EtOAc = 20 / 1). The reaction solution was slowly added to ACN with stirring (750 mL) and saturated Na2SO3 (250 mL), then the reaction mixture was filtered; The filter cake was washed with methanol (250 mL*3) and ACN (250 mL*3). The filter cake was dried by evaporation of the residual solvent to generate the product. Tag4-6 (5.0 g, 1.90 mmol, yield of 80.95%, purity of 90%) was obtained as a white solid. 1H NMR (400 MHz, chloroform-d) δ ppm 7.23 (br d, J=8.63 Hz, 4H) 6.96 (br d, J=8.63 Hz, 4H) 6.61 (s, 4H) 5.62 (s, 1H) 5.65 (s, 1H) 4.93 (s, 4H) 3.94 - 3.99 (m, Petition 870260086043, dated 08 / 24 / 2026, pp. 186 / 389 181 / 328 12H) 1.76 - 1.84 (m, 12H) 1.43 - 1.50 (m, 12H) 1.27 (s, 226H) 0.87 - 0.90 (m, 18H). Step g: Synthesis of Bis[4-[[3,4,5tri(docosoxy)phenyl]methoxy]phenyl]methanamine (Tag4)

[608] To a solution of Tag4-6 (4.5 g, 1.90 mmol, 1 eq.) in THF (50 mL), DCM (50 mL) and H2O (2.5 mL), PMe3 (1 M, 5.70 mL, 3.0 eq.) was added. The reaction mixture was then stirred at 20 °C for 12 h. TLC (PE / EA = 20 / 1) showed that the reagent was completely consumed, and TLC (PE / EA = 1 / 1) showed that the desired point was detected. The reaction solution was slowly added to ACN (800 mL) and H2O (200 mL) with stirring. The reaction mixture was then filtered; the filter cake was ground again with ACN (800 mL) and then washed with MeOH (250 mL x 3) and ACN (250 mL x 3). The filter cake was dried by evaporation of the residual solvent, resulting in the product Tag4 (3.5 g, 1.27 mmol, yield 66.84%, purity 85%), obtained as a white solid. 1H NMR (400 MHz, chloroform-d) δ ppm 7.28 7.33 (m, 4H) 6.90 - 6.99 (m, 4H) 6.60 - 6.66 (m, 4H) 5.16(s, 1H) 4.93 (s, 4H) 3.95 - 4.01 (m, 12H) 1.76 - 1.82 (m, 12H)1.48 (br s, 12H) 1.28 (s, 226H) 0.88 - 0.92 (m,18H). 7.2 Synthesis of Tag4-M2

[609] Figure 5 and Table 8 below describe the synthesis of M2 using Tag4. Table 8. Step # Fmoc coupling Product # amino acid DIC HOAt Yield # 20% piperidine in THF Yield # MS (M+H) + 1 a AA1 1.5 eq. 1.5 eq. 1.5 eq. 70.4% b 20 V 100.0% Tag4 -1AA Petition 870260086043, dated 08 / 24 / 2026, pp. 187 / 389 182 / 328 2 c AA2 1,5 eq. 1,5 eq. 1,5 eq. 67,6% d 20 V 96,3% Tag4 -2AA 585,40 [M- Tag4+H] + 3 e AA3 1,5 eq. 1,5 eq. 1,5 eq. 59,1% f 20 V 84,6% Tag4 -3AA 700,50 [M-tBu- Tag4+H] + 4 g AA4 1,5 eq. 1,5 eq. 1,5 eq. 86,4% h 20 V 99,2% Tag4 -4AA 787,50 [M-tBu- Tag4+H] + 5 i AA5 1,5 eq. 1,5 eq. 1,5 eq. 85,7% j 20 V 82,0% Tag4 -5AA 888,50 [M- 3tBu- Tag4+4H ] + 6 k AA6 1,5 eq. 1,5 eq. 1,5 eq. 71,5% l 20 V 93,0% Tag4 -6AA 1067,60 [M- 3tBu- Tag4+4H + ] 7 m AA7 5 eq. 5 eq. 5 eq. 90,4% n 20 V 87,8% Tag4 -7AA 1168,60 [M- 3tBu- Tag4+4H + ] 8 o AA8 1,5 eq. 1,5 eq. 1,5 eq. 86,8% p 20 V 94,2% Tag4 -8AA 1225,70 [M- 3tBu- Tag4+4H + ] 9 q DMB- AA9 1,5 eq. 1,5 eq. 1,5 eq. 88,1% r 20 V 100,0% Tag4 -9AA 683,20 [M- 4tBu- DMB- Tag4+7H ]2+ 10 s AA10 1,5 eq. 1,5 eq. 1,5 eq. 90,0% Tag4 10AA 787,00 [M- 4tBu- DMB- Trt- Tag4+8H ]2+ 11 t clivagem 0,7%* M2 786,2 [M+H] + *: o baixo rendimento é devido à clivagem não eficiente de Petição 870260086043, de 24 / 08 / 2026, pág. 188 / 389 183 / 328 Tag4 M2. General procedure F for amide coupling to prepare N-Fmoc-Tag4-nAA

[610] To a solution of Tag4 or Tag4-(n-1)AA (1 eq.) and AAn (1.5 eq.) and HOAt (1.5 eq.) in DCM (20 V), DIC (1.5 eq.) and HOAt (1.5 eq.) were added. The solution was stirred at 20 °C for 12 h. A small sample was collected and subjected to acid cleavage using a TFA cocktail (TFA:TIPS:H2O = 95:2.5:2.5). The sample was filtered and analyzed by LCMS, which showed that the reagent was consumed and the desired mass was detected. ACN (80 V) was added to the reaction solution and the resulting suspension was filtered and washed with ACN (20 V x 2) to obtain a whitish solid. The solvent was removed by filtration and the filter cake was dried by evaporation of the residual solvent to obtain the N-Fmoc-Tag4-nAA product as a whitish solid, which was used directly in the next step. General procedure G for Fmoc deprotection to generate Tag4-nAA

[611] A solution of the compound N-Fmoc-Tag4-nAA (1 eq.) in 20% piperidine in THF and DCM (20 V) was stirred at 20 °C for 2 h. TLC (PE / EA = 1 / 1) showed that the reagent was completely consumed and the desired point was detected. ACN (200 V) was added to the reaction solution and the resulting suspension was filtered and washed with ACN (40 V x 2) to obtain Tag4-nAA as a whitish solid. The crude product was dried under reduced pressure and used directly in the next step without further purification. Step 1: Synthesis of (2S)-2-Amino-N-[bis[4-[[3,4,5tri(docosoxy)phenyl]methoxy]phenyl]methyl]-5-(3,5dimethylphenyl)pentanamide (Tag4-1AA) Petition 870260086043, dated 08 / 24 / 2026, pp. 189 / 389 184 / 328 Tag4 Tag4-1AA

[612] The reaction was carried out following general procedure F for amide coupling using Tag4 (2.5 g, 1.07 mmol, 1 eq.) and AA1 (709.88 mg, 1.60 mmol, 1.5 eq.). N-Fmoc-Tag4-1AA (2.6 g, 751.31 pmol, 70.41% yield, 80% purity) was obtained as a whitish solid. LC-MS: RT = 4.061 min, calculated mass 443.23, m / z found 443.20 [Anchor+H]+; (anchor = Ci59H2860s, MS = 2325.21). LC-MS condition: Method 12. anchor = Tag4.

[613] The reaction was carried out following the general procedure G for deprotection of Fmoc using N-Elnoc-Tag4-1AA (2.0 g, 722.41 umol, 1 eq.). Tag4-1AA (1.6 g, crude) was obtained as a white solid which was used directly in the next step. LC-MS: 443.2 (M+H) + . Step 2: Synthesis of (2R)-2-[[(2S)-2-Amino-3-[4-[4-(4azidobutoxy)-2-ethyl-phenyl]phenyl]propanoyl] amino]-N-[bis[4[[3,4,5-tri(docosoxy)phenyl]methoxy]phenyl]methyl]-5-(3,5dimethylphenyl) pentanamide (Tag4-2AA) Tag4-1AA 2) AA2; de-Fmoc Tag4-2AA

[614] The reaction was carried out following general procedure F for amide coupling using Tag4-1AA (1.6 g, 628.37 pmol, 1 eq.), N-Einoc-Tag4-2AA (1.9 g, 424.52 pmol, 67.56% of Petition 870260086043, dated 08 / 24 / 2026, pp. 190 / 389 185 / 328 yield, 70% purity) was obtained as a white solid that was used directly in the next step. LC-MS: RT = 5.525 min, calculated mass for C49H55NeO5+807.42, m / z found 807.40 [Anchor +H]+; (anchor = CisgibseOs, MS = 2325.21). LCMS condition: Method 12. (anchor = Tag4).

[615] The reaction was carried out following the general procedure G for deprotection of Fmoc using N-Einoc-Tag4-2AA (1.9 g, 606.46 pmol, 1 eq.). Tag4-2AA (1.7 g, 584.05 pmol, 96.31% yield) was obtained as a whitish solid. LC-MS: RT = 3.534 min, calculated mass for C47H55NeO5+783.42, m / z found 783.40 [M-anchor + C13H11O2+H]+; (anchor = C159H286O8, MS = 2325.21); calculated mass for C34H45NeO3+585.35, m / z found 585.40 [M-anchor+H]+; (anchor=Ci59H28608, MS=2325, 21); LCMS Condition: Method 12. (anchor = Tag4) Step 3: Synthesis of tert-Butyl(3S)-3-Amino-4-[[(IS)-1-[[4[4-(4-azidobutoxy)-2-ethyl-phenyl] phenyl]methyl]-2-[[(IS)—1[bis[4-[[3,4,5tri(docosoxy)phenyl]methoxy]phenyl]methylcarbamoyl]-4-(3,5dimethylphenyl)butyl]amino]-2-oxo-ethyl]amino]-4-oxo-butanoate (Tag4-3AA) Tag4-2AA

[616] The reaction was carried out following general procedure F for amide coupling using Tag4-2AA (1.7 g, 584.05 pmol, 1 eq.). N-Fmoc-Tag4-3AA (1.9 g, 345.02 pmol, 59.07% yield, 60% purity) was obtained as a whitish solid. LC-MS: RT = 5.159 min, mass calculated for CssHeoNvOs4 922.41, m / z found 922.40 [M-anchor +H]+; (anchor = C159H286O8, MS = 2325.21). LC-MS condition: Method 12. (anchor = Tag4)

[617] The reaction was carried out following the general procedure G Petition 870260086043, dated 08 / 24 / 2026, pp. 191 / 389 186 / 328 for deprotection of Fmoc using N-Fmc-Tag4-3AA (1.9 g, 575.04 pmol, 1 eq.), Tag4-3AA (1.50 g, 486.71 pmol, yield of 84.64%) was obtained as a whitish solid. LC-MS: RT = 3.633 min, mass calculated for CsiHeoNvOs 4898.44, m / z found 898.50 [M-tBu-anchor + C13H11O2 + H]+; (anchor = CisgíRseOs, MS = 2325.21); mass calculated for CasHsoNvOe 4700.37, m / z found 700.50 [MtBu-anchor + H]+; (anchor=Ci59H2860s, MS=2325, 21); LCMS Condition: Method 12. (anchor = Tag4) Step 4: Synthesis of tert-Butyl(3S)-3-[[[(2S)-2-Amino-3-tertbutoxy-propanoyl]amino]-4-[[(IS)-1-[[4-[4-(4-azidobutoxy) -2ethyl-phenyl]phenyl]methyl]-2-[[(IS)-1-[bis[4-[[3,4,5tri(docosoxy)phenyl]methoxy]phenyl]methylcarbamoyl]-4-(3,5dimethylphenyl)butyl]amino]-2-oxo-ethyl]amino]-4-oxo-butanoate (Tag4-4AA)

[618] The reaction was carried out following general procedure F for amide coupling using Tag4-3AA (1.5 g, 486.71 pmol, 1 eq.) in DCM (50 mL). N-Elnoc-Tag4-4AA (1.45 g, 420.62 pmol, yield 86.42%) was obtained as a whitish solid. LC-MS: RT = 5.019 min, mass calculated for CseHesNgOict 1009.40, m / z found 1009.40 [M-anchor+H]+; (anchor = C159H286O8, MS = 2325.21). LCMS condition: Method 12. (anchor = Tag4).

[619] The reaction was carried out following the general procedure G for deprotection of Fmoc using N-Einoc-Tag4-4AA (1.4 g, 406.11 pmol, 1 eq.). Tag4-4AA (1.30 g, 403.09 pmol, 99.26% yield) was obtained as a whitish solid. LC-MS: RT = 3.527 min, calculated mass for: CsiHesNsOict 985.47, m / z found 985.50 [M-tBu-anchor+H]+; (anchor = C159H286O8, MS = 2325.21); calculated mass for CoHssNeOs 4787.41, m / z found Petition 870260086043, dated 08 / 24 / 2026, pp. 192 / 389 187 / 328 787.50 [M-tBu-anchor +H] +; (anchor = C159H286O8, MS = 2325, 21); LCMS Condition: Method 12. (anchor = Tag4) Step 5: Synthesis of tert-Butyl (3S)-3-[[[(2S)-2-[[(2S,3R)-2Amino-3-tert-butoxy-butanoyl]amino]-3-tert-butoxypropanoyl]amino]-4-[[(lS)-1-[[4 —[4 —(4-azidobutoxy)-2-ethylphenyl]phenyl]methyl]-2-[[(IS)-1-[bis[4-[[3,4,5tri(docosoxy)phenyl]methoxy]phenyl]methylcarbamoyl]-4-(3,5dimethylphenyl)butyl]amino]-2-oxo-ethyl]amino]-4-oxo-butanoate (Tag4-5AA)

[620] The reaction was carried out following the general procedure F for amide coupling using Tag4-4AA (1.45 g, 420.62 pmol). N-Fmoc-Tag4-5AA (1.3 g, 360.66 pmol, yield of 85.74%) was obtained as a whitish solid. LC-MS: RT=4.894 min, calculated mass for CeoHggNgOig + 1110.52, m / z found 1110.60 [MtBu-anchor +H]+; (anchor=Ci59H2860s, MS=2325.21); calculated mass for CgaHsgNgOi® 1308.57, m / z found 1308.60 [M-tBu-anchor+H]+; (anchor=Ci59H2860s, MS=2325, 21); LCMS Condition: Method 12. (anchor = Tag4)

[621] The reaction was carried out following the general procedure G for deprotection of Fmoc using N-Einoc-Tag4-5AA (1.30 g, 360.66 pmol, 1 eq.). Tag4-5AA (1.0 g, 295.66 pmol, yield of 81.98%) was obtained as a whitish solid which was used directly in the next step. LC-MS: RT = 3.557 min, mass calculated for: CssHggNgOig* 1086.52, m / z found 1086.30 [M-3 tBu-anchor + [C13H11O2+4H] +; (anchor = CisgHgseOs, MS = 2325.21); calculated mass for CgsHegNgOict 888.45, m / z found 888.50 [M-3tBuâncora+4H]+; (anchor=Ci5gH28608, MS=2325.21); LCMS condition: Method 12. (anchor = Tag4) Petition 870260086043, dated 08 / 24 / 2026, pp. 193 / 389 188 / 328 Step 6: Synthesis of tert-Butyl (3S)-3-[ [ (2S)-2-[ [ (2S,3R)-2[[2-Amino-3-(2-fluorophenyl)-2-methyl-propanoyl]amino]-3-tertbutoxy-butanoyl]amino]-3-tert-butoxy-propanoyl]a mino]-4[[(IS)—1-[[4-[4-(4-azidobutoxy)-2-ethyl-phenyl]phenyl]methyl]-2[[(lS)-1-[bis[4-[[3,4,5-tri(docosoxy)phenyl]methoxy] phenyl]methylcarbamoyl]-4-(3,5-dimethylphenyl)butyl]amino]-2-oxoethyl]amino]-4-oxo-butanoate (Tag4-6AA)

[622] The reaction was carried out following general procedure F for amide coupling using Tag4-5AA (1.0 g, 295.66 pmol, 1 eq.). N-Finoc-Tag4-6AA (0.8 g, 211.43 pmol, yield 71.51%) was obtained as a whitish solid. LC-MS: RT = 5.208 min, mass calculated for C7oHs2FNioOi3+1289.60, m / z found 1289.60 [M-3tBu-anchor+4H]+; (anchor = C159H286O8, MS = 2325.21); LCMS condition: Method 12. (anchor = Tag4)

[623] The reaction was carried out following the general procedure G for deprotection of Fmoc using N-Fmoc-Tag4-6AA (0.8 g, 211.43 pmol, 1 eq.). Tag4-6AA (0.7 g, 196.55 pmol, yield 92.96%) was obtained as a whitish solid. LC-MS: RT = 3.697 min, mass calculated for CesHsgFNioOis41265.60, m / z found 1265.70 [M-3tBu-anchor+Ci3HuO2+4H]+, (anchor = C159H286O8, MS = 2325.21); RT = 3,630 min, mass calculated for C55H72FNioOh+1067.53, m / z found 1067.60 [M-3tBu-anchor+4H]+; (anchor=Ci59H28608, MS=2325,21); LCMS Condition: Method 12. (anchor = Tag4) Step 7: Synthesis of tert-Butyl (3S)-3-[[(2S)-2-[[(2S,3R)-2[ [2-[[(2S,3R)-2-Amino-3-tert-butoxy-butanoyl]amino]-3-(2fluorophenyl)-2-methyl-propanoyl]amino]-3-tert-butoxybutanoyl ]amino]-3-tert-butoxy-propanoyl]amino]-4-[[(IS)-1-[[4[4-(4-azidobutoxy)-2-ethyl-phenyl]phenyl]methyl]-2-[[(lS)-lPetition 870260086043, of 08 / 24 / 2026, p. 194 / 389 189 / 328 [bis[4-[[3,4,5tri(docosoxy)phenyl]methoxy]phenyl]methylcarbamoyl]-4-(3,5dimethylphenyl)butyl]amino]-2-oxo-ethyl]amino]-4-oxo-butanoate (Tag4-7AA) Tag4-6AA Tag4-7AA

[624] The reaction was carried out following general procedure F for amide coupling using Tag4-6AA (0.7 g, 196.55 pmol, 1 eq.). N-Fmoc-Tag4-7AA (0.7 g, 177.62 pmol, 90.37% yield) was obtained as a whitish solid. LC-MS: RT = 5.224 min, calculated mass for C74H8gFNuOi5+1390.64, m / z found 1390.60 [M-3tBu-anchor+4H]+; (anchor = CisgibseOs, MS = 2325.21); LC-MS condition: Method 12. (anchor = Tag4)

[625] The reaction was carried out following the general procedure G for deprotection of Fmoc using N-Fmoc-Tag4-1AA. (0.7 g, 177.62 pmol, 1 eq.) . Tag4-7AA (0.58 g, 155.97 pmol, yield 87.81%) was obtained as a whitish solid which was used directly in the next step. LC-MS: RT = 3.869 min, mass calculated for CvzHsgFNuOis41366.65, m / z found 1366.70 [M3tBu-anchor+Ci3HuO2+4H]+, (anchor = CisgibseOs, MS = 2325.21); calculated mass for CsgHggFNuOia41168.58, m / z found 1168.60 [M3tBu-anchor+4H]+; (anchor=Ci5gH28608, MS=2325.21); LCMS condition: Method 12. (anchor = Tag4) Step 8: Tert-Butyl Synthesis (3S)-3-[[(2S)-2-[[(2S,3R)-2[[2-[[(2S,3R)-2-[(2-Aminoacetyl)amino]-3-tert-butoxybutanoyl]amino]-3-(2-fluorophenyl)-2-methyl-prop anoyl]amino]-3tert-butoxy-butanoyl]amino]-3-tert-butoxy-propanoyl]amino]-4[[(IS)—1-[[4-[4-(4-azidobutoxy)-2-ethyl-phenyl]phenyl] methyl]-2 [[(IS)-1-[bis[4-[[3,4,5tri(docosoxy)phenyl]methoxy]phenyl]methylcarbamoyl]-4-(3,5 Petition 870260086043, dated 08 / 24 / 2026, pp. 195 / 389 190 / 328 dimethylphenyl)butyl]amino]-2-oxo-ethyl]amino]-4-oxo-butanoate (Tag4-8AA) Tag4-7AA Tag4-8AA

[626] The reaction was carried out following general procedure F for amide coupling using Tag4-7AA (0.6 g, 161.35 pmol, 1 eq.). N-Finoc-Tag4-8AA (0.56 g, 140.07 pmol, yield 86.81%) was obtained as a whitish solid. LC-MS: RT = 5.092 min, mass calculated for CgeHggFNigOie* 1447.67, [M-3tBuâncora+4H]+; (âncora = CisgHgseOg, MS = 2325.21); LCMS condition: Method 12. (âncora = Tag4)

[627] The reaction was carried out following the general procedure G for deprotection of Fmoc using N-Fmoc-Tag4-8AA (0.56 g, 140.07 pmol, 1 eq.). Tag4-8AA (0.5 g, 132.42 pmol) was obtained as a whitish solid which was used directly in the next step. LC-MS: RT = 3.848 min, calculated mass for C11HggFNigO11A 1225.60, m / z found 1225.70 [M-3tBu-anchor+4H]+, (anchor = C11HggSEO1, MS = 2325.21); calculated mass for C11HggFNigO11A 1423.67, m / z found 1423.70 [M-3tBu-anchor+C13HuO2+4H]+; (anchor = CisgHgseOg, MS = 2325, 21); LCMS Condition: Method 12. (anchor = Tag4) Step 9: Synthesis of tert-Butyl (3S)-3-[[(2S)-2-[[(2S,3R)-2[ [2- [ [ (2S,3R) -2- [ [2- [ [ (2S) -2-Amino-3-[ 1-[ (2,4-dimethoxyphenyl)methyl]tetrazol-5yl]propanoyl]amino]acetyl]amino]-3-tert-butoxybutanoyl]amino] -3-(2-fluorophenyl)-2-methylpropanoyl]amino]-3-tert-butoxybutanoyl ]amino]-3-tert-butoxypropanoyl]amino]-4-[[(IS)-1-[[4[4-(4-azidobutoxy)-2-ethylphenyl]phenyl]methyl]-2-[[(lS)-l[bis[4-[[3,4,5tri(docosoxy)phenyl]methoxy]phenyl]methylcarbamoyl]-4-(3,5dimethylphenyl)butyl]amino]-2-oxoethyl]amino]-4-oxobutanoate Petition 870260086043, de 24 / 08 / 2026, p. 196 / 389 191 / 328 (Member4-9AA) Tag4-£AA Tag4-9AA

[628] The reaction was carried out following the general procedure F for amide coupling using Tag4-8AA (105.19 mg, 198.64 pmol, 1.5 eq.), DMB-AA9 (105.19 mg, 198.64 pmol, 1.5 eq.), DIC (25.07 mg, 198.64 pmol, 30.76 pL, 1.5 eq.) and HOAt (27.04 mg, 198.64 pmol, 27.79 pL, 1.5 eq.). N-Fmoc-Tag4-9AA (0.5 g, 116.62 pmol, 88.07% yield) was obtained as a whitish solid. LC-MS: RT=4.817 min, mass calculated for CsoHgsFNivOi?4793, 86., found 794.30 [M-3tBu-PMB-anchor+7H]2+; (anchor=Ci59H28608, MS=2325.21); calculated mass for C95H106FN17O19 892.89, found 893.50 [M-3tBu-PMB-anchor+7H]+; (anchor=Ci5gH28608, MS=2325.21); LCMS condition: Method 12. (anchor = Tag4)

[629] The reaction was carried out following the general procedure G for deprotection of Fmoc using N-Einoc-Tag4-9AA (0.5 g, 116.62 pmol, 1 eq). Tag4-9AA (0.5 g, crude) was obtained as a whitish solid. LC-MS: RT = 3.838 min, mass calculated for CegHseFNigOie4683.80, m / z found 683.20 [M-4tBu-DMBâncora+7H]2+, (anchor = CisgHgseOs, MS = 2325.21); mass calculated for CggHgeFNigOis22782.85, m / z found 782.30 [M-4tBu-DMBâncora+7H]+; (anchor=Ci5gH28608, MS=2325.21); LCMS Condition: Method 12. (anchor = Tag4) Step 10: Tert-Butyl Synthesis (3S)-4-[[[(IS)-1-[[4-[4-(4Azidobutoxy)-2-ethyl-phenyl]phenyl]methyl]-2-[[(lS)-1-[bis[4[[3,4,5-tri(docosoxy)phenyl]methoxy]phenyl]methylcarbamoyl]-4(3,5-dimethylphenyl) butyl]amino]-2-oxo-ethyl]amino]-3-[[(2S)-3tert-butoxy-2-[[(2S,3R)-3-tert-butoxy-2-[[2-[[(2S,3R)-3-tertbutoxy-2 -[[2-[[(2S)-3-[1-[(2,4-dimethoxyphenyl)methyl]tetrazol-5yl]-2-[[2,2-dimethyl-3-oxo-3-[2-(3-tritylimidazol-4-Petition 870260086043, dated 08 / 24 / 2026, page. 192 / 328 yl)ethylamino]propanoyl]amino]propanoyl]amino]acetyl]amino]butanoyl]amino]-3-(2-fluorophenyl)-2-methylpropanoyl]amino]butanoyl]amino]propanoyl]amino]-4-oxobutanoate (Tag4-10AA) Tag4-9AA Tag4-WAA

[630] The reaction was carried out following general procedure F for amide coupling using Tag4-9AA (0.5 g, 123.00 pmol, 1 eq.) in DCM (15 mL) and THF (15 mL), AA10 (86.26 mg, 184.50 pmol, 1.5 eq.), DIC (23.28 mg, 184.50 pmol, 28.57 pL, 1.5 eq.) and HOAt (25.11 mg, 184.50 pmol, 25.81 pL, 1.5 eq.). Tag4-10AA (0.5 g, 110.75 pmol, 90.04% yield) was obtained as a whitish solid which was used directly in the next step. LCMS: RT= 3,874 min, mass calculated for C7sHioiFN2oOi72+786,37, found 787,00 [M-4tBu-DMB-Trt-anchor+8H]2+; (anchor=Ci59H28608, MS=2325.21); calculated mass for C88H111FN20O19 885.41, found 886.00 [M-4tBu-DMB-Trt-anchor+8H]+; (anchor=Ci59H28608, MS=2325.21); LCMS condition: Method 12. Note: (anchor = Tag4) Step 11: Synthesis of Bis[4-[[3,4,5tri(docosoxy)phenyl]methoxy]phenyl]methanamine (M2)

[631] To a mixture of Tag4-10AA (432.77 mg, 95.86 pmol, 1 eq.) in TFA (4.5 mL) and H2O (0.25 mL) was added triisopropylsilane (143.92 mg, 908.82 pmol, 186.67 pL, 9.48 eq.) in a portion at 20 °C under N2. The mixture was stirred at 20 °C for 1.5 h. LC-MS showed that the desired mass was detected. LC-MS: RT = 3.822 min, m / z calculated for C75H100FN20O17, 1570.75 [M-Boc Petition 870260086043, dated 08 / 24 / 2026, pp. 198 / 389 193 / 328 4tBu+2H]2+, m / z found 786.20, LCMS condition: Method 12. The mixture was filtered and the filtrate was diluted with t-BuOMe (1000 mL) to give a precipitate, which was centrifuged for 10 min (5000 R) to give the crude product. The residue was purified by prepHPLC (column: Welch Xtimate C18 100*40mm*3um; mobile phase: [water (TFA)-ACN]; B%: 30%-60%, 15 min). Compound M2 (1 mg, 5.98 e-1 µmol, 94% purity) was obtained as a white solid. LCMS (ESI): RT = 3.748 min, m / z calculated for C75H100FN20O17 1570.75 [M-Boc-4tBu+2H]2+, m / z found 786.20, LCMS condition: Method 12. HPLC RT = 9.411 min, 94% purity. Example 8. Synthesis (LPPS) of M1 and M3 in Tag5 8.1 Summary of Tag 5

[632] Tag5 was prepared in 10 steps, as shown in Scheme 6 below. Scheme 6 Tag5-1 Tag5-2 Tag5-3 Tag5-4 Tag5-8 Tag5-9 Tag5

[633] Tag5-3 was prepared from methyl 3,4,5-trihydroxybenzoate as described in Horenstein et al., Synthesis of Unprotected (±)-Tunichrome An-1, a Tunicate Blood Pigment, J. Am. Chern. See. 111(16):6242-6246 (1989), which is here Petition 870260086043, dated 08 / 24 / 2026, pp. 199 / 389 194 / 328 incorporated by reference in its entirety. Reductive amination of Tag5-3a with 2 eq. of Tag5-3 gave Tag5-4 in a 70% yield. Removal of the N-allyl group from Tag5-4 with 1,3-dimethylbarbituric acid in the presence of Pd(PPh3)4 catalyst yielded Tag5-5, which was coupled with Tag5-5a to form Tag5-6. Deprotection of Fmoc from Tag5-6 with piperidine yielded Tag5-7. Protection of N-alloc from Tag5-7 and subsequent removal of TBS in Tag5-8 and alkylation with C22 alkyl bromide in a single vessel yielded Tag5-9. Removal of the N-alloc group from Tag5-9 yielded the final product, Tag5. Substitution of N-Fmoc from Tag55a with N-alloc was experimented with for further improvement; However, Tag5-5a without N-Fmoc was poorly soluble in organic solvents. The amounts and yields for each step are summarized in Table 9 below. Petition 870260086043, dated 08 / 24 / 2026, pp. 200 / 389 195 / 328 Table 9. Quantities and Yields for Intermediaries and Tag5 Structure MF MW Quantity Age (kg) Purity at LC Yield Physical Property IUPAC Name Purification MP o C OTBDMS TBDMSO: TBDMSO °\ C26H50O5SÍ3 526.9 7.9 99% 90% Trituration; white solid 70.72 methyl 3,4,5-tris((tert-butyldimethylsilyl)oxy)benzoate OTBDMS TBDMSO^A. JL^A^oh TBDMSO C25H50O4SÍ3 498.9 3.48 99% 90% Crude Whitish solid 69.70 (3,4,5-tris((tert-butyldimethylsilyl)oxy)phenyl)methanol OTBDMS TBDMSO^X TBDMSO C25H48O4SÍ3 496.9 3.13 99% 90% Crude Yellow solid 73.33 3,4,5-tris((tert-butyldimethylsilyl)oxy)benzaldehyde OTBDMS TBDMSO. ' Λ.ΓΒΡ,.,β jl OTBDMS Â / L / OTBDMS TBDMSO tris((tertbutyldimethylsilyl)oxy) benzyl)prop-2-en-1amine 2 2 OQ »ees oot Oot '5 O o (0 (0 2 2 QQ m tn HH C50H99NO6SI6 978.8 1.69 95% 92% Yellow trituration oil bis(3,4,5-tris((tertbutyldimethylsilyl)oxy) benzyl)amine o rj^U OTBDMS .OTBDMS T° ΓΤ Fmoc-.^A., / :·..,, ^''^'OTBDMS : °ΎA TBDMSO'^^'OTBDMS OTBDMS C82H126N2O12SÍ6 1500.4 2.2 85% 83% Yellow crude oil (9H-fluoren-9-yl)methyl ((4- (2-(bis(3,4,5tris((tert-butyldimethylsilyl)oxy)benzyl)amino)-2oxoethoxy)phenyl)(2,4-. Petition 870260086043, dated 08 / 24 / 2026, pp. 201 / 389 196 / 328 dimethoxyphenyl)methyl)carbamate 0 OTBDMS JyiTBDMS r^^^OTBDMS °£1 TBDMSO'^Y^OTBDMS OTBDMS C67H116N2O10SI6 1278.2 1.8 84% 94% Yellow crude oil 2-(4-(amino(2,4-dimethoxyphenyl)methyl)phenoxy)-N,N-bis(3,4,5-tris((tert-butyldimethylsilyl)oxy)benzyl)acetamide O r<\ OTBDMS X.OTBDMS d>^ / A'OTBDMS O^O / °A TBDMSO'^^^Y^'OIBDMS OTBDMS C71H120N2O12SI6 1362.2 1.6 98% 95% Column purification Light yellow allyl gum ((4-(2- (bis(3,4,5-tris((tert-butyldimethylsilyl)oxy)benzyl)amino)-2oxoethoxy)phenyl)(2,4-dimethoxyphenyl)methyl)carbamate “Hr1 O °' 8 O 0-0 OZ “z “z 4 SSB C167H300N2O12 2528.2 0.40 95% 80% Column purification Whitish solid 74.28 allyl ((4-(2- (bis(3,4,5tris(docosyloxy)benzyl)amino)-2oxoethoxy)phenyl)(2,4-dimethoxyphenyl)methyl)carbamate Petition 870260086043, dated 08 / 24 / 2026, p. 202 / 389 197 / 328 0 0 A 0'^“ -Λα ΛΛ 0^45 C22H45^ox^ / AQaC22H45 0_ U Ο22Μ45 C163H296N2O10 2444.2 0.37 95% 95 Trituration Off-white solid 75.9 2-(4-(amino(2,4- dimethoxyphenyl)methyl)phenoxy)-N,N-bis(3,4,5tris(docosyloxy)benzyl)acetamide Petition 870260086043, dated 08 / 24 / 2026, pp. 203 / 389 198 / 328 Step a: Synthesis of methyl 3,4,5-Tris((tert-butyldimethylsilyl)oxy)benzoate (Tag5-1) Tag5-SM Tag5-1

[634] To a clear solution of methyl 3,4,5-trihydroxybenzoate (3 kg, 16.29 mol, 1 eq) in DMF (24 L), imidazole (4.99 kg, 73.31 mol, 4.5 eq) was added in one portion to give a clear solution. TBDMSCl (8.59 kg, 57.02 mol, 6.99 L, 3.5 eq) was added in four portions (2.148 kg x 4) over a period of 2 hours at a rate sufficient to maintain the internal temperature between 25°C and 30°C under N2. After the addition, a yellow solution was obtained. The reaction was stirred at 25°C for 16 h under N2 until a thick suspension was formed. TLC results indicated that the starting material was completely consumed and a new main point (petroleum ether:EtOAc = 9:1, R f = 0.58) was detected. The reaction mixture was pumped into transit barrels (2 x 20 L).A saturated solution of NaHCO3 (15 L) was loaded into a 50 L jacketed flask. 20 L (1 / 2 volume) of the reaction suspension were added to the saturated NaHCO3 solution (15 L) above with intensive stirring and extracted with PE (6 L x 2). The other (1 / 2 volume) of the reaction mixture was treated as above. All organic layers were combined, washed with brine (10 L) and dried over Na2SO4. The organic layer was filtered and concentrated under reduced pressure (~45°C, -0.8 atm) to give ~10 kg of light green oil. The light green oil was dissolved in MeOH (28 L) and stirred at 0~4°C (internal temperature) for 12 h. The white solid precipitated. The product Tag5-1 (7.8 kg, 14.80 mol, yield of...) 90.86%) was obtained as a white solid by filtration and dried under reduced pressure. 1HNMR: (400 MHz, CDCl3) δ = 7.23 (s, 2H), 3.85 (s, 3H), 1.00 (s, 9H), 0.99 - 0.86 (m, 18H), 0.24 (s, 12H), 0.15 (s, 6H); LC-MS: (analyzed by Method 1) Rt = 3.183 min, Petition 870260086043, of 24 / 08 / 2026, p. 204 / 389 199 / 328 m / z = 527.3 [M+H]+. Step b: Synthesis of [3,4,5-Tris[[tercbutyl(dimethyl)silyl]oxy]phenyl]methanol (Tag5-2) LiAIH4(0.75 eq) THF (8 V) at 77 °C, 3 h

[635] A solution of Tag5-1 (4 kg, 7.59 mol eq) in THF (15 L) was added to a suspension of LAH (216.09 g, 5.69 mol, 0.75 eq) in THF (16 L) at a rate sufficient to maintain a gentle reflux (internal temperature: 66 °C). The reaction mixture was stirred at an internal temperature of 66 °C (oil bath temperature: 77 °C) for 3 h. TLC indicated that Tag5-1 was completely consumed and a new spot (petroleum ether:ethyl acetate = 10:1, Rf = 0.41) was formed. The reaction mixture was cooled to (internal temperature: 0 °C) and diluted with 12 L of methyl-1-butyl ether (MTBE). The reaction mixture was stirred rapidly, and 216 mL of water were added dropwise until the color changed from gray to white. Then, 216 mL of NaOH solution (15% by weight) were added. The resulting mixture was stirred for 10 minutes. Water (620 mL) and silica gel (500 g) were added sequentially to the reaction mixture. The heterogeneous mixture was filtered through Celite and the resulting filtrate was concentrated under vacuum to obtain a colorless oil. Subsequently, it was pumped out by an oil pump to remove the solvent residue and obtain Tag5-2 (3.48 kg, 6.84 mol, 90.1% yield, 98% purity) as a white solid. 1H NMR (400 MHz, CDCl3) δ = 6.50 (s, 2H), 4.49 (s, 2H), 1.49 (br s, 1H), 1.00 (s, 9H), 0.95 (s, 18H), 0.21 (s, 12H), 0.13 (s, 6H); LC-MS: (analyzed by method 1) Rt= 3.25 min, m / z=481.3 [M+H-H2O]+. Step c: Synthesis of 3,4,5-Tris[[tertbutyl(dimethyl)silyl]oxy]benzaldehyde (Tag5-3) Petition 870260086043, dated 08 / 24 / 2026, pp. 205 / 389 200 / 328 OTBDMS OTBDMS TBDMSO. XPCC(11 ec<) TBDMSO. THE M -----~ Y1 JL Xx ^OH DCM (8 V) Λ X. AD TBDMSO 20 °C 20 h TBDMSO Tag5-2 Tag5-3

[636] A solution of Tag5-2 (3.48 kg, 6.98 mol, 1 eq) in DCM (16 L) at 0 °C was added to a suspension of PCC (1.58 kg, 7.32 mol, 1.05 eq) in DCM (12 L). The reaction mixture was stirred at 20 °C for 20 h. TLC indicated that the Tag5-2 reagent was completely consumed, and a new main spot was detected (petroleum ether:ethyl acetate = 10:1, PMA, Rf = 0.61). MTBE (12 L) and silica gel (800 g) were added sequentially to the reaction mixture, which was then stirred for 10 min and filtered through Celite. The filtrate was concentrated under vacuum; The resulting dark brown oil was diluted with petroleum ether (15 L) and passed through a small silica / celite pad (800 g / 400 g) and concentrated to give Tag5-3 (3.13 kg, 6.30 mol, 90.34% yield) as a light yellow solid. 2H NMR (400 MHz, CDCla) δ = 9.74 (s, 1H), 7.04 (s, 2H), 1.00 (s, 9H), 0.96 (s, 18H), 0.26 (s, 12H), 0.16 (s, 6H). LC-MS: (analyzed by method 1) Rt = 3,550 min, m / z = 497.4 [M+H]+.Tag5-3 was used directly for the next step without purification. Step d: Synthesis of Ν,Ν-Bis[[3,4,5-tris[[tertbutyl(dimethyl)silyl]oxy]phenyl]methyl]prop-2-en-l-amine (Tag5-4) TBSO OTBS TBSO Tag5-3a Tag5-3 TBSO OTBS OTBS Tag5-2 Tag5-4

[637] To a solution of Tag5-3a (240 g, 2.51 mol, 98% purity, 1 eq) was added NaOAc (721.82 g, 8.80 mol, 3.5 eq) in THE (8 L) and MeOH (12.5 L), and the mixture was stirred for 30 min under N2, then a solution of Tag5-3 (1.40 kg, 2.77 mol, 98% purity, 1.1 eq) in THF (1.5 L) and HOAc (3.02 kg, 50.28 mol, 2.88 L, 20 eq) were added sequentially at 200°C. The mixture Petition 870260086043, dated 08 / 24 / 2026, pp. 206 / 389 The reaction mixture (201 / 328) was stirred for 30 min. A solution of NaBH3CN (157.98 g, 2.51 mol, 1 eq) in THF (1.5 L) was added dropwise to the reaction mixture over 30 min, then stirred at 25°C for 1 min. An additional solution of Tag5-3 (1.66 kg, 3.27 mol, 98% purity, 1.3 eq) in THF (1.5 L) was added and the reaction was stirred for 30 min. An additional solution of NaBH3CN (236.98 g, 3.77 mol, 1.5 eq) in THF (1.5 L) was added dropwise to the reaction mixture over 1 h, then stirred at 25°C for 12 h. TLC indicated that the Tag5-3 reagent was consumed and a main stain appeared (petroleum ether / ethyl acetate = 20 / 1, staining reagent: PMA, Rf = 0.66). Two impurities, Tag5-2 and Tag5-4' were also detected. The reaction was stopped by the addition of saturated aqueous NaHCO3 (18 L, 3.6 kg of NaHCO3 were suspended in 16 L of H2C) and the separated aqueous solution was then extracted with MTBE (12 L * 2). The combined organic layers were washed with brine (8 L), dried over Na2SC4, filtered and concentrated under reduced pressure to give the crude product (~3.8 kg) as a colorless oil, which was identified by HNMR (ratio of 4:2:4' = 1.0:0.57:0.28). The crude material was mixed with silica gel (4.5 kg) and purified by column chromatography using petroleum ether / ethyl acetate (1 / 0 to 100 / 10) to give Tag5-4 (1.88 kg, 1.73 mol, yield of 71.2% based on 3a). 1H NMR (400 MHz, CDCl3) δ = 6.50 (s, 4H), 6.02 - 5.71 (m, 1H), 5.21 (d, J = 17.6 Hz, 1H), 5.12 (d, J = 10.0 Hz, 1H), 3.37 (br s, 4H), 2.98 (br d, J = 4.8 Hz, 2H), 0.99 (s, 18H), 0.93 (s, 36H), 0.20 (s, 24H), 0.11 (s, 12H). LC-MS: (analyzed by Method 1) Rt= 4.313 min, m / z=1018.6 [M+H]+. Step e: Synthesis of 1-[3,4,5-Tris[[tertbutyl(dimethyl)silyl]oxy]phenyl]-N-[[3,4,5-tris[[tertbutyl(dimethyl)silyl]oxy]phenyl]methyl]methanamine (Tag5-5) Petition 870260086043, dated 08 / 24 / 2026, pp. 207 / 389 202 / 328 CAS NO.: 769-42-6 Pd(PPh3)4(0.05 eq) DCM (10 V) 40 °C, 6 h OTBDMS Tag5-5 OTBDMS OTBDMS OTBDMS

[638] To a solution of 1,3-dimethylbarbituric acid (CAS No.: 769-42-6, 885, 13 g, 5.67 mol, 3.2 eq) in DCM (12.5 L), a solution of Tag5-4 (1.9 kg, 1.77 mol, 95% purity, 1 eq) was added to DCM (4 L). The reaction was degassed and purged 3 times with N2 and then Pd(PPh3)4 (61.41 g, 53.15 mmol, 0.03 eq) was added. The reaction mixture was degassed and purged 3 times with N2 and stirred at an internal temperature of 39°C (oil batch temperature: 45°C) for 4 h under a N2 atmosphere. TLC indicated that the Tag5-4 reagent was completely consumed and a new point (petroleum ether: ethyl acetate = 10:1, NH3.H2O (0.5% v / v), Ninhydrin, Rf = 0.62) was formed. The reaction mixture was cooled to 10°C and stopped by the addition of NH3.H2O (400 mL, wt%: 25%). A white solid precipitated. Sulfhydryl silica gel (350 g), silica gel (700 g) and Na2SO4 (1000 g) were added to the reaction, and the reaction mixture was stirred for 30 min. The reaction mixture was filtered through a Celite buffer (500 g) to give Tag5-5 (1.69 kg, 1.64 mol, 92.6% yield, 95% purity) as yellow oil, which was dissolved in DCM (10 L) and used directly without purification. 1H NMR (400 MHz, CDCl3) δ (ppm) = 6.46 (s, 4H), 3.59 (br s, 4H), 0.99 (s, 18H), 0.96 - 0.87 (m, 36H), 0.20 (s, 24H), 0.12 (s, 12H). LCMS: (analyzed by method 1) Rt = 4.21 min, m / z = 978.5 [M+H]+. Step f: Synthesis of 9H-Fluoren-9-ylmethyl N-[[4-[2[Bis[[3,4,5-tris[[tert-butyl(dimethyl)silyl]oxy]phenyl]methyl]amino]-2-oxo-ethoxy]phenyl]-(2,4dimethoxyphenyl)methyl]carbamate (Tag5-6) Petition 870260086043, dated 08 / 24 / 2026, pp. 208 / 389 203 / 328

[639] To a solution of Tag5-5a (913.17 g, 1.69 mol, 1.13 eq) in DCM (6 L), HOAt (245.71 g, 1.81 mol, 252.53 mL, 1.2 eq) and DIC (227.82 g, 1.81 mol, 279.53 mL, 1.2 eq) were added, and the reaction mixture was stirred at 25 °C for 30 min. Then, a solution of Tag5-5 (1.55 kg, 1.50 mol, 95% purity, 1 eq) in DCM (10 L) was added, and the reaction mixture was stirred at 25 °C for 8 h. TLC indicated that the Tag5-5 reagent was consumed, and a new keystone was detected (petroleum ether:ethyl acetate = 5:1, 4% DCM to improve solubility, Rf = 0.39). The reaction mixture was stopped by the addition of saturated NaHCO3 (5 L*3) and then extracted with DCM (3 L *2). The combined organic layers were washed with brine (2.5 L), dried over Na2SO4, filtered, and concentrated under reduced pressure to generate a residue.The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 20 / 1 to 1 / 1) to give Tag5-6 as a white solid (2.2 kg, 1.25 mol, yield 82.85%, purity 85%). 1H NMR (400 MHz, CDCl3) δ (ppm) = 7.77 (br d, J = 7.3 Hz, 2H), 7.59 (br d, J = 6.4 Hz, 2H), 7.39 (br d, J = 6.6 Hz, 2H), 7.31 (br d, J = 6.4 Hz, 2H), 7.24 - 7.14 (m, 1H), 7.11 - 7.08 (m, 2H), 6.79 (br d, J = 8.5 Hz, 2H), 6.50 - 6.47 (m,. 2H), 6.38 (m, 2H), 6.31 (s, 2H), 6.06 - 5.99 (m, 1H), 5.86 5.72 (m, 1H), 4.66 (s, 2H), 4.46 - 4.38 (m, 4H), 4.29 - 4.19 (m, 3H), 3.81 (s, 3H), 3.74 (s, 3H), 1.00 (s, 18H), 0.92 (s, 36H), 0.19 (s, 24H), 0.13 (s, 12H). LC-MS: (analyzed by Method 1) Rt= 5.39 min, m / z=251.0 [M+6H]6+. Step g: Synthesis of 2-[4-[Amino-(2,4- ... 204 / 328 dimethoxyphenyl)methyl]phenoxy]-Ν,Ν-bis[[3,4,5-tris[[tertbutyl(dimethyl)silyl]oxy]phenyl]methyl]acetamide (Tag5-7) Member5-6 Member5-7

[640] To the Tag5-6 solution (2.2 kg, 1.25 mol, 85% purity, 1 eq) in THF (16 L) was added piperidine (530.63 g, 6.23 mol, 615.44 mL, 5 eq). The reaction mixture was degassed and purged with N2 three times, then stirred at 60°C for 2 h under an N2 atmosphere. TLC demonstrated the formation of a new principal point (petroleum ether:ethyl acetate = 1:1, Rf = 0.16). The reaction mixture was concentrated to yield a crude oil (1.8 kg, 1.18 mol, 94.91% yield, 84% purity) in the form of yellow oil, which was dissolved in DCM (12 L), washed with saturated ammonium chloride (10 L*2), water (10 L) and brine (10 L). It was then dried over Na2SÜ4 and filtered to yield a solution, which was concentrated to yield Tag5-7 (1.8 kg, 94.9% yield and 84% purity). Tag5-7 was used directly in the next step, without purification.1NMR(400 MHz, CDCI3) δ (ppm) 7.27 (br d, J = 8.6 Hz, 2H) , 7.12 (d, J = 8.0 Hz, 1H) , 6.81 (d, J = 8.6 Hz, 2H) , 6.44 (s, 2H) , 6.39 (s, 2H), 6.31 (s, 2H), 5.38 (s, 1H), 4.66 (s, 2H), 4.43 (s, 2H), 4.29 (s, 2H), 3.79 - 3.76 (m, 6H), 1.00 (s,18H), 0.92 (s, 36H), 0.25 - 0.16 (m, 24H), 0.13 (s, 12H). LC-MS: (analisado pelo método 1) Rt= 4,30 min, m / z=1260,7 [M+H-NHa]4. Etapa h: Síntese of alii N-[[4-[2-[Bis[[3,4,5-tris[[terc butil(dimetil)silil]oxy]fenil]metil]amino]-2-oxo-etoxi]fenil] (2,4-dimetoxifenil)metil]carbamato (Tag5-8) Petition: 870260086043, on August 24, 2026, p. 210 / 389 205 / 328

[641] To a solution of Tag5-7 (1.8 kg, 1.18 mol, 84% purity, 1 eq) in DCM (20 L) were added DIEA (305.78 g, 2.37 mol, 412.10 mL, 2 eq) and allyl chloride (285.17 g, 2.37 mol, 250.15 mL, 2 eq). The reaction mixture was stirred at 25°C for 12 h. TLC showed that the starting material was completely consumed, and a new principal point (petroleum ether:ethyl acetate = 5:1, Rf = 0.45) was detected. The reaction mixture was stopped by the addition of saturated NH4Cl (5 L) and then extracted with DCM (5 L * 2). The combined organic layers were washed with saturated NH4Cl (5 L * 2), brine (2 L), and dried over Na2SO4 was filtered and concentrated under reduced pressure to provide the crude product as a yellow oil, which was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 20:1~3:1, 2% DCM was added to the eluent solvent to promote solubility) to provide Tag5-8 in two fractions totaling 1.59 kg (97% yield at >98% purity). Fraction 1 (1.35 kg, 991.02 mmol, 99% purity) yielded 83.78% as a yellow oil. Fraction 2 (380 g, ~80% purity) was further purified to provide 236 g, 160.02 mmol, 98.1% purity as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ (ppm) = 7.10 (br d, J = 8.8 Hz, 3H, 26, 28.37), 6.77 (d, J = 8.6 Hz, 2H), 6.52 - 6.42 (m, 2H), 6.37 (s, 2H), 6.30 (s, 2H), 6.01 - 5.78(m, 3H), 5.30 (br dd, J = 1.6, 17.2 Hz, 1H), 5.21 (br dd, J = 1.3, 10.4 Hz, 1H), 4.64 (s, 2H), 4.61 - 4.58 (m, 2H), 4.42 (s,2H), 4.26 (s, 2H), 3.80 (s, 3H), 3.71 (s, 3H), 0.99 (s, 18H), 0.950.88 (m, 36H), 0.18 (s, 24H), 0.12 (s, 12H). LC-MS: (Método 2) Petition: 870260086043, on August 24, 2026, p. 211 / 389 206 / 328 Rt = 2.22 min, m / z=1379.74 [M+H3O]+; m / z=2741,2 [2M+H3O]+ Etapa i: Síntese de alil N-[[4-[2-[Bis[[3,4,5-tris(docosa1,3,5,7,9,11,13,15,17,19,21-undecainoxi)fenil]metil]amino]-2oxo-etoxi]fenil]-(2,4-dimetoxifenil)metil]carbamato (Tag5-9) Tag5-8 Tag5-9

[642] The 5 reaction batches were conducted in parallel on a 50 g scale. To a mixture of Tag5-8 (50.0 g, 33.80 mmol, 1 eq) and 1-bromodocosane (86.2 g, 206.19 mmol, 6.1 eq) were added K2CO3 (42.1 g, 304.2 mmol, 9 eq), 18-crown-6 (5.4 g, 20.3 mmol, 0.6 eq) and KF (17.67 g, 304.21 mmol, 9 eq). The reaction mixture was degassed and purged 3 times with N2, and then the mixture was stirred at 85°C for 24 h under an N2 atmosphere. LCMS indicated that Tag5-8 was consumed. TLC revealed a new key point (THF / petroleum ether = 1:5, Rf = 0.35). The reaction mixture was suspended in THF (400 mL), filtered through silica gel buffer to remove the inorganic salt, and the filtrate was concentrated to yield a residue. The residue was purified by flash chromatography on silica gel (ISCO®; 330 g SepaFlash® silica flash column, 0-50% THF / petroleum ether gradient eluent: 120 mL / min) to obtain Tag5-9 (76 g, 30.06 mmol, 88.94% yield).

[643] Four additional reactions were conducted and purified as described above. Then, the 5 batches of purified Tag5-9 were combined and ground with MeOH (200 mL, 70°C, 2 h), cooled to 20°C and filtered to yield 386 g of Tag5-9 (purity: ~97.7%) in total. 1H NMR (400 MHz, CDCl3) δ (ppm) = 7.12 (br d, J = 8.5 Hz, 3H), 6.81 (br d, J = 8.6 Hz, Petition 870260086043, dated 08 / 24 / 2026, page 212 / 389 207 / 328 2H), 6.50 - 6.43 (m, 2H), 6.40 (s, 2H), 6.30 (s, 2H), 6.00 (br d, J = 8.8 Hz, 1H), 5.97 - 5.87 (m, 1H), 5.86 - 5.72 (br d, J = 8.6 Hz, 1H), 5.38 - 5.26 (m, 1H), 5.25 -5.08 (m, 1H), 4.71(s, 2H), 4.59 (br d, J = 5.4 Hz, 2H), 4.50 (s, 2H), 4.40 (s,2H), 3.93 (br t, J = 5.7 Hz, 4H), 3.90 - 3.81 (m, 8H), 3.80 (s,3H), 3.72 (s, 3H), 1.82 - 1.68 (m, 12H), 1.53 - 1.20 (m, 228H),0.89 (t, J = 6.8 Hz). LC-MS (Method 3): Rt = 11.33 min, m / z = 2544.7 / 2545.99 [M+HsO]+. NMR data were compared to the target structure using HSQC. The chemical shift at C55 was 69.30 ppm and HMBC:H55 was correlated with C13. Step j: Synthesis of 2-[4-[Amino-(2,4 dimethoxyphenyl)methyl]phenoxy]-N,N-bis[[3,4,5tri(docosoxy)phenyl]methyl]acetamide (Tag5) Pd(PPh3)4 (0.05 eq) 1,3-dimethylbarbituric acid Tag5-9 DCM (10 V) 40 °C, 6 h Tag 5-10

[644] A solution of 1,3-dimethylhexahydropyrimidine-2,4,6-trione (15.3 g, 97.7 mmol, 3.2 eq) in DCM (560 mL) was added Tag5-9 (80 g, 30.54 mmol, 1 eq) was degassed and purged three times with N2, and then Pd(PPh3)4 (1.41 g, 1.22 mmol, 0.04 eq) was added. The mixture was degassed and purged three times with N2 and stirred at 45°C for 6 h under a N2 atmosphere. TLC indicated that Tag5-9 was consumed, and a new significant smudge (petroleum ether: THF = 1:1, Rf = 0.14, PMA) was detected. The reaction was concentrated and the residue ground in MeOH (1 L) at 70°C for 1 h, then cooled to 20°C. The mixture was filtered to provide a crude product, which was subsequently ground in ACN (1 L, 70°C, 1 h), cooled to 20°C, filtered, and washed with ACN (400 mL), MeOH (400 mL), EtOAc (400 mL), and ether. Petition 870260086043, dated 08 / 24 / 2026, pp. 213 / 389 208 / 328 petroleum (400 mL) sequentially, and then vacuum dried to provide Tag5 (74.8 g, 29.32 mmol, 95.99% yield, 95.79% purity) as a whitish solid. Four additional repeat reactions were conducted as described above to generate total Tag5 (303.9 g with 95.5% purity) .1H NMR (400 MHz, CDCl3) δ (ppm) 7.14 - 7.25 (m, 2 H), 7.03 (br d, J=7.75 Hz, H), 6.76 (br d, J=8.25 Hz, 2 H), 6.34 (br d, J=12.38 Hz, 4 H), 6.22 (br s, 2 H), 5.30 (br s, 1 H), 4.65 (s, 2 H), 4.23 - 4.50 (m, 4 H), 3.63 - 3.96 (m, 18 H), 1.67 (br d, J=5.50 Hz, 12 H), 1.37 (br s, 12 H), 1.18 (s, 216 H), 0.81 (br t, J=6.44 Hz, 18 H) ppm.13C NMR (101 MHz, CDCL·) δ = 168.42, 159, 83, 157, 67, 156, 74, 153.62, 153.27, 137.65 - 137.58, 137.58 - 137.50, 131.79, 131.09, 128.17, 128.07, 114.29, 107.04, 105.04, 104.00, 98.74, 77.25 73.48, 73.43, 69.18, 69.14, 67.75, 55.37, 55.34, 52.88, 49.67 48.50, 31.97, 30.42, 29.77, 29.71, 29.57, 29.51, 29.42, 26.23 22.74, 14.16. LC-MS (Method 3): Rt = 11.20 min, m / z=2444.02 [M+H]+. 8.2 Characterization of Tag5

[645] The characterization of Tag5 is shown in Table 10. Chemical Formula: C163H298N2O10 Exact Mass: 2442.27 TAG-5 Table 10. Characterization of Tag5 Compound ID Tag5 Exact Mass 2442.27 State Whitish Solid Petition 870260086043, dated 08 / 24 / 2026, page 214 / 389 209 / 328 Stability Stability under different pH Overall yield 25% yield for 10-step synthesis with HPLC purity >95% for 400g production, using 3 chromatographic purifications in steps d, f, h IUPAC 2-(4-(amino(2,4-dimethoxyphenyl)methyl)phenoxy)-N,Nbis(3,4,5-tris(docosyloxy)benzyl)acetamide SMIL O = C CCCCCCC)=C(OCCCCCCCCCCCCCCCCCCCCCC)C(OCCCCCCCCCCCCCCC CCCCCCCC)=C4 IR data

[646] The Tag5 powder sample was placed directly onto the ATR surface, while the surface of the ATR crystal (Znse) was completely covered by the sample. A compression rod was used to compress the sample, distributing it evenly and keeping it in full contact with the ATR crystal surface. The IR conditions used to collect the IR data are shown in Table 11. Table 11. IR Conditions Parameter Value Instrument Manufacturer Term Instrument Model NICOLET iS10 Sample Preparation Mode KBr Disc Method Parameters 40°C Detector: DTGS KBr Resolution: 4 Beam Splitter: KBr Sample Gain: 1 Source: IR Optical Speed: 0.4747 Number of Sample Scans: 16 Aperture: 150 Number of Background Scans: 16

[647] λ = 2915.54 cm-1 indicated CH(CH3) bonding; λ = 2848.94 Petition 870260086043, dated 08 / 24 / 2026, pp. 215 / 389 210 / 328 cm-1 indicated a CH (CH2) bond; λ = 1647.99 cm-1 indicated a C=O (C=ONR2) bond; λ = 1505.99 cm-1 indicated a CN bond; λ = 1466.52 cm-1 indicated a C=C (Ph) bond; λ = 1379.34 cm-1 indicated a CH(CH3) bond; and λ = 1174.13 cm-1 indicated a COC bond. Determination of moisture content

[648] The sample was weighed into a dry, clean flask. The flask was sealed. After the instrument reached the preset temperature (150 °C), the flask was placed in the oven. After the Karl Fischer reaction was complete, the water content of the sample was obtained (Table 12). The moisture content was determined to be 0.26%. Table 12. Conditions used to determine the moisture content in the sample. Parameter Value Extraction time 30 seconds Drift start 25 μg / min Stop criteria Relative Drift Stop 5 μg / min Anode solution HYDRANAL / Coulomat AK Cathode solution HYDRANAL / Coulomat CG-K Stirring speed 45% Atmosphere Dry air Gas flow rate 80 mL / min Bottle volume 10 L Ion Chromatography

[649] The chromatographic conditions used are shown in Tables 12-13. The following ion contents were Petition 870260086043, dated 08 / 24 / 2026, pp. 216 / 389 211 / 328 determined: Cl-: 0.01%; Br-: 0.01%; F-: < 0.01%; CO32-: 0.02%. Table 13. F-ion chromatography conditions Instrument Name: ICS-6000 Mobile Phase: KOH Flow Rate: 1.0 mL / min Guard Column: Dionex IonPac AG18, 4*50 mm Column: Dionex IonPac AS18, 4*250 mm Column Temperature: 30°C Cell Temperature: 35°C Detection Mode: Conductivity Detection Suppressor Current: 99 mA Injection Volume: 25 μL Analysis Time: 16 minutes KOH Concentration Time KOH Concentration 0 5 6 5 8 40 12 40 12.1 5 16 Stop Table 14. Chromatography conditions for Cl-, Br-, CO32 ions Instrument Name: ICS-6000 Mobile Phase: Isocratic KOH 25 mM Flow Rate: 1.0 mL / min Guard Column: Dionex IonPac AG11-HC, 4*50 mm Column: Dionex IonPac AS11-HC, 4*250 mm Column Temperature: 30 °C Cell Temperature: 35 °C Detection Mode: Conductivity detection Suppressor Current: 62 mA Injection Volume: 25 μL Analysis Time: 10 min Differential Scanning Calorimeter

[650] The sample (1-8 mg) was placed in a high-temperature crucible. Petition 870260086043, dated 08 / 24 / 2026, pp. 217 / 389 212 / 328 pressure and sealed with the corresponding tool. The prepared sample was placed in the corresponding position of the instrument, the parameters in the software were selected and the execution sequence was initiated (Table 15).

[651] The first peak (melting point, endothermic) was observed at 76.3°C. The second peak (C22 must be volatile, endothermic) was at ~371°C. Table 15. Differential Scanning Calorimeter (DSC) Conditions Parameter Value Instrument Differential Scanning Calorimeter Instrument Model DSC 214 Manufacturer NETZSCH Crucible Type Gold-plated high-voltage crucible Gas Nitrogen Flow Rate 100 mL / min Temperature Program Initial Temperature / °C Heating Rate / K / min Final Temperature / °C 30 10 400 Determination of Residual Solvent (RS)

[652] Residual solvent (GC and HS conditions) is shown in Table 16. Instrument: SHIMADZU-GC2030 and HS-20. The column used for chromatography was DB-624 (25 m x 0.2 mm, ID 1.12 μm). P / N: 128-1324. Split ratio: 30. Control mode: Linear velocity. Flow rate: 1.2 mL / min. Carrier gas: N2. Detector: Flame Ionization Detector (FID). All solvent residues were found below the limit of quantification (LOQ). Table 16. Residual solvent conditions Parameter Value Detector temperature: 260 °C Petition 870260086043, dated 08 / 24 / 2026, pp. 218 / 389 213 / 328 Carrier gas flow (N2): 30 mL / min H2 flow: 40 mL / min Air flow: 400 mL / min Column temperature Rate Temperature Holding time 45 °C 0.2 minutes 2 °C / minute 50 °C 0.0 min 35 °C / minute 250 °C 3.3 minutes Running time: 11.7 minutes Free space method: Oven temperature Sample line temperature TR line temperature 110 °C 150 °C 180 °C Equilibration time: 10 min Sample concentration: 100 mg / mL Diluent: 1,3-Dimethyl-2-imidazolidinone Solubility test

[653] Tag5 (10 mg) was added to the solvent (100 pL) and stirred at different temperatures (Table 17). Tag5 was found to be soluble in DCM and THF, PE / DCM and PE / THF in any proportion, except in DMF and DMF / DCM, and not in DMSO and DMSO / DCM (see Table 17). Table 17. Solubility of Tag5 in organic solvents. Solvent No. Solubility Ratio (%) Petition 870260086043, dated 08 / 24 / 2026, pp. 219 / 389 214 / 328 25 °C 40 °C 1 DCM 100% clear clear 2 THF / DCM 10% clear clear 3 THF / DCM 20% slightly clear clear 4 THF / DCM 30% slightly clear clear 5 THF / DCM 40% slightly clear clear 6 THF / DCM 50% slightly clear clear 7 THF / DCM 60% slightly clear clear 8 THF / DCM 70% slightly clear clear 9 THF / DCM 80% slightly clear clear 10 THF / DCM 90% slightly clear clear 11 THF 100% clear clear 12 DMF / DCM 10% slightly clear slightly clear 13 DMF / DCM 20% slightly clear slightly clear 14 DMF / DCM 30% slightly clear slightly clear 15 DMF / DCM 40% slightly clear slightly clear 16 DMF / DCM 50% slightly clear slightly clear 17 DMF 100% slightly unclear 18 DMSO / DCM 10% slightly unclear 19 DMSO / DCM 20% slightly unclear 20 DMSO / DCM 30% slightly unclear 21 DMSO / DCM 40% slightly unclear 22 DMSO / DCM 50% slightly unclear 23 DMSO 100% slightly unclear 24 PE / DCM 10% clear clear 25 PE / THF 10% clear clear Stability Test

[654] The stability test for Tag5 was performed at pH = 2 for 2 hours using the following procedure. Tag5 (1 g, 98.01% purity) was added to a 50 mL flask with a magnetic stir bar in THF (20 mL) and the mixture was stirred for 5 minutes to dissolve the material. A solution of TFA in DCM (v / v = 1:5, 2 mL) was added dropwise to the solution containing Tag5 to reach pH 2, and the resulting solution was stirred continuously for 2 hours. The reaction was monitored by LCMS, which Petition 870260086043, dated 08 / 24 / 2026, pp. 220 / 389 215 / 328 showed more than five peaks. It was concluded that Tag5 is not very stable in acidic solution (pH = 2). 8.3 Synthesis (LPPS) of a GLP1 Peptidomimetic in Tag5

[655] The synthesis of a GLP1 (Ml) peptidomimetic in Tag5 is shown in Figures 6 and 10A-B and in Table 18. The amino acids used to prepare this peptidomimetic are shown in Table 19. Table 18 Produced # MS structure connected (Μ+Η) + Calculation MF / MW after divagem de Tag5 1AA or ΛΑ NHj 221,1 [M-TAG+2H]+ C13H20N2OH / 221,17 NFmoc -1ΆΑ or ΛΑ HNV γ Fmoc 443,2 [M-TAG+2H]+ C28H30N2O3H 443.24 2AA ζ ω Ο / “A va* £ \ ' ο Ο- ΙΖ _ / ο=(^ Ζ ζ W Ο Λα Ο=\ i1 < ζχ \__ χζ __ / ζ Petition 870260086043, 08 / 24 / 2026, pág. 221 / 389 216 / 328 3AA z ta O 1 o}= / z ^-O / \__ \ / tT 0 í H o ^jQT 922,5 [M-TAGtBu+3H]+ C53H59N7O8H 922,45 4AA « JQ, HsN xÍvVyh2 o Z o 787,4 [M-TAG- tBu- TBS+4H]+ C41H54N8O8H / 787'4 NFmoc -4ΆΑ oh JL JL Ao FmocHN^Ã AnH, > HS à Η π H0 1009,4 [M- TAG-tBu- TBS+4H]+ C56H64N8O10H 1009,48 5AA 0H AqA, X j\ÍkAVh. 0 3H M ° £T «.^^0XXi 1002,7 [M-TAG- tBu- TBS+4H]+ C51H75N9O10SÍH / 1002,55 Petition 870260086043, 08 / 24 / 2026, pág. 222 / 389 217 / 328 NFmoc -5ΆΑ 7 < o \ z / z / > O=( OO ZI 1 O í X ' 0=2 XXX. 0 '-r0H0 |. 0 Q / η2ν4αΧκ^Χ^,νΛ^νη2 £ H II H II H II XÁ ογ™ ο Λ o} FmocHNjA^N^^Njt^NH, vq 0 S>hH °j H 0 1290,8 [M-TAG- tBu- 2TBS+5H]+ C7oH8iFNioOi3H 1289, 61 7AA ΧΑΧ^Χυ^Χ· 0 k 0 Oi 0 Γ ll K 1282.7 [M-TAG- tBu- 2TBS+5H]+ CgsHgzFNiiOisSiH / 1282.67 NFmoc -7ΆΑ 0H xX-X FmocHX^X^A^AX™' or xJk 0 0 0 n OH _ j ,OX 1390.5 [M-TAG- tBu3TBS+6H]+ C74H88FNiiOi5H 1390.65 8AA « A Λ Κ>θΗ Λ Petition 870260086043, 08 / 24 / 2026, pág. 223 / 389 218 / 328 NFmoc -8AA OH JUx 1447.6 [M-TAG- tBu- 3TBS+6H]+ C76H91FN12O16H 1447.68 9AA ο Ο 0 OH 0 = 0 1' M 1364.7 [M-TAG- tBu-3TBS- DMB+7H]+ C65H86FNi7Oi5H / 1364.66 NFmoc -9AA hn-n OH 1χ 'O 794.2 [M- TAG-tBu- 3TBS- DMB+8H]2+ C80H96FN17O17H, 1586.74 [M-TAG-tBu- 3TBS-DMB+7H]+, C80Hg6FNi7O17H2, 793, 87 [M-TAG-tBu-3TBS- DMB+8H]2+ 10AA HH'H Ο JX. Á Ϊ ? ÁXYXT- ? f ϊ f * sVXaV XXl 'ou λ = ' X 786.7 [M- TAG-tBu- 3TBS-DMB- Trt+9H]2+ C75H99FN20O17H2 Tag5- M1 hn-n OH 'ΎΧι oh „ = X fr Ο-ν,^Ο-^ΝΗ, n „ 990.4, [M-Tag5- tBu-3TBSDMB-TrtBoc+IOH]2 + C94H136FN21O25H2, 990.01, [M-Tag5-tBu- 3TBS-DMB-Trt- Boc+IOH]2+ Ml 990.5, [M+2H]2+ C94H136N21O25FH2, 990.01, [M+2H]2+ AA10- AA9- AA8 HN-N Table 19 Cpd # Structure No. Source ★ MF / MW ESI-MS M / Z IUPAC Name Petition 870260086043, 08 / 24 / 2026, pág. 224 / 389 219 / 328 AA1 0 Yyγ oh / J NHFmoc CAS n° 21040 3158-3a, b C28H29NO4 443.2 466.1 [M+Na]+ Acid (2S)-5-(3,5- dimethylphenyl)-2-(9H-fluoren9ylmethylmethylphenylic acid)A γυΧοη X / A / NHFmx b C36H36N4O5 604.2 627.3 [M+Na]+ Acid (2S)-3-[4-[4-(4- azidobutoxy)-2-ethyl- phenyl]phenyl]-2-(9H-fluorenine9-oxylamine anoxic acid) 1 O NHFmoc C23H25NO6 411, 1 412.1 [M+H]+ Acid (2S)-4-terc-butoxy-2- (9H-fluorene-9- ylmethoxycarbonylamino)-4- oxo-butanoic AA4 1 0 Ά / xis VH / γγ NHγγ C22H25NO5 383.1 384.1 [M+H]+ Acid (2S)-3-[terc- butyl(dimethyl)silyl]oxi-2- (9H-fluorene-9- ylmethoxycarbonylamino)propane oico TBS- AA4 \ / II >slo^oh ' NH 442.2 [M+H]+ Acid (2S)-3-[terc- butyl(dimethyl)silyl]oxy-2- (9H-fluorene-9- ylmethoxycarbonylamino)propane oico AA5 1 Ξ ° / oyoH NHFmoc C23H27NO5 397.1 [M+H]+, 398 N-H (((9H-fluorene-9- yl)methoxy)carbonyl)-O-(tercbutyl)-L-threonine TBS- AA5 >fsi.o^ykOH ' NHFmoc C25H33NO5SÍ 455.21 456.22 [M+H]+ Acid (2S,3R)-3-[tert- butyl(dimethyl)silyl]oxy-2(9H-fluoren-9ylmethoxycarbonylamino)butanoic AA6 O i|j OH NHFmoc C25H22FNO4 419, 1 420.1 [M+H]+ Acid (2S)-2-(9H-fluoren-9- ylmethoxycarbonylamino)-3-(2fluorophenyl)-2-methylpropanoic AA7 1 Ξ 0 / A / kisA Y^oy^OH NHFmoc C23H27NO5 397.1 398.1 [M+H]+ Acid (2S,3R)-3-[tert- butyl(dimethyl)silyl]oxy-2-(9H-fluoren-9- ylmethoxycarbonylamino)butane ico. Petition 870260086043, 8 / 24 / 2026, p. 225 / 3 220 / 3 TBS- AA7 \ / í 9 ' NHFmoc C25H33NO5SÍ 455.21 456.22 [M+H]+ N-(((9H-fluoren-9-il)metoxi)carbonil)-0-(tercbutyldimetilsilyl)-Ltreonina ΆΑ8 O FmocHN^ / kOH C17H15NO4 297.1 298.1 [M+H]+ Ácido 2-(9H-fluoren-9ilmetoxicarbonilamino)acétic 0 AA9 H ? o 'nN NHFmoc CAS n° 27650 6545-8b C28H27N5O6 529,20 530, 4 [M+H]+ Ácido (2S)-3-[1-[ (2,4- dimetoxifenil)metil]tetrazol -5-il]-2-(9H-fluoren-9ilmetoxicarbonilamino)propan oico AA10 zTrt / 'NO 0 CAS n° 21318 3060-7b C29H30N3O3 468,2 468,1 [M+H]+ Ácido 2,2-dimetil-3-oxo-3[2-(3-tritilimidazol-4il)etilamino]propanoico N- Boc- NH- PEG8- alcino BocHnC^0L·^^ o CAS n° 11967 3252-ld C24H45NO10 507,30 508,3 [M+H]+ terc-butil N-[2-[2-[2-[2-[2[2- [2- (2-prop-2- inoxietoxi)etoxi]etoxi]etoxi ]etoxi]etoxi]etoxi]etil] carbamato NH2- PEG8alcino h2n^o^o CAS n° 11967 3252-1 C19H37NO8 407,30 408,3 [M+H]+ 3,6,9,12,15,18,21,24octaoxaheptas-2 6-in-lamina, aGB2551945 for Andrews et al., which is incorporated herein by reference in its entirety; bWO2022 / 056494 for Han et al., which is incorporated herein by reference in its entirety; cSureshbabu et al., Synthesis of Tetrazole Analogues of Amino Acids Using Fmoc Chemistry: Isolation of Amino Free Tetrazoles and their incorporation into peptides, Tetrahedron Lett. 48(39):7038-7041 (2007), which is incorporated herein by reference in its entirety. Petition 870260086043, dated 08 / 24 / 2026, pp. 226 / 389 221 / 328 dMurelli et al., “Chemical Control Over Immunological Recognition: A Class of Small Antibody Recruitment Molecules Targeting Prostate Cancer”, J. Am. Chem. Soc. 131(47):17090-17092 (2009), which is incorporated herein by reference in its entirety. General procedure H for amide coupling to give NFmoc-Tag5-nAA

[656] To a mixture of Tag5 or Tag5-(n-1)AA (1 eq.) in DCM (50 V) were added AAn (1.5 eq.), HOAt (1.5 eq.) and DIC (1.5 eq.). The resulting suspension was stirred at 20 °C for 2 h. A small sample of the reaction mixture was taken, suspended with ACN and centrifuged twice (3 min at 6000 rpm). The precipitate formed was dissolved in 1 drop of DCM, cleaved using TFA / TIPS / H2O (95 / 2.5 / 2.5), diluted with MeOH / H2O (2 / 1) and filtered. The filtrate was checked by LCMS to confirm the desired mass. The reaction was concentrated under reduced pressure to provide a residue, which was added to ACN / MeOH (2 / 1, 60 V) and stirred for 1 h. The suspension was filtered and washed twice with ACN (10 V). The precipitate was collected and used directly in the next step, without any further purification. The desired compound, N-Fmoc-Tag5-nAA, was obtained as a white solid. General Procedure I for Deprotecting Fmoc to Prepare Tag5-nAA

[657] A clear solution of N-Fmoc-Tag5-nAA (1 eq.) in 20% piperidine / THF (20 V) was stirred at 50 °C for 0.5 h. A small amount of the sample was suspended with CAN and centrifuged twice (3 min at 6000 rpm). The precipitate was collected, redissolved in 1 drop of DCM, cleaved using TFA / TIPS / H2O (95 / 2.5 / 2.5), diluted with MeOH / H2O (2 / 1) and filtered. The filtrate was checked by LCMS to confirm the completion of the reaction. The reaction was concentrated under reduced pressure to generate a residue, which was added to ACN / MeOH (2 / 1, 60 V) and stirred for 1 h. The suspension was filtered and washed twice with ACN (10 Petition 870260086043, dated 08 / 24 / 2026, pp. 227 / 389 222 / 328 V). The precipitate was collected and used directly in the next step, without any further purification. The desired compound Tag5-nAA was obtained as a white solid. Step a: Synthesis of 9H-Fluoren-9-ylmethyl N-[(IS)-1-[[[4-[2[Bis[[3,4,5-tris(docosa-1,3,5,7,9,11,13,15,17,19,21undecainoxy)phenyl]methyl]amino]-2-oxo-ethoxy]phenyl]-(2,4-dimethoxyphenyl)methyl]carbamoyl]-4-(3,5-dimethylphenyl)butyl]carbamate (N-Fmoc-Tag5-1AA) Tag5 N-Fmoc-Tag5-1AA

[658] The reaction was carried out using the general H procedure for amide coupling using Tag5 (1 g, 409.15 pmol, 1 eq), AA1 (2 72 mg, 0.62 mmol, 1.5 eq), HOAt (84 mg, 0.62 mmol, 1.5 eq) and DIC (77 mg, 0.62 mmol, 95.1 pL, 1.5 eq). The reaction was monitored by LC-MS. N-Fmoc-Tag5-1AA (1.18 g, 344.59 pmol, yield 84.22%) was obtained as a white solid. LC-MS: RT = 5.17 min, calculated mass for C28H30N2O3H 443.24, m / z found 443.2 [MTAG+2H] + . Step b: Synthesis of (2S)-2-Amino-N-[[4-[2-[bis[[3,4,5tris(docosa-1,3,5,7,9,11,13,15,17,19,21undecainoxy)phenyl]methyl]amino]-2-oxo-ethoxy]phenyl] - (2,4dimethoxyphenyl)methyl]-5-(3,5-dimethylphenyl) Pentanamide (Tag51AA) Petition 870260086043, dated 08 / 24 / 2026, pp. 228 / 389 223 / 328 N-Fmoc-Tag5-1AA Tag5-1AA

[659] The reaction was carried out using general procedure I for deprotection of Fmoc. A clear solution of the compound NFmoc-Tag5-1AA (1.16 g, 404.24 pmol, 1 eq) in 20% piperidine / THF (20 mL) was stirred at 50°C for 0.5 h. The reaction was monitored by LC-MS. Tag5-1AA (1.06 g, 400.40 pmol, 99.05% yield) was obtained as a white solid. LC-MS: RT = 2.10 min, calculated mass for C13H20N2OH 221.17, m / z found 221.1 [M-TAG+2H] + . Step c: Synthesis of 9H-Fluoren-9-ylmethyl N-[ (IS)-1-[ [4-[4(4-azidobutoxy)-2-ethyl-phenyl]phenyl] methyl]-2-[[(lS)-1-[[[4 —[2 — [bis[[3,4,5-tris(docosa-1,3,5,7,9,11,13,15,17,19,21undecainoxy)phenyl] methyl]amino]-2-oxo-ethoxy]phenyl] - (2,4dimethoxyphenyl)methyl]carbamoyl]-4-(3,5-dimethylphenyl) butyl]amino]-2-oxo-ethyl]carbamate (N-Fmoc-Tag5-2AA) Tag5-1AA

[660] The reaction was carried out using the general H procedure for amide coupling. To a mixture of Tag5-1AA compound (1.06 g, 400.40 pmol, 1 eq) in DCM (40 mL) were added AA2 (363 mg, 600.6 pmol, 1.5 eq), HOAt (81.7 mg, 0.6 mmol, 84 pL, 1.5 eq) and DIC (76 mg, 0.6 mmol, 93 pL, 1.5 eq). The resulting suspension was stirred at 20 °C for 2 h. N-Fmoc-Tag5-2AA (1.25 g, 386.51 pmol, 96.53% yield) was obtained as a solid. Petition 870260086043, dated 08 / 24 / 2026, pp. 229 / 389 224 / 328 white. LC-(ESI) :MS RT = 6.72 min, mass calculated for C49H54N6O5H 807.43, m / z found 807.4 [M-TAG+2H]+. Step d: Synthesis of (2S)-2-[[(2S)-2-Amino-3-[4-[4-(4azidobutoxy)-2-ethyl-phenyl]phenyl]propanoyl] amino]-N-[[4-[2[bis[[3,4,5-tris(docosa-1,3,5,7,9,11,13,15,17,19,21undecainoxy)phenyl]methyl] amino]-2-oxo-ethoxy]phenyl] - (2,4dimethoxyphenyl)methyl]-5-(3,5-dimethylphenyl)pentanamide (Tag5-2AA) Tag5-2AA

[661] The reaction was carried out using general procedure I for Fmoc deprotection. A clear solution of the compound NFaioc-Tag5-2AA. (1.25 g, 386.51 pmol, 1 eq) in 20% piperidine / THF (25 mL) was stirred at 50 °C for 0.5 h. Tag5-2AA (1.15 g, crude) was obtained as a white solid. LC-MS: RT = 4.46 min, calculated mass for C34H44N6O3H 585.36, m / z found 585.4 [M-TAG+2H]+. Step e: Synthesis of tert-Butyl (3S)-4-[[(IS)-1-[[4-[4-(4azidobutoxy)-2-ethyl-phenyl]phenyl]meth1]-2-[[(lS)-l-[[[4 —[2 — [bis[[3,4,5-tris(docosa-1,3,5,7,9,11,13,15,17,19,21undecainoxy)phenyl]methyl]amino] -2-oxo-ethoxy]phenyl] - (2,4dimethoxyphenyl)methyl]carbamoyl]-4-(3,5dimethylphenyl)butyl]amino]-2-oxo-ethyl]amino]-3-(9H-fluoren-9ylmethoxycarbonylamino)-4-oxo-butanoate (N-Fmoc-Tag5-3AA)

[662] The reaction was carried out using the general procedure Petition 870260086043, dated 08 / 24 / 2026, pp. 230 / 389 225 / 328 H for amide coupling. A mixture of Tag5-2AA compound (1.15 g, 381.83 pmol, 1 eq) in DCM (60 mL), AA3 (235.5 mg, 0.57 mmol, 1.5 eq), HOAt (78 mg, 0.57 mmol, 80.1 pL, 1.5 eq) and DIC (72.3 mg, 0.57 mmol, 88.7 pL, 1.5 eq) was used. The resulting suspension was stirred at 20 °C for 2 h. N-Fmoc-Tag53AA (1.3 g, 381.76 pmol, 99.98% yield) was obtained as a white solid.

[663] LCMS (CR) Condition: Reversed-phase LCMS was performed using a NanoChrom ChromCore 120 C18 3µm, 3.0*30mm column, with a flow rate of 1.5 mL / min, eluting with a gradient of 10% to 80% ACN containing 0.02% TFA (solvent B) and water containing 0.04% TFA (solvent A).

[664] LC-MS: RT = 6.25 min, calculated mass for C53H59N7O8H 922.45, m / z found 922.4 [M-TAG-tBu+3H] +.

[665] LCMS (BF) Condition: Reversed-phase LCMS was performed using an Xtimate C18 2.1*30mm 3um column, with a flow rate of 1.5 mL / min, eluting with a gradient of 10% to 80% ACN containing 0.02% TFA (solvent B) and water containing 0.04% TFA (solvent A). Step f: Synthesis of tert-Butyl (3S)-3-amino-4-[[(IS)-1-[[4[4-(4-azidobutoxy)-2-ethyl-phenyl]phenyl] methyl]-2-[[(lS)-l-[[[4[2-[bis[[3,4,5-tris(docosa-1,3,5,7,9,11,13,15,17,19,21undecainoxy)phenyl] methyl]amino]-2-oxo-ethoxy]phenyl] - (2,4dimethoxyphenyl)methyl]carbamoyl]-4-(3,5-dimethylphenyl)butyl]amino]-2-oxo-ethyl]amino]-4-oxo-butanoate (Tag5-3AA) N-Fmoc-Tag5-3AA Tag5-3AA

[666] The reaction was carried out using the general procedure I for Fmoc deprotection. A clear solution of the compound NPedição 870260086043, dated 08 / 24 / 2026, page 231 / 389 226 / 328 .Fínoc-Tag5-3AA (1.30 g, 381.76 pmol, 1 eq) in 20% piperidine / THF (26 mL) was stirred at 50 °C for 0.5 h. The compound Tag5-3AA (1.2 g, 377.00 pmol, 98.75% yield) was obtained as a white solid.

[667] LC-MS: RT = 4, 646 min, mass calculated for C38H49N7O6H 700.38, m / z found 700.5 [M-TAG-tBu+3H] +; RT = 5, 065 min, mass calculated for C42H57N70eNa 778.43, m / z found 778.5 [MTAG+2H+Na] + . Step g: Synthesis of tert-Butyl (3S)-4-[[(IS)-1-[ [4-[4-(4azidobutoxy)-2-ethyl-phenyl]phenyl]methi1]-2-[[(lS)-l-[[[4 —[2 — [bis[[3,4,5-tris(docose-1,3,5,7,9,11,13,15,17,19,21undecainoxy)phenyl]methyl]amino] -2-oxo-ethoxy]phenyl] - (2,4dimethoxyphenyl)methyl]carbamoyl]-4-(3,5dimethylphenyl)butyl]amino]-2-oxo-ethyl]amino]-3-[[(2S)-3-[tercbutyl(dimethyl)silyl]oxy-2-(9H-fluorene-9-ylmethoxycarbonylamino) propanoyl]amino]-4-oxo-butanoate (N-Fmoc-Tag5-4AA) N-Fmoc-Tag5-4AA

[668] The reaction was carried out using the general H procedure for amide coupling. To a mixture of Tag5-3AA compound (1.1 g, 345.59 pmol, 1 eq) in DCM (50 mL) were added TBSAA4 (22.9 mg, 0.52 mmol, 1.5 eq), HOAt (70.5 mg, 0.52 mmol, 1.5 eq) and DIC (65.4 mg, 0.52 mmol, 80.3 pL, 1.5 eq). The resulting suspension was stirred at 20 °C for 2 h. The reaction was monitored by LC-MS. The N-Einoc-Tag5-4AA compound (1.06 g, 293.91 pmol, 85.05% yield) was obtained as a white solid.

[669] LC-MS: RT = 6.01 min, mass calculated for C56H64N8O10H 1009.48, m / z found 1009.4 [M-TAG-tBu-TBS + 4H]+. Condition LCMS (BF): Reversed-phase LCMS was performed using an Xtimate C18 2.1*30mm 3µm column, with a flow rate of 1.5 mL / min, eluting... Petition 870260086043, dated 08 / 24 / 2026, pp. 232 / 389 227 / 328 with a gradient of 10% to 80% ACN containing 0.02% TFA (solvent B) and water containing 0.04% TFA (solvent A). Step h: Synthesis of tert-Butyl (3S)-3-[[(2S)-2-amino-3[tert-butyl(dimethyl)silyl]oxy-propanoyl]amino]-4-[[(IS)-1-[[4[4-(4-azidobutoxy)-2-ethyl-phenyl]phenyl]m ethyl]-2-[[(lS)-l-[[[4[2-[bis[[3,4,5-tris(docosa-1,3,5,7,9,11,13,15,17,19,21undecainoxy)phenyl]methyl]amino]-2-oxo-ethoxy]phenyl] - (2,4dimethoxyphenyl)methyl]carbamoyl]-4-(3,5dimethylphenyl)butyl]amino]-2-oxo-ethyl]amino]-4-oxo-butanoate (Tag5-4AA) N-Fmoc-Tag5-4AA Tag5-4AA

[670] A clear solution of the compound N-Fmoc-Tag5-4AA (1.05 g, 291.13 pmol, 1 eq) in 20% piperidine / THF (20 mL) was stirred at 50 °C for 0.5 h. Following generic precipitation procedures, the desired compound Tag5-4AA (985 mg, 291.05 pmol, 99.97% yield) was obtained as a white solid.

[671] LC-MS: RT = 4.24 min, calculated mass for C41H54N8O8H 787.42, m / z found 787.4 [M-TAG-tBu-TBS+4H]+; RT = 5.10 min, calculated mass for C47H68N8O8SIH 901.50, m / z found 901.5 [M-TAG-tBu+3H]+. LCMS Condition (BF): Reversed-phase LCMS was performed using an Xtimate C18 2.1*30mm 3um column, with a flow rate of 1.5 mL / min, eluting with a gradient of 10% to 80% ACN containing 0.02% TFA (solvent B) and water containing 0.04% TFA (solvent A). Step i: Synthesis of tert-Butyl (3S)-4-[[(IS)-1-[[4-[4-(4-azidobutoxy)-2-ethyl-phenyl]phenyl]methyl]-2-[[(lS)-l-[[[4 —[2 — [bis[[3,4,5-tris(docosa-1,3,5,7,9,11,13,15,17,19,21undecainox)phenyl]methyl]amino]-2-oxo-ethoxy]phenyl]-(2,4-dimethoxyphenyl)methyl]carbamoyl]-4-(3,5-Petition 870260086043, dated 24 / 08 / 2026, p. 233 / 389 228 / 328 dimethylphenyl)butyl]amino]-2-oxo-ethyl]amino]-3-[[(2S)-3-[tertbutyl(dimethyl)silyl]oxy-2-[[(2S,3R)-3-[tertbutyl(dimethyl)silyl]ox-2-(9H-fluoren-9ylmethoxycarbonylamino)butanoyl]amino]propanoyl]amino]-4-oxobutanoate (N-Fmoc-Tag5-5AA)

[672] To a mixture of the compound Tag5-4AA (985 mg, 291.05 pmol, 1 eq) in DCM (50 mL), TBS-AA5 (2S,3R)-3-[tert-butyl(dimethyl)silyl]oxy-2-(9H-fluoren-9ylmethoxycarbonylamino)butanoic acid (199 mg, 0.44 mmol, 1.5 eq), HOAt (59.4 mg, 0.44 mmol, 1.5 eq) and DIG (55 mg, 0.44 mmol, 67.6 pL, 1.5 eq) were added. The resulting suspension was stirred at 20 °C for 2 h. Following generic precipitation procedures, the compound NFmoc-Tag5-5AA (1.05 g, 274.73 pmol, 94.39% yield) was obtained as a white solid.

[673] LC-MS: RT = 5.91 min, calculated mass for C60H71N9O12H 1110.53, m / z ...

Claims

CLAIMS 1. Compound characterized by having a structure of Formula (I): wherein: men are independently an integer from 1 to 5, and (m+n)>3; R1 is a C1-5 alkyl; R2 is independently in each occurrence an optionally substituted C10-30 alkyl; and R3 is independently in each occurrence an optionally substituted C10-30 alkyl, or a salt thereof.

2. Compound according to claim 1, characterized in that R1 is methyl.

3. Compound according to claim 1, characterized in that R2 is, independently in each occurrence, an optionally substituted C18-26 alkyl, and R3 is, independently in each occurrence, an optionally substituted C18-26 alkyl.

4. Compound according to claim 1, characterized in that each R2 is independently an optionally substituted C22 alkyl and each R3 is independently an optionally substituted C22 alkyl.

5. Compound according to claim 1, characterized in that the compound has the structure of Formula (Ia): Petition 870260086043, 2026 / 08 / 24, p. 335 / 389 2 / 52 or 6. in O a salt thereof. Process for preparation that: men are, (Ia), a compound of Formula (I), independently, an integer from 1 to 5, and (m+n)>3; R1 is a C1-5 alkyl; R2 is, independently in each occurrence, an optionally substituted C10-30 alkyl; R3 is, independently in each occurrence, an optionally substituted C10-30 alkyl, or a salt thereof, said process characterized by comprising: (a) providing a compound of Formula (II) with the structure: Petition 870260086043, 2026 / 08 / 24, p. 336 / 389 3 / 52 (II), where PG is a suitable protecting group; and (b) form the compound of Formula (I) from the compound of Formula (II).

7. Process according to claim 6, characterized in that PG is selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

8. Process according to claim 6, characterized in that the compound of Formula (II) has the structure of Formula (IIa):

9. Process according to claim 6, characterized in that said step (b) of forming the compound of Formula (I) comprises: reacting the compound of Formula (II) with a protecting group removing agent to produce the compound of Formula (I). Petition 870260086043, dated 24 / 08 / 2026, p. 337 / 389 4 / 52 10. Process according to claim 9, characterized in that the protective group removal agent is selected from the group consisting of Pd(PPh)3, PhSiH3, H2, piperidine and trifluoroacetic acid (TFA).

11. Process according to claim 6, characterized in that it further comprises the steps of: providing a compound of Formula (III) with the structure: R1 O wherein PG1 is a suitable protecting group; PG2 is a suitable protecting group; and forming the compound of Formula (II) from the compound of Formula (III) prior to step (a).

12. Process according to claim 11, characterized in that PG1 is independently selected in each occurrence from the group consisting of tert-butyldimethylsilyl (TBS), trimethylsilyl (TMS), triethylsilyl (TES), tert-butyldiphenylsilyl (TBDPS) and triisopropylsilyl (TIPS).

13. Process according to claim 11, characterized in that PG2 is independently selected in each occurrence from the group consisting of tert-butyldimethylsilyl (TBS), trimethylsilyl (TMS), triethylsilyl (TES), tert-butyldiphenylsilyl (TBDPS) and triisopropylsilyl (TIPS).

14. Process, according to claim 11, characterized in that each PG1 and each PG2 are the same.

15. Process, according to claim 11, characterized Petition 870260086043, dated 08 / 24 / 2026, p. 338 / 389 5 / 52 by the fact that PG1 and PG2 are different from each other.

16. Process according to claim 11, characterized in that the compound of Formula (III) has the structure of Formula (IIIa):

17. Process according to claim 11, characterized in that said step of forming the compound of Formula (II) prior to step (a) comprises: reacting the compound of Formula (III) with a protecting group removing agent to obtain a deprotected intermediate; reacting said intermediate with at least one compound of Formula (IV): R-LG (IV), wherein R is an optionally substituted C10-30 alkyl; and LG is a suitable leaving group; to produce the compound of Formula (II).

18. Process according to claim 17, characterized in that LG is selected from a group consisting of halogen, OTf, OMs and OTs.

19. Process according to claim 17, characterized in that the protecting group removal agent is selected from the group consisting of tetrabutylammonium fluoride (TBAF), NH4F, SiF4, AcOH, HCl, LiAlH4 and K2CO3.

20. Process according to claim 11, characterized in that it further comprises the steps of: Petition 870260086043, dated 08 / 24 / 2026, page 339 / 389 6 / 52 providing a compound of Formula (V) with the structure: R1 O forming the compound of Formula (III) from the compound of Formula (V).

21. Process according to claim 20, characterized in that the said step of forming the compound of Formula (III) comprises: reacting the compound of Formula (V) with a compound of Formula (VIa) or Formula (VIb): PG-X (VIa) or PG2O (VIb), wherein X is Cl or Br; to produce the compound of Formula (III).

22. Process according to claim 21, characterized in that the compound of Formula (VIa) or Formula (VIb) is selected from the group consisting of AllocCl, Alloc2O, Cbz2O, CbzCl, FmocCl and Boc2O.

23. Process according to claim 20, characterized in that it further comprises: providing a compound of Formula (VII) with the structure: Petition 870260086043, dated 24 / 08 / 2026, pp. 340 / 389 7 / 52 wherein PG3 is a suitable protecting group; and forming the compound of Formula (V) from the compound of Formula (VII).

24. Process according to claim 23, characterized in that PG3 is selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

25. Process according to claim 23, characterized in that the compound of Formula (VII) has the following structure: OTBS (VIIa) .

26. Process according to claim 23, characterized in that said step of forming the compound of Formula (V) comprises: reacting the compound of Formula (VII) with a protecting group removing agent to produce the compound of Formula (V).

27. Process according to claim 26, characterized in that the protective group removal agent is selected from the group consisting of Pd(PPh)3, PhSiH3, H2, piperidine and trifluoroacetic acid (TFA).

28. Process according to claim 23, characterized in that it further comprises: providing a compound of Formula (VIII) with the structure: Petition 870260086043, dated 24 / 08 / 2026, p. 341 / 389 8 / 52 (O-PG1)m .ΛΛΛΛΛΛ.(O-PG2)n forming the compound of Formula (VII) from the compound of Formula (VIII).

29. Process according to claim 28, characterized in that the said step of forming the compound of Formula (VII) comprises: reacting the compound of Formula (VIII) with a compound of Formula (IX) with the structure: PG3 R1 OO\__ OH R1 O (IX) to produce the compound of Formula (VII).

30. Process according to claim 28, characterized in that the compound of Formula (VIII) has the following structure: TBSO OTBS TBSO OTBS TBSO TBSO (VIIIa).

31. Process according to claim 29, characterized in that the compound of Formula (IX) has the following structure: Fmoc-NH R1O > R1-O (IXa). Petition 870260086043, dated 24 / 08 / 2026, p. 342 / 389 9 / 52 32. Process according to claim 28, characterized in that it further comprises: providing a compound of Formula (X) with the structure: wherein PG4 is a suitable protecting group; and forming the compound of Formula (VIII) from the compound of Formula (X).

33. Process according to claim 32, characterized in that PG4 is selected from the group consisting of allyl, allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

34. Process according to claim 32, characterized in that the compound of Formula (X) has the following structure: (Xa).

35. Process according to claim 32, characterized in that the said step of forming the compound of Formula (VIII) comprises: reacting the compound of Formula (X) with a protecting group removing agent.

36. Process according to claim 35, characterized in that the protective group removal agent is selected from the group consisting of Pd / K2CO3, 3-dimethylbarbituric acid / Pd(PPh3)4, Pd(PPh)3, PhSiH3, H2, piperidine and trifluoroacetic acid (TFA). Petition 870260086043, dated 24 / 08 / 2026, p. 343 / 389 10 / 52 37. Process according to claim 32, characterized in that it further comprises: providing a compound of Formula (XI) with the structure: O (XI); and forming the compound of Formula (X) from the compound of Formula (XI).

38. Process according to claim 37, characterized in that the compound of Formula (XI) has the following structure: OTBS TBSO^Á. TBSO (XIa) .

39. Process according to claim 37, characterized in that the said step of forming the compound of Formula (X) comprises: reacting the compound of Formula (XI) with a compound of Formula (XII): (XII), or a salt thereof, to produce the compound of Formula (X).

40. Process according to claim 37, characterized in that it further comprises: providing a compound of Formula (XIII) with the structure: (O-PG1)m OH (XIII); and forming the compound of Formula (XI) from the compound of Formula (XIII).

41. Process according to claim 40, characterized in that the compound of Formula (XIII) has the following structure: Petition 870260086043, dated 08 / 24 / 2026, p. 344 / 389 11 / 52 OTBS TBSCkX là ΌH TBSO (Xllla) .

42. Process according to claim 40, characterized in that the said step of forming the compound of Formula (XI) comprises: reacting the compound of Formula (XIII) with an oxidizing agent to produce the compound of Formula (XI).

43. Process according to claim 42, characterized in that the oxidizing agent is selected from the group consisting of pyridinium chlorochromate (PCC), pyridinium dichromate (PDC), silver carbonate (Ag2CO3), tetra-n-propylammonium perruthenate (TPAP) and Dess-Martin periodinane (DMP).

44. Process according to claim 40, characterized in that it further comprises: providing a compound of Formula (XIV) with the structure: (O-PG1)m O (XIV), wherein Y is -OC1-6 alkyl; and forming the compound of Formula (XIII) from the compound of Formula (XIV).

45. Process according to claim 44, characterized in that the compound of Formula (XIV) has the following structure: OTBS TBSO^Y, TBSO Y 0\ (XIVa) .

46. ​​Process according to claim 44, characterized in that the said step of forming the compound of Formula (XIII) comprises: Petition 870260086043, dated 24 / 08 / 2026, p. 345 / 389 12 / 52 reacting the compound of Formula (XIV) with a reducing agent.

47. Process according to claim 46, characterized in that the reducing agent is selected from the group consisting of LiAlH4, DIBALH and LiBH4.

48. Process according to claim 44, characterized in that it further comprises: providing a compound of Formula (XV) with the structure: (OH)m (XV); and forming the compound of Formula (XIV) from the compound of Formula (XV).

49. Process according to claim 48, characterized in that the compound of Formula (XV) has the following structure: OH HO HO °\ (XVa) .

50. Process according to claim 48, characterized in that the said step of forming the compound of Formula (XIV) comprises: reacting the compound of Formula (XV) with a protecting group introducing agent to produce the compound of Formula (XIV).

51. Process according to claim 50, characterized in that the protective group introducing agent is selected from the group consisting of TBSCl, TBSOTf, TMSCl, TMSOTf, TESCl, TESOTf, TBDPSCl, TBDPSOTf, TIPSCl and TIPSOTf.

52. Product characterized by being prepared by the method as defined in any one of claims 6 to 51.

53. Product according to claim 52, characterized in that the product is a compound of Formula (I): Petition 870260086043, dated 24 / 08 / 2026, page 346 / 389 13 / 52 wherein: men are independently an integer from 1 to 5, and (m+n)>3; R1 is a C1-5 alkyl; R2 is independently in each occurrence an optionally substituted C10-30 alkyl; and R3 is independently in each occurrence an optionally substituted C10-30 alkyl, or a salt thereof.

54. Product according to claim 53, characterized in that the product is a compound of Formula (Ia): (Ia), or a salt thereof.

55. Method of using a compound of Formula (I): Petition 870260086043, dated 24 / 08 / 2026, page 347 / 389 14 / 52 wherein: men are independently an integer from 1 to 5, and (m+n)>3; R1 is a C1-5 alkyl; R2 is independently in each occurrence an optionally substituted C10-30 alkyl; and R3 is independently in each occurrence an optionally substituted C10-30 alkyl, or a salt thereof, characterized in that it is for producing a peptide or a peptidomimetic.

56. Method according to claim 55, characterized in that the compound of Formula (I) is used as a carrier to produce a peptide or a peptidomimetic.

57. Method according to claim 55, characterized in that the peptidomimetic is a compound of Formula: a salt thereof.

58. Method according to claim 55, characterized in that the peptidomimetic is a compound of Formula: Petition 870260086043, dated 08 / 24 / 2026, pp. 348 / 389 15 / 52 or a salt thereof.

59. Compound characterized by being manufactured using a compound of Formula (I): wherein: men are independently an integer from 1 to 5, and (m+n)>3; R1 is C1-5 alkyl; R2 is independently selected in each occurrence of an optionally substituted C10-30 alkyl; and R3 is independently selected in each occurrence of an optionally substituted C10-30 alkyl, or a salt thereof.

60. Compound, according to claim 59, characterized in that the compound has a formula: Petition 870260086043, dated 08 / 24 / 2026, page 349 / 389 16 / 52 a salt thereof.

61. Compound according to claim 59, characterized in that the compound has the following formula: a salt thereof.

62. Pharmaceutical composition characterized in that it comprises the peptidomimetic as defined in claim 57 or the compound as defined in claim 59 or 60.

63. Pharmaceutical dosage form characterized in that it comprises the peptidomimetic as defined in claim 57 or the compound as defined in claim 59 or 60.

64. Method for selectively targeting GLP1R onto a cell surface characterized in that it is with the peptidomimetic as defined in claim 57 or the compound as defined in claim 59 or 60.

65. Method according to claim 64, characterized in that the cell is a mammalian cell.

66. Method according to claim 64 or 65, characterized in that the cell is a human cell.

67. Method for increasing GLP1R activity in an individual who needs it, characterized in that it comprises administering to the individual an effective amount of the peptidomimetic as defined in claim 57 or of the compound as defined in claim 59 or 60, of the composition as defined in claim 62 or of the dosage form as defined in claim 63.

68. A method for reducing blood glucose levels in an individual who needs it, characterized in that it comprises administering to the individual an effective amount of the peptidomimetic as defined in claim 57 or of the compound as defined in claim 59 or 60, of the composition as defined in claim 62 or of the dosage form as defined in claim 63.

69. A method for reducing body weight in an individual who needs it, characterized in that it comprises administering to the individual an effective amount of the peptidomimetic as defined in claim 57 or of the compound as defined in claim 59 or 60, of the composition as defined in claim 62 or of the dosage form as defined in claim 63.

70. Method for treating a condition associated with GLP1R in an individual who needs it, characterized in that it comprises administering to the individual an effective amount of the peptidomimetic as defined in claim 57 or of the compound as defined in claim 59 or 60, of the composition as defined in claim 62 or of the dosage form as defined in claim 63.

71. Method, according to claim 70, characterized in that the condition associated with GLP1R is type II diabetes, obesity, liver disease, coronary artery disease, or kidney disease.

72. Method, according to claim 70, characterized in that the condition associated with GLP1R is type II diabetes and / or obesity.

73. Method, according to any one of claims 67 to 72, characterized in that the peptidomimetic as defined in claim 57 or the compound as defined in claim 59 or 60, the composition as defined in claim 62 or the dosage form as defined in claim 63 is administered subcutaneously, intravenously, intradermally, intraperitoneally or intramuscularly.

74. Method for producing a peptide or a peptidomimetic, the method characterized in that it comprises the steps of: (a) providing a compound of Formula (I): wherein: men are independently an integer from 1 to 5, and (m+n)>3; R1 is C1-5 alkyl; R2 is independently selected at each occurrence of an optionally substituted C10-30 alkyl; and R3 is independently selected at each occurrence of an optionally substituted C10-30 alkyl, or a salt thereof; (b) providing a first amino acid (AA1); and (c) coupling the first amino acid (AA1) to the compound of Formula (I) to form a peptide bond between the first amino acid (AA1) and the compound of Formula (I).

75. Method, according to claim 74, characterized by the fact that the first amino acid (AA1) contains a protected amino group.

76. Method, according to claim 74, characterized by the fact that the first amino acid (AA1) is I.

77. Method according to claim 74, characterized in that it further comprises the step of: activating the chemical groups on the first amino acid (AA1) to prepare the first amino acid (AA1) for coupling with the compound of Formula (I) before step (c).

78. Method according to claim 74, characterized in that it further comprises the steps of: (d) removing the protecting group from the first amino acid (AA1); (e) providing a second amino acid (AA2); and (f) coupling the second amino acid (AA2) to the first amino acid (I-AA1) to form a peptide bond between the second amino acid (AA2) and the first amino acid (I-AA1-AA2).

79. Method according to claim 78, characterized in that the second amino acid (AA2) is O 80. Method according to claim 78, characterized in that it further comprises the steps of: (g) removing the protecting group from the second amino acid (AA2); (h) providing a third amino acid (AA3); and (i) coupling the third amino acid (AA3) to the second amino acid to form a peptide bond between the third amino acid (AA3) and the second amino acid (I-AA1-AA2-AA3).

81. Method according to claim 80, characterized by the fact that the third amino acid (AA3) is 82. Method according to claim 80, characterized in that it further comprises the steps of: (j) removing the protecting group from the third amino acid (AA3); (k) providing a fourth amino acid (AA4); and (l) coupling the fourth amino acid (AA4) to the third amino acid to form a peptide bond between the fourth amino acid (AA4) and the third amino acid (I-AA1-AA2-AA3-AA4).

83. Method according to claim 82, characterized in that the fourth amino acid (AA4) is NHFmoc or NHFmoc 84. Method according to claim 82, characterized in that it further comprises: (m) removing the protecting group from the fourth amino acid (AA4); (n) providing a fifth amino acid (AA5); and (o) coupling the fifth amino acid (AA5) to the fourth amino acid to form a peptide bond between the fifth amino acid (AA5) and the fourth amino acid (I-AA1-AA2-AA3-AA4-AA5).

85. Method according to claim 84, characterized in that the fifth amino acid (AA5) is NHFmoc or 1 NHFmoc.

86. Method according to claim 84, characterized in that it further comprises: (p) removing the protecting group from the fifth amino acid (AA5); (q) providing a sixth amino acid (AA6); and Petition 870260086043, dated 24 / 08 / 2026, p. 354 / 389 21 / 52 (r) coupling the sixth amino acid (AA6) to the fifth amino acid to form a peptide bond between the sixth amino acid (AA6) and the fifth amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6).

87. Method, according to claim 86, characterized by the OOwmoc in that the sixth amino acid (AA6) is F.

88. Method according to claim 86, characterized in that it further comprises: (s) removing the protecting group from the sixth amino acid (AA6); (t) providing a seventh amino acid (AA7); and (u) coupling the seventh amino acid (AA6) to the sixth amino acid to form a peptide bond between the seventh amino acid (AA7) and the sixth amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6-AA7).

89. Method according to claim 88, characterized by the fact that the seventh amino acid (AA7) is NHFmoc or 90. Method according to claim 88, characterized in that it further comprises: (v) removing the protecting group from the seventh amino acid (AA7); (w) providing an eighth amino acid (AA8); and (x) coupling the eighth amino acid (AA8) to the seventh amino acid to form a peptide bond between the eighth amino acid (AA8) and the seventh amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6-AA7-AA8).

91. Method according to claim 90, characterized by the fact that the eighth amino acid (AA8) is θH.

92. Method according to claim 90, characterized in that it further comprises: (y) removing the protecting group from the eighth amino acid (AA8); Petition 870260086043, dated 24 / 08 / 2026, page 355 / 389 22 / 52 (z) providing a ninth amino acid (AA9); and (aa) coupling the ninth amino acid (AA9) to the eighth amino acid to form a peptide bond between the ninth amino acid (AA9) and the eighth amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6-AA7-AA8-AA9).

93. Method by which nN NHFmoc according to claim 92, characterized OH that the ninth amino acid (AA9) is nn NHFmoc or 94. Method according to claim 92, characterized in that it further comprises: (bb) removing the protecting group from the ninth amino acid (AA9); (cc) providing a tenth amino acid (AA10); and (dd) coupling the tenth amino acid (AA10) to the ninth amino acid to form a peptide bond between the tenth amino acid (AA10) and the ninth amino acid (I-AA1-AA2-AA3-AA4-AA5-AA6-AA7—AA8AA9-AA10).

95. Method, according to claim 94, characterized by the fact that the tenth amino acid (AA10) is H / x .

96. Method according to claim 94, characterized in that it further comprises: repeating the steps of (i) removing the protecting group from the amino acid (AAn); (ii) providing a successor amino acid (AAn+i); and (iii) coupling the successor amino acid (AAn+i) to the amino acid (AAn) to form a peptide bond between the successor amino acid (AAn+i) and the amino acid (AAn), wherein said repetition is performed i00 times.

97. Method according to claim 94, characterized in that it further comprises: Petition 870260086043, dated 24 / 08 / 2026, p. 356 / 389 23 / 52 (ee) removing the protecting group from the tenth amino acid (AA10); (ff) providing a compound of Formula (B): BocHN where x is an integer from 1 to 15; and (gg) coupling the compound of Formula (B) to one of the amino acids in the peptide or peptidomimetic to form a triazole ring.

98. Method according to claim 97, characterized in that the compound of Formula (B) has the following Formula: BocHN 99. Method, according to any one of claims 74 to 98, characterized in that it further comprises: (hh) cleaving the peptide bond between the first amino acid (AA1) and the compound of Formula (I) to obtain the peptide or peptidomimetic.

100. Method, according to any one of claims 74 to 98, characterized in that each of the first amino acid (AA1), the second amino acid (AA2), the third amino acid (AA3), the fourth amino acid (AA4), the fifth amino acid (AA5), the sixth amino acid (AA6), the seventh amino acid (AA7), the eighth amino acid (AA8), the ninth amino acid (AA9), the tenth amino acid (AA10) and the successor amino acid (AAn+i) are selected independently from the group consisting of Petition 870260086043, dated 24 / 08 / 2026, page 357 / 389 24 / 52 O O NH-PGb PG5 where PG5 is a suitable protecting group.

101. Method according to claim 100, characterized in that PG5 is independently selected in each occurrence of the group consisting of triphenylmethyl (Trt), allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

102. Method, according to any one of claims 74 to 98, characterized in that each of the first amino acid (AA1), second amino acid (AA2), third amino acid (AA3), fourth amino acid (AA4), fifth amino acid (AA5), sixth amino acid (AA6), seventh amino acid (AA7), eighth amino acid (AA8), ninth amino acid (AA9), tenth amino acid (AA10) and the successor amino acid (AAn+1) are selected independently of the group comprising Petition 870260086043, dated 24 / 08 / 2026, pp. 358 / 389 25 / 52 NHFmoc 103. Method according to claim 99, characterized in that the peptidomimetic has a formula: a salt thereof.

104. Method, according to claim 99, characterized in that the peptidomimetic has a Formula: Petition 870260086043, dated 08 / 24 / 2026, p. 359 / 389 26 / 52 or a salt thereof.

105. Compound characterized by having a structure of Formula (AI): (AI), wherein: men are independently an integer from 0 to 5; R1a is C1-5 alkyl; R2a is independently in each occurrence an optionally substituted C10-30 alkyl; and R3a is independently in each occurrence an optionally substituted C10-30 alkyl, or a salt thereof.

106. Compound according to claim 105, characterized in that R1a is methyl.

107. Compound according to claim 105, characterized in that R2a is, independently in each occurrence, an optionally substituted C18-26 alkyl and R3a is, independently in each occurrence, an optionally substituted C18-26 alkyl.

108. Compound according to claim 105, characterized in that each R2a is independently an optionally substituted C22 alkyl and each R3a is independently an optionally substituted C22 alkyl.

109. Compound characterized by having a structure of Formula (BI): wherein: (BI), m is an integer from 1 to 5; R1b is C1-5 alkyl; and R2b is, independently in each occurrence, an optionally substituted C10-30 alkyl; or a salt thereof.

110. Compound according to claim 109, characterized in that R1b is methyl.

111. Compound according to claim 109, characterized in that each R2b is independently an optionally substituted C18-26 alkyl.

112. Compound according to claim 109, characterized in that each R2b is independently an optionally substituted C22 alkyl.

113. Compound characterized by having a structure of Formula (CI): wherein: (CI), men are independently an integer from 1 to 5, and (m+n)>3; Petition 870260086043, dated 24 / 08 / 2026, p. 361 / 389 28 / 52 R2c is, independently in each occurrence, an optionally substituted C10-30 alkyl; and R3c is, independently in each occurrence, an optionally substituted C10-30 alkyl, or a salt thereof.

114. Compound according to claim 113, characterized in that R2c is, independently in each occurrence, an optionally substituted C18-26 alkyl and R3c is, independently in each occurrence, an optionally substituted C18-26 alkyl.

115. Compound according to claim 113, characterized in that each R2c is independently an optionally substituted C22 alkyl and each R3c is independently an optionally substituted C22 alkyl.

116. Process for preparing a compound of Formula (DI): where: k is an integer from 1 to 15; q is an integer from 0 to 10; R1d is C1-6 alkyl; PG6 is a suitable protecting group; and PG7 is a suitable protecting group, or a salt thereof, said process characterized by comprising: (a) providing a compound of Formula (DII) with the structure: Petition 870260086043, dated 24 / 08 / 2026, p. 362 / 389 29 / 52 (b) forming the compound of Formula (DI) from the compound of Formula (DII).

117. Process according to claim 116, characterized in that PG6 is selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

118. Process according to claim 116, characterized in that PG7 is selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

119. Process according to claim 116, characterized in that the compound of Formula (DI) has the structure of Formula (DIa) or Formula (DIb):

120. Process according to claim 116, characterized in that the compound of Formula (DII) has the structure of Formula (DIIa) or Formula (DIIb): Petition 870260086043, dated 24 / 08 / 2026, p. 363 / 389 30 / 52 claim 116, characterized in that said step (b) of forming the compound of Formula (DI) comprises: reacting the compound of Formula (DII) with a compound of Formula (DIII): PG7 k (DIII), to produce the compound of Formula (II).

122. Process according to claim 121, characterized in that the compound of Formula (DIII) has the structure of Formula (DIIIa): the (DIIIa).

123. Process according to claim 116, characterized in that it further comprises the steps of: providing a compound of Formula (DIV) with the structure: Petition 870260086043, 2026 / 08 / 24, p. 364 / 389 31 / 52 O H2N,, < OH N3x7 1 X R1 dq (DIV) or a salt thereof; and forming the compound of Formula (DII) from the compound of Formula (DIV) prior to step (a).

124. Process according to claim 123, characterized in that the compound of Formula (DIV) has the structure of Formula (DIVa) or Formula (DIVb): claim 123, characterized in that said step of forming the compound of Formula (DII) comprises: reacting the compound of Formula (DIV) with a compound of Formula (DVa) or Formula (DVb): PG6-X (DVa) or PG62O (DVb), where X is OSu, OTf, Cl or Br; to produce the compound of 126. Process, in accordance with claim 125, the compound of Formula (DVa) or Petition 870260086043, of 08 / 24 / 2026, page 365 / 389 32 / 52 Formula (DVb) is selected from the group consisting of AllocCl, Al110C2O, Cbz2O, CbzCl, FmocCl, FmocOSu and Boc2O.

127. Process according to claim 123, characterized in that it further comprises the steps of: providing a compound of Formula (DVI) with the structure: wherein PG8 is a suitable protecting group; and forming the compound of Formula (DIV) from the compound of Formula (DVI).

128. Process according to claim 127, characterized in that said step of forming the compound of Formula (DIV) comprises: reacting the compound of Formula (DVI) with a protecting group removing agent to produce the compound of Formula (DIV).

129. Process according to claim 128, characterized in that the protective group removal agent is selected from the group consisting of Pd(PPh)3, PhSiH3, H2, piperidine and trifluoroacetic acid (TFA).

130. Process according to claim 127, characterized in that the compound of Formula (DVI) has the structure of Formula (DVIa) or Formula (DVIb): Petition 870260086043, dated 24 / 08 / 2026, p. 366 / 389 33 / 52 claim 127, characterized in that it further comprises the steps of: providing a compound of Formula (DVII) with the structure: and from the compound of Formula (DVII).

132. Process according to claim 131, characterized in that the said step of forming the compound of Formula (DVI) comprises: reacting the compound of Formula (DVII) with a base to produce the compound of Formula (DVI).

133. Process according to claim 128, characterized in that the base is selected from the group consisting of LiOH, NaOH and KOH.

134. Process according to claim 131, characterized in that the compound of Formula (DVII) has the structure of Formula (DVIIa) or Formula (DVIIb):

135. Process according to claim 131, characterized in that it further comprises the steps of: providing a compound of Formula (DVIII) with the structure: wherein LG' is a suitable life group; and forming the compound of Formula (DVII) from the compound of Formula (DVIII).

136. Process according to claim 135, characterized in that the said step of forming the compound of Formula (DVII) comprises: reacting the compound of Formula (DVIII) with an azide group introducing agent to produce the compound of Formula (DVII).

137. Process, according to claim 136, Petition 870260086043, dated 24 / 08 / 2026, pp. 368 / 389 35 / 52 characterized in that the azide group introducing agent is selected from the group consisting of NaN3, TMSN3, (PhO)2P(O)N3, Zn(N3)2*2Py and n-Bu4NN3.

138. Process, according to claim 135, characterized in that LG' is selected from the group consisting of halogen, OTf, OMs and OTs.

139. Process according to claim 135, characterized in that the compound of Formula (DVIII) has the structure of Formula (DVIIIa) or Formula (DVIIIb):

140. Process according to claim 135, characterized in that it further comprises the steps of: providing a compound of Formula (DIX) with the structure: LG LGt J^X Jx Jx R (DIX), wherein LG'' is a suitable life group; and forming the compound of Formula (DVIII) from the compound of Formula (DIX).

141. Process, according to claim 140, characterized in that the LG'' is selected from the group that Petition 870260086043, of 08 / 24 / 2026, pp. 369 / 389 36 / 52 consists of halogen, OTf, OMs and OTs.

142. Process according to claim 140, characterized in that the said step of forming the compound of Formula (DVIII) comprises: reacting the compound of Formula (DIX) with a compound of Formula (DX): PG8 HN,, OMe (DX) to produce the compound of Formula (DVII).

143. Process according to claim 140, characterized in that the compound of Formula (DIX) has the structure of Formula (DIXa): (DIXa).

144. Process according to claim 142, characterized in that the compound of Formula (DX) has the structure of Formula (Dxa): । II HN,, A < OMe (DXa).

145. Process according to claim 140, characterized in that it further comprises the steps of: providing a compound of Formula (DXI) with the structure: Petition 870260086043, dated 24 / 08 / 2026, pp. 370 / 389 37 / 52 wherein (DXI), R2d is C1-6 alkylene; and forming the compound of Formula (DIX) from the compound of Formula (DXI).

146. Process according to claim 145, characterized in that the said step of forming the compound of Formula (DIX) comprises: reacting the compound of Formula (DXI) with a reducing agent to produce the compound of Formula (DIX).

147. Process according to claim 145, characterized in that the reducing agent is selected from the group consisting of H2, NH4HCO2, NABH(Oac)3 and LiAlH4.

148. Process, according to claim 141, characterized in that the compound of Formula (DXI) has the structure of Formula (DXIa): 0 (DXIa).

149. Process according to claim 145, characterized in that it further comprises the steps of: providing a compound of Formula (DXII) with the structure: LG o (DXII), and forming the compound of Formula (DXI) from the compound of Formula (DXII).

150. Process according to claim 149, characterized in that the said step of forming the compound of Formula (DXI) comprises: Petition 870260086043, dated 24 / 08 / 2026, p. 371 / 389 38 / 52 reacting the compound of Formula (DXII) with a compound of Formula (DXIII): PPh3*C1-6alkyl-Hal (DXIII), wherein Hal is halogen, to produce the compound of Formula (DXI).

151. Process according to claim 149, characterized in that the compound of Formula (DXII) has the structure of Formula (DXIIa): O (DXIIa).

152. Process according to claim 150, characterized in that the compound of Formula (DXIII) has the structure of Formula (DXIIIa): PPh3*MeBr (DXIIIa).

153. Process according to claim 149, characterized in that it further comprises the steps of: providing a compound of Formula (DXIV) with the structure: O (DXIV), and forming the compound of Formula (DXII) from the compound of Formula (DXIV).

154. Process according to claim 153, characterized in that said step of forming the compound of Formula (DXII) comprises: reacting the compound of Formula (DXIV) with a compound of Formula (DXV): LGt 'A^lg' (DXV), wherein Petition 870260086043, dated 24 / 08 / 2026, p. 372 / 389 39 / 52 LG”' is a suitable co-existence group, to produce the compound of Formula (DXII).

155. Process according to claim 154, characterized in that the LG is selected from the group consisting of halogen, OTf, OMs and OTs.

156. Process according to claim 153, characterized in that the compound of Formula (DXIV) has the structure of Formula (DXIVa): O (DXIVa).

157. Process according to claim 142, characterized in that it further comprises the steps of: providing a compound of Formula (DXVI) with the structure: (DXVI) wherein LG* is a suitable coexisting group, forming the compound of Formula (DX) from the compound of Formula (DXVI).

158. Process according to claim 157, characterized in that LG* is selected from the group consisting of halogen, OTf, OMs and OTs.

159. Process according to claim 157, characterized in that the said step of forming the compound of Formula (DX) comprises: reacting the compound of Formula (DXVI) with a compound of Formula (DXVII): Petition 870260086043, dated 24 / 08 / 2026, page 373 / 389 40 / 52 θ \ / -χ ι Vo I (DXVII), to produce the compound of Formula (DX).

160. Process according to claim 157, characterized in that the compound of Formula (DXVI) has the structure of Formula (DXVIc): Boc O HN,, ·< OMe u OTf (DXVIc).

161. Process according to claim 157, characterized in that it further comprises the steps of: providing a compound of Formula (DXVIII) with the structure: PG6 O HN,, Jk ·< OMe A OH (DXVIII), and forming the compound of Formula (DXVI) from the compound of Formula (DXVIII).

162. Process according to claim 161, characterized in that the said step of forming the compound of Formula (DXVI) comprises: reacting the compound of Formula (DXVIII) with a compound of Formula (DXIXa) or Formula (DXIXb): LG*-X (DXIXa) or LG*2O (DXIXb), wherein X is OSu, Cl or Br; to produce the compound of Formula (DXVI). Petition 870260086043, dated 24 / 08 / 2026, pp. 374 / 389 41 / 52 163. Process according to claim 162, characterized in that the compound of Formula (DXIXa) or Formula (DXIXb) is selected from the group consisting of TfCl, Tf2O, MsCl and Ms2O.

164. Process for preparing a compound of Formula (DII): where: q is an integer from 0 to 10; R1d is C1-6 alkyl; and PG6 is a suitable protecting group, or a salt thereof, said process characterized by comprising: (a) providing a compound of Formula (DXXI) with the structure: (DXXI) or a salt thereof, (b) forming the compound of Formula (DII) from the compound of Formula (DXXI).

165. Process according to claim 164, characterized in that PG6 is selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

166. Process according to claim 164, characterized in that the compound of Formula (DXXI) is treated with compound O OH NHFmoc. Petition 870260086043, dated 08 / 24 / 2026, pp. 375 / 389 42 / 52 167. Process according to claim 164, characterized in that the compound of Formula (DXXI) is treated with a catalyst.

168. Process according to claim 167, characterized in that the catalyst is Pd(dppf)Cl2-DCM.

169. Process according to claim 164, characterized in that the compound of Formula (DXXI) is treated with a base.

170. Process according to claim 169, characterized in that the base is K2CO3.

171. Process according to claim 164, characterized in that the preparation is carried out in a solvent mixture composed of H2O / iPrOH.

172. Process, according to claim 164, characterized in that the compound of Formula (DII) has the structure of Formula (DIIa) or Formula (DIIb): claim 164, characterized in that the compound of Formula (DXXI) is formed by the exposure 174. Process, according to which it is characterized by the fact that it is formed in the presence of PPh3.

175. Process, in accordance with the fact that it was formed in the presence of DIAD.

176. Process, according to which, characterized by the fact that formed in the presence of sieves with claim 173, the compound of Formula (DXXI) is with claim 173, the compound of Formula (DXXI) is with claim 173, the compound of Formula (DXXI) is molecular of 4Â.

177. Process, according to claim 173, characterized by the fact that the compound of Formula (DXXI) is formed in an organic solvent.

178. Process, according to which the 179. Process, according to claim 177, organic solvent is THF. with claim 173, characterized in that exposure to PBin 2. formed by 180. Process according to claim 179, characterized in that it is formed in the presence of Pd(OAc)2.

181. Process, according to claim 179, Petition 870260086043, dated 08 / 24 / 2026, pp. 377 / 389 44 / 52 characterized by the fact that HO O i B- Rld is formed in the presence of PCya.

182. Process according to claim 179 characterized in that HO O i B- Rld is formed in the presence of KOAc.

183. Process according to claim 179 characterized in that HO O^ I B'O Rld is formed in the presence of dioxane.

184. Process according to claim 179 characterized in that HO O^ i BO Rld is formed at an elevated temperature for a period of time.

185. Process according to claim 179 characterized in that HO Br Rld is formed by exposing HO R1d to Bu4N+BR3-.

186. Process according to claim 185 characterized in that HO Br R1d is formed in an organic solvent.

187. Process according to claim 186 Petition 870260086043, dated 08 / 24 / 2026, pp. 378 / 389 45 / 52 characterized in that the organic solvent is a mixture of DCM and methanol.

188. Process for preparing a compound of Formula (DII): wherein: q is an integer from 0 to 10; R1d is C1-6 alkyl; and PG6 is a suitable protecting group, or a salt thereof, said process characterized by comprising: (a) providing a compound of Formula (DIV) with the structure: (DIV) or a salt thereof, (b) forming the compound of Formula (DII) from the compound of Formula (DIV).

189. Process according to claim 188, characterized in that PG6 is selected from the group consisting of allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc).

190. Process according to claim 188, characterized in that the compound of Formula (DII) has the structure of Formula (DIIa) or Formula (DIIb): Petition 870260086043, dated 24 / 08 / 2026, pp. 379 / 389 46 / 52 188, characterized in that the compound of Formula (DIV) has the structure of Formula (DIVa) or Formula (DIVb):

192. Process according to claim 188, characterized in that said step of forming the compound of Formula (DII) comprises: reacting the compound of Formula (DIV) with a compound of Formula (DVa) or Formula (DVb): PG6-X (DVa) or PG62O (DVb), wherein X is OSu, Otf, Cl or Br; to produce the compound of Formula (DII).

193. Process according to claim 192, characterized in that the compound of Formula (DVa) or Formula (DVb) is selected from the group consisting of AllocCl, Alloc2O, Cbz2O, CbzCl, FmocCl, FmocOSu and Boc2O.

194. Process according to claim 188, characterized in that it further comprises the steps of: providing PG8 as a suitable protecting group; and forming the compound of Formula (DIV) from the compound of Formula (DXVI).

195. Process according to claim 194, characterized in that the said step of forming the compound of Formula (DIV) comprises: reacting the compound of Formula (DXVI) with a protecting group removing agent to produce the compound of Formula (DIV).

196. Process according to claim 195, characterized in that the protecting group removal agent is selected from the group consisting of HCl, Pd(PPh)3, PhSiH3, H2, piperidine and trifluoroacetic acid (TFA).

197. Process according to claim 194, characterized in that the compound of Formula (DXVI) has the structure of Formula (DXVIa) or Formula (DXVIb): Petition 870260086043, dated 24 / 08 / 2026, pp. 381 / 389 48 / 52 198. Process according to claim 194, characterized in that it further comprises the steps of: providing a compound of Formula (DXVII) with the structure: wherein LG' is a suitable life group; and forming the compound of Formula (DXVI) from the compound of Formula (DXVII).

199. Process according to claim 198, characterized in that the said step of forming the compound of Formula (DXVI) comprises: reacting the compound of Formula (DXVII) with an azide group introducing agent to produce the compound of Formula (DXVI).

200. Process, according to claim 199, characterized in that the introducing agent of the group Petition 870260086043, dated 08 / 24 / 2026, pp. 382 / 389 49 / 52 azido is selected from the group consisting of NaNa, TMSN3, (PhO)2P(O)N3, Zn(Na)2*2Py and n-BuaNNa.

201. Process, according to claim 198, characterized in that LG' is selected from the group consisting of halogen, OTf, OMs and OTs.

202. Process according to claim 198, characterized in that the compound of Formula (DXVII) has the structure of Formula (DXVIIa) or Formula (DXVIIb):

203. Process, according to claim 198, characterized in that it further comprises the steps of: providing a compound of Formula (DIX) with the structure: wherein (DIX), LG'' is a suitable life group; and forming the compound of Formula Formula (DIX).

204. Process, characterized in that it consists of halogen, OTf, OMs (DXVII) from the compound of claim 203, LG'' is selected from the group that and OTs. Petition 870260086043, dated 24 / 08 / 2026, pp. 383 / 389 50 / 52 205. Process according to claim 203, characterized in that the said step of forming the compound of Formula (DXVII) comprises: reacting the compound of Formula (DIX) with a compound of Formula (DXVIII): PG8 HN,, ν,ΧT1 -—Λ 1 Y-° to produce the compound of 206. Process, according to which the structure of Formula (DIXa): 0 OC1-6 alkyl (DXVIII) Formula (DXVII) has the structure of Formula (DIXa): 0 OC1-6 alkyl (DXVIII) Formula (DXVII). with claim 203, the compound of Formula (DIX) has 207. Process, characterized by having the structure of zX / Br θ (DIXa). according to claim 205, the fact that the compound of Formula (DXVIII) Formula (DXVIIIa): V°'B Vo 208. Process, characterized by the fact that the steps of: providing a compound HN,, Y Ot-Bu XX (DXVIIIa), according to claim 203, which further comprises the steps of Formula (DXIX) with the structure: Petition 870260086043, dated 24 / 08 / 2026, pp. 384 / 389 51 / 52 HO LG' Rld (DXIX), and forming the compound of Formula (DIX) from the compound of Formula (DXIX).

209. Process according to claim 208, characterized in that said step of forming the compound of Formula (DIX) comprises: reacting the compound of Formula (DXIX) with a compound of Formula (DXV): (DXV), wherein LG' is a suitable co-existing group, to produce the compound of Formula (DXIX).

210. Process, according to claim 209, characterized in that LG' is selected from the group consisting of halogen, OTf, OMs and OTs.

211. Process according to claim 208, characterized in that the compound of Formula (DXIX) has the structure of Formula (DXIXa): Br (DXIXa).

212. Process according to claim 209, characterized in that the compound of Formula (DXV) has the structure of Formula (DXVa): (DXVa) 213. Process, according to claim 208, characterized in that it further comprises the steps of: providing a compound of Formula (DXX) with the structure: Petition 870260086043, dated 08 / 24 / 2026, pp. 385 / 389 52 / 52 HO R1d (DXX), and forming the compound of Formula (DXIX) from the compound of Formula (DXX).

214. Process according to claim 213, characterized in that said step of forming the compound of Formula (DXIX) comprises: reacting the compound of Formula (DXX) with an introducing agent LG” to produce the compound of Formula (DXIX).

215. Process, according to claim 214, characterized in that the introducing agent LG” is NBu4Bra.

216. Process according to claim 213, characterized in that the compound of Formula (DXX) has the structure of Formula (DXXa): (DXXa) Petition 870260086043, dated 08 / 24 / 2026, p. 386 / 389 1 / 45 Figure 1 Petition 870250075820, dated 08 / 27 / 2025, p. 393 / 438 2 / 45 Figure 1 (cont.) Tag5-10AA Petition 870250075820, dated 08 / 27 / 2025, p. 394 / 438 3 / 45 co Petition 870250075820, dated 08 / 27 / 2025, p. 395 / 438 4 / 45 Figure 2 Tag1-2AA Tag1-3AA Petition 870250075820, dated 08 / 27 / 2025, p. 396 / 438 5 / 45 Figure 2 (cont.) Petition 870250075820, dated 08 / 27 / 2025, p. 397 / 438 6 / 45 Figure 2 (cont.) Petition 870250075820, dated 08 / 27 / 2025, p. 398 / 438 7 / 45 Figure 3 Petition 870250075820, dated 08 / 27 / 2025, p. 399 / 438 8 / 45 Figure 3 (cont.) Tag2-6AA Petition 870250075820, dated 08 / 27 / 2025, p. 400 / 438 9 / 45 Figure 3 (cont.) Petition 870250075820, dated 08 / 27 / 2025, p. 401 / 438 10 / 45 Figure 4 Tag3-1AA Petition 870250075820, dated 08 / 27 / 2025, p. 402 / 438 11 / 45 Figure 4 (cont.) N-Fmoc-Tag3-3AA Tag3-3AA Petition 870250075820, dated 08 / 27 / 2025, page 403 / 438 12 / 45 Figure 4 (cont.) Tag3-4AA Petition 870250075820, dated 08 / 27 / 2025, page 404 / 438 13 / 45 N-Fmoc-Tag3-5AA Reagents and conditions: f) AA1 (1.5 eq.), DIC (1.5 eq.), HOAt (1.5 eq.), DCM (2 mL), 20 °C, 12 h, 78%; g) 20% piperidine in THF, 20 °C, 2 h, 95%; h) AA2 (1.5 eq.), DIC (1.5 eq.), HOAt (1.5 eq.), DCM (2 mL), 20 °C, 12 h, 63%; i) 20% piperidine in THF, 20 °C, 2 h, 97%; j) AA3 (1.5 eq.), DIC (1.5 eq.), HOAt (1.5 eq.), DCM (4 mL), 20 °C, 12 h, 74%; k) 20% piperidine in THF, 20 °C, 2 h, 89%; 1) AA4 (1.5 eq.), DIC (1.5 eq.), HOAt (1.5 eq.), DCM (4 mL), 20 °C, 12 h, 89%; m) 20% piperidine in THF, 20 °C, 2 h, 91%; n) AA5 (1.5 eq.), DIC (1.5 eq.), HOAt (1.5 eq.), DCM (4 mL), 20 °C, 12 h, 90%. Figure 4 (cont.) Petition 870250075820, dated 08 / 27 / 2025, p. 405 / 438 14 / 45 Figure 5 Petition 870250075820, dated 08 / 27 / 2025, p. 406 / 438 15 / 45 Figure 5 (cont.) Tag4-6AA Tag4-7AA Petition 870250075820, dated 08 / 27 / 2025, p.407 / 438 16 / 45 Figura 5 (cont.) Tag4-9AA Petição 870250075820, de 27 / 08 / 2025, pág. 408 / 438 17 / 45 Reagentes e condições: 1) AA1 (1,5 eq.), DIC (1,5 eq.), HOAt (1,5 eq.), DCM (2 mL), 20 °C, 12 h; 20% de piperidina em THF, 20 °C, 2 h; 2) AA2 (1,5 eq.), DIC (1,5 eq.), HOAt (1,5 eq.), DCM (2 mL), 20 °C, 12 h; 20% de piperidina em THF, 20 °C, 2 h; 3) AA3 (1,5 eq.), DIC (1,5 eq.), HOAt (1,5 eq.), DCM (4 mL), 20 °C, 12 h; 20% de piperidina em THF, 20 °C, 2 h; 4) AA4 (1,5 eq.), DIC (1,5 eq.), HOAt (1,5 eq.), DCM (4 mL), 20 °C, 12 h; 20% de piperidina em THF, 20 °C, 2 h; 5) AA5 (1,5 eq.), DIC (1,5 eq.), HOAt (1,5 eq.), DCM (4 mL), 20 °C, 12 h; 20% de piperidina em THF, 20 °C, 2 h; 6) AA6 (1,5 eq.), DIC (1,5 eq.), HOAt (1,5 eq.), DCM (4 mL), 20 °C, 12 h; 20% de piperidina em THF, 20 °C, 2 h; 7) AA7 (1,5 eq.), DIC (1,5 eq.), HOAt (1,5 eq.), DCM (4 mL), 20 °C, 12 h; 20% de piperidina em THF, 20 °C, 2 h; 8) AA8 (1,5 eq.), DIC (1,5 eq.), HOAt (1,5 eq.), DCM (4 mL), 20 °C, 12 h; 20% piperidine in THF, 20°C, 2 h; 9) AA9 (1.5 eq.), DIC (1.5 eq.), HOAt (1.5 eq.), DCM (4 mL), 20 °C, 12 h; 20% piperidine in THF, 20°C, 2 h; 10) AA10 (1.5 eq.), DIC (1.5 eq.), HOAt (1.5 eq.), DCM (4 mL), 20 °C, 12 h; 11) TFA cocktail (TFA:Tips: H2O = 95:2.5:2.5), 20 °C, 1.5 h. Figure 5 (cont.) Petition 870250075820, dated 08 / 27 / 2025, p. 409 / 438 18 / 45 Figure 6 N-Fmoc-Tag5-2AA Tag5-2AA Petition 870250075820, dated 08 / 27 / 2025, p. 410 / 438 19 / 45 Figure 6 (cont.) N-Fmoc-Tag5-4AA Tag5-4AA Petition 870250075820, dated 08 / 27 / 2025, p. 411 / 438 20 / 45 Figure 6 (cont.) N-Fmoc-Tag5-6AA Tag5-6AA Petition 870250075820, dated 08 / 27 / 2025, p. 412 / 438 21 / 45 Figure 6 (cont.) Petition 870250075820, dated 08 / 27 / 2025, p. 413 / 438 22 / 45 Figure 6 (cont.) Boc-PEG8-linker Petition 870250075820, dated 08 / 27 / 2025, p. 414 / 438 23 / 45 Figure 6 (cont.) Petition 870250075820, dated 08 / 27 / 2025, p. 415 / 438 24 / 45 Figure 7 Petition 870250075820, dated 08 / 27 / 2025, p. 416 / 438 25 / 45 Figure 7 (cont.) N-Fmoc-Tag5-5AA Tag5-5AA Petition 870250075820, dated 08 / 27 / 2025, p. 417 / 438 26 / 45 Figure 7 (cont.) N-Fmoc-Tag5-7AA Tag5-7AA Petition 870250075820, dated 08 / 27 / 2025, p. 418 / 438 27 / 45 Figure 7 (cont.) Tag5-8AA N-Fmoc-Tag5-9AA Petition 870250075820, dated 08 / 27 / 2025, p. 419 / 438 28 / 45 Figure 7 (cont.) Tag5-10AA Petition 870250075820, dated 08 / 27 / 2025, p. 420 / 438 29 / 45 Figure 7 (cont.) Tag5-21 Petition 870250075820, dated 08 / 27 / 2025, p. 421 / 438 30 / 45 Figure 7 (cont.) Petition 870250075820, dated 08 / 27 / 2025, p. 422 / 438 31 / 45 Chloromethylated polystyrene polymer abbreviated as PEG (molecular weights from 2000 to 20000) Figure 8 Petition 870250075820, dated 08 / 27 / 2025, p. 423 / 438 32 / 45 Figure 8 (cont.) A series of hydrophobic benzyl alcohol tags Petition 870250075820, dated 08 / 27 / 2025, p. 424 / 438 33 / 45 Figure 8 (cont.) 10n20 Petition 870250075820, dated 08 / 27 / 2025, p. 425 / 438 34 / 45 Figure 9 Petition 870250075820, dated 08 / 27 / 2025, p.426 / 438 35 / 45 Figure 10A LC-MS method -< -<í < EÜ rt ffi 1 MS enconliBda (M+H|* [&>;*! ί ΐΐΐ % i à I s 5 eS hn P I-- ó í- w ® 3.E §B § 1^2 UXÍ-XAG·»^· ITBS+Híf jjj ώ £ •XJ — a§ A 6 J5 gâ í?3 síã wí P 1'8 r! 'Λόό fl ã r 3 Wl* 1 Tm5- 7AA |_« Á ςΦ cru & i TwL 1 1CÁA Clicue com F EGi-ljnkaf |3 eq.) xn THF, CuSX 1.5 eq.) a ΊΠΤΑίί^Ιί1^· T^F·^ μΊ>3]ϊ^ eq.) ·5πτΗ_Ο, b lernperftura JHitanEn p:c 12 Ιέώα ML □jvafem c-onr ccqurfel ciTFA ÇWA / TIFS.·'H>[>SM 175,51 am DCM [37', 1 CO: Ml ul. 2[Fi?. I2h 2014 ít etec fite ΡΠΊ THF “4 Φ F| Q 9 ri ΓΙ O FJ m 1 °e ÍlÍ A “1 A - L. Reaçao üb acoplamento de am ida «1 * ΓΙ £ * ir. j: ,* ti J® c4 4 ί ΞΓ * DQ s: .· & Ê » M ui -· -.1 s JfOÀi 1 Ϊ Λ í •»n: Ϊ Wi P4 E Vi fo 8 F 5 J 5-d Ώ r fh ΐ Vi é n hF% ί 35 eq E !.& BJ. 35 si. FE r anin Mcida 1.5 eq. 8 l.íeq 15 eq. E É e w- »5 [ É 1 5«| í J á3 S3 « 3 70S AA7 3 sw O .1·= LLl * m 'ME 4 rr M = Petição 870250075820, de 27 / 08 / 2025, pág.427 / 438 36 / 45 Figure 10B ή OJ. ii £ 3 .4 3 « 9i £ 3 £ í • n » Oi 4 3 20¾ ds enn THF > o ri O ri oo ri o ri > s -> rt O ri c rj 'n & i S ü 1 O TS er Ή s: Ί. *UhKH€O LL1D3 □ ϊόΒΓΤ'Α s 3* tf tf 'Tr tf £ F & tf ΓΪ tf ^1 |F l- Q tf S' tf Ifb ih Ώ i 1 ff Th ro tf tf tf F | 1 arrinoBcidü tf tf hi tf £ g- -Hi *“! Γ o tf tf tf 3 3 tn P 5 VI e<l· 3 í ώ M í o> 5 if í QOECE rj ou H 4 * b4 — e 4 4- .. Petição 870250075820, dated 27 / 08 / 2025, pág. 428 / 438 37 / 45 Figure 11A Produtc ME RcirarlrnrlníMl-lO· Apás CEivagcm ptri rarrover TngE n Jri ρ-riR fiíTdFdík*^ £ i έ s 3 a íS £ g tl n à a IML? [M-IAG-lBl· ni5 + 4Hf 3 hi Γ- t i- Ά SP — nj 4 »| » ΡΊΡ fl á ί Í? 2$ IjM.JEiM-IAUi'Wa-i'IBS- D^+'H1 _ § ®-. Ó i=- Í? K d D^Tr'B <K*iotti: 1AA Wr •CWI WS íi»l Xí τ*Α ÍÀÀ Tâ|!<. 10AA 1— £ |V i ta 1 .n^dc t> u'1w0i iLa pul· |ji <iii io do· AMJ ] II? «(·. -± Ϊ N s «»ϊγ. f-r 3 31 V s κ$ [Jt 1 £ » -± £ JHli 1UB SUip i -PSBÍ3i ap MiQE 1 F > £ > ü ri ADÍ > > Ft > Ο ri ΰ '4 ReflCBO-cs clique Etapa ΐ < ϋ.X Keaçáode acoplEraerto d« smtde müLBí por7e£t ÍD.íM rrmcll 111 t* 3 * r 5 £ & £ í & £ έ & » £ϊ Μ M* m £ f* -Í n —FI— 1—* —F ο Ρ*Τ; -h •n ri r< tj Q — •*h ΓΉ -η Ό - Am rmscido H· ρ·β *Ί ο rf= — — 5 3 AA3 IBi ÀA4 I 3 ϋΊ ÍB ? $3 n * Í Etapa r.° M j É ή- H -fc_L Petição 870250075820, dated 08 / 27 / 2025, pág. 429 / 438 38 / 45 Figure 11B Petição 870250075820, de 27 / 08 / 2025, pág. 430 / 438 39 / 45 Figure 12 3 3 3 MS-on-o-nivti-Bjd-0- -^1+-H)' Apáa divagam pnu remai / ar TagE e drupos prctetore-B j Λ á £ 4 B zc w. F 1 P 44 Ê f Ü h jé is h £ I1 I439J0 |itTAtWM!MÜI3i»-7ΗΓ i μλ λ |Μ-τλσζχ<κ.κ7τκ. ΙΒ^ΓΚ-ΜΓ______ «fl.» |[\tTAG.Trt4FMB-mS· BoíMÍtt-IClH?· Ê í a í Q 3 c 1 fc 1 í i jj í j í '» í Λ J í 4Í£ s P·1 raprasanta 1 dasokenb per inure da AA#] 1! u ^L1 T] 'gl mz Ã Ϊ « o- T íf T_ £ f > z SD a W / σ> § — D iL Λ rq í 3 ry “1 Π PX Ê E p ·*γ cr ET ΙΠ η s“ H 5 £ ü □ □ wd Ti [í ee μP -1 5 D 3 J ! D yu D Ü.« 'B k K Ή ftaaçáo ae molar deamkla coupling by Tag5 (¢.04 rnmal) O í a í t £ & / -J 3 & í í s 5 / 8 á h * I * « a ϊ> o 5 * ái VL o Wi o mi RT. o 2 rri VL OP s 3 O 43 5 5 PD — Hj mt? “3 3 R. ? ÉS £3 í b » •w 4C E * L Petition 870250075820, dated 08 / 27 / 2025, pp. 431 / 438 40 / 45 Route Stages Total Yield Large Quantity Commercial SMs Purification Stages Reported in Patent Scale-up Challenge Column Suspension Rt 1 AA2 10 6~9% YES 6 / YES Route 1 is the longest route. Rt 2 AA2 9 3.9% YES 4 2 No Route 2 includes two difficult stages: purification is very difficult in the 3rd stage, and the yield in the Suzuki reaction in the 5th stage is low and purification is also difficult. Rt 3 AA2+ Link r 9 for AA2 23% YES 4 1 No Route 3 includes two stages with low yields. In the stage 3, compound 3 was easily converted by dehalogenation and difficult to purify.In step 5, the Suzuki reaction of compound 6 to compound 7 is also difficult to purify via silica gel column. 10 for AA2+Linker 28.7% for the last step 1 / Rt 4 AA2 8 15.2% NO N / AN / A No Route 4 has only 8 steps. It also avoids the dangerous hydrogenation operation. But no supplier provides large quantities of SM (4-bromo-3-ethylphenol). Figure 13 Petition 870250075820, dated 08 / 27 / 2025, p. 432 / 438 41 / 45 Route Steps Total Yield Large Quantity Commercial SMs Purification Steps Reported in Patent Scale-Up Challenge Suspension Column Rt 5 AA2+ Linker 8 to AA2 31.09% YES 6 No Route 5 is route 3 optimized with modifications to reduce the double bond before the Suzuki reaction, because the double bond in Cmpd 3 is also the reaction site in the formation of the CC bond in the Pd catalyst, which is not suitable for scale-up. Route 5 is used to generate 3.5 kg of AA2+Linker.9 for AA2+Linker 75.8% for the last step YES 1 / No Figure 13 (cont.) Petition 870250075820, dated 08 / 27 / 2025, p. 433 / 438 42 / 45 Figure 14 Petition 870250075820, dated 08 / 27 / 2025, p. 434 / 438 43 / 45 Figure 14 (cont.) Petition 870250075820, dated 08 / 27 / 2025, p. 435 / 438 44 / 45 Reagents and conditions: (a) K2CO3, PMB-C1, DMF, 25 °C, 12 h; (b) Ph3PCH2Br, t-BuOK, THF, 0-25°C, 4h, 71.91%; (c) Pd(dppf)Cb, KOAc, 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2dioxaborolane, 1,4-dioxane, 80°C, 20h, 42.75%; (d) aa 2-6, K2CO3, Pd(PPh3)4, 1,4-dioxane and H2O, 80 °C, 2.5h, 76.20%; (e) Pd / C, H2 (15 psi (103.4 kPa)), MeOH, 25°C, 48 h, 85.01%; (f) K2CO3, 1-chloro-4-iodobutane, DMF, 50°C, 12 h, 79.2%; (g) K2CO3, KI, NaN3, DMF, 50 °C, 7 h. (h) LiOH (2.0 eq.), THF / H2O (2:1), 0 ~25°C, 1 h, (i) HCl / EtOAc; (j) HCl / EtOAc; (k) Fmoc-Osu (1.0 eq.), NaHCO3 (2.0 eq.), THF / H2O (2:1), 25°C, 12 h. 65.44% in 4 stages in total; (1) Py, Tf20, DCM, 0 °C, 1 h. Figure 14 (cont.Petition 870250075820, dated 08 / 27 / 2025, pp. 436 / 438 45 / 45 Reagents and conditions: a) Bu4N+Br3 (1.04 eq.) in DCM (3 V) / MeOH (2 V), 20 °C, 2 h, yield of 92.4%; b) PBin2 (1.2 eq.), Pd(OAc)2 (0.02 eq.), PCy3 (0.04 eq.), KOAC (2.0 eq.) in dioxane (10 V), 90 °C, 4 h, yield of 75.8%; c) 3 (1.2 eq.), 4-azidobutan-1-ol (1.0 eq.), PPh3 (1.2 eq.), DIAD (1.2 eq.), Molecular sieve 4A (0.25 eq.) in THF (10 V), 0-20 °C, 3.5 h, 35.9% yield; d) 4a (1.1 eq.), K2CO3 (2.0 eq.), Pd(dppf)Cl2-DCM (0.1 eq.) in H2O / iPrOH (1 / 4, 10 V), 50 °C, 12 h, 22.8% yield; e) 5a (2.0 eq.), HOVc (1.8 eq.), CuSO4.5H2O (1.28 eq.), THF (30 V), 100 °C, 1 h, microwave. Final product AA2+Linker ESI-MS: calculated m / z 1111.57, found 1112.60 [M+H]+.

Images