NPY2 receptor agonists

Abstract

The present invention relates to PYY analogs having an alanine at position 4, a lysine at position 7, a QRY at the C-terminus, and a half-life extending group. The analogs of the present invention are soluble at pH around 6 and 7. The present invention also relates to pharmaceutical compositions containing such PYY analogs and pharmaceutical uses of the analogs.

Description

[Technical Field]

[0001] The present invention relates to PYY analogs that are neuropeptide Y2 (NPY2) receptor agonists and their medical uses in the treatment and / or prevention of various diseases, conditions, or disorders, such as the treatment and / or prevention of excessive food intake, excess weight, obesity, metabolic disease, and other conditions or disorders associated with excess weight or obesity, such as diabetes and cardiovascular disease. [Background technology]

[0002] Excess weight and obesity are defined as abnormal or excessive body fat accumulation that presents a risk to health. In this regard, excess weight and obesity are major risk factors for several chronic diseases, including type 2 diabetes, cardiovascular disease, and cancer. According to the WHO, excess weight and obesity are no longer considered a problem limited to high-income countries and are now increasing dramatically in low- and middle-income countries. The WHO Global Health Observatory indicates that in 2016, 39% of women and men aged 18 years and older were overweight, and 11% of men and 15% of women were obese.

[0003] Despite years of efforts, the number of people with overweight and obesity continues to increase. First-line treatments for overweight and obese patients include diet and exercise, but are often not fully effective. Second-line treatments are bariatric surgery and drug therapy. Available pharmacological treatments appear to lack efficacy and / or safety, and only a limited number of approved treatments are available in the United States and Europe. Therefore, there remains a high medical need for more effective and safe treatment options. NPY (neuropeptide Y, SEQ ID NO: 1 - human sequence), PYY (peptide YY, SEQ ID NO: 2 - human sequence), and PP (pancreatic polypeptide, SEQ ID NO: 3 - human sequence) are naturally secreted homologous 36 amino acid C-terminally amidated peptides that belong to the PP-fold family of peptides. Sequence of hPYY(3-36): Ile Lys Pro Glu Ala Pro Gly Glu Asp Ala Ser Pro Glu Glu Leu Asn Arg Tyr Tyr Ala Ser Leu Arg His Tyr Leu Asn Leu Val Thr Arg Gln Arg Tyr (SEQ ID NO: 4)

[0004] PYY is cleaved to PYY(3-36) by dipeptidyl peptidase IV (DPP IV). Compared with PYY(1-36), PYY(3-36) exhibits increased selectivity for the neuropeptide Y2 receptor over the neuropeptide Y1, Y4, and Y5 receptors, while retaining some Y1 and Y5 affinity. PYY or PYY(3-36) is thought to exert its anorectic effect via activation of the neuropeptide Y2 receptor (Inhibition of Food Intake in Obese Subjects by Peptide YY 3-36 , N Engl J Med 2003;349;941-8). However, PYY and even PYY(3-36) have short half-lives in the body and exhibit undesirable chemical or physical properties, such as poor stability, and their pharmacological effects, such as their effectiveness as weight loss agents, appear to be limited. International Publication No. WO2014 / 178018 discloses PYY analogues and their ability to reduce food intake in mice. International Publication Nos. WO2011 / 033068 and WO2011 / 058165 disclose long-acting Y2 receptor agonists. International Publication Nos. WO 2015 / 071355, WO 2016 / 198682, and WO 2020 / 092191 relate to PYY compounds that are selective Y2 receptor agonists. These publications disclose PYY compounds that contain covalently attached substituents or modifying groups, also referred to as extension moieties.

[0005] There is a need in the art for additional (long-acting) PYY analogues that selectively act on NPY2 receptor.For example, it would be desirable to further increase the solubility of PYY analogues, preferably increase the solubility at around pH 7 and / or pH 6.This would increase the formulation options for ready-to-use application, and possibly allow them to be combined with other (peptide) therapeutic agents to improve efficacy. The PYY analogs of the present invention have generally been found to be soluble at around pH 6 and pH 7. Summary of the Invention

[0006] In a first aspect, the present invention provides a PYY analogue comprising: i) an alanine at a position corresponding to position 4 of hPYY(3-36); ii) a lysine at a position corresponding to position 7 of hPYY(3-36); iii) the sequence QRY at its C-terminus Including, a half-life extending group is attached to the epsilon amino group of lysine at position 7, or to the epsilon amino group of lysine at positions 6, 10, 11, 14, 17, 21, 22, or 30, or to the carboxylic acid group of the side chain of aspartic acid or glutamic acid at positions 14 or 30; Provides PYY analogues.

[0007] In some embodiments, the PYY analog is i) an alanine at a position corresponding to position 4 of hPYY(3-36); ii) a lysine at a position corresponding to position 7 of hPYY(3-36); iii) glutamic acid at a position corresponding to position 9 of hPYY(3-36); iv) a tyrosine at a position corresponding to position 20 of hPYY(3-36); v) tryptophan at a position corresponding to position 30 of hPYY(3-36); vi) a leucine at a position corresponding to position 31 of hPYY(3-36); vii) the sequence RQRY at its C-terminus Including, The half-life extending group is attached to the epsilon amino group of lysine at position 7, or to the epsilon amino group of lysine at positions 6, 10, 11, 14, 17, 21, or 22, or to the carboxylic acid group of the side chain of aspartic acid or glutamic acid at position 14.

[0008] In some embodiments, the PYY analog is i) an alanine at a position corresponding to position 4 of hPYY(3-36); ii) a lysine at a position corresponding to position 7 of hPYY(3-36); iii) glutamic acid at a position corresponding to position 9 of hPYY(3-36); iv) a tyrosine at a position corresponding to position 20 of hPYY(3-36); v) the sequence WLTRQRY at its C-terminus Including, The half-life extending group is attached to the epsilon amino group of lysine at position 7, or to the epsilon amino group of lysine at positions 6, 10, 11, 14, 17, 21, or 22, or to the carboxylic acid group of the side chain of aspartic acid or glutamic acid at position 14. In some embodiments, the PYY analog is according to one of the above embodiments and has a half-life extending group attached to the epsilon amino group of the lysine at the 7-position.

[0009] In some embodiments of the invention, the PYY analog has the formula: R 1 -ZR 2 wherein R 1 is hydrogen, -C(O)C 1-6 Alkyl, -C(O)C6H6, -C(O)C 3-6 Cycloalkyl, -C(O)C 1-6 Alkyl-C3-6 Cycloalkyl, or C 1-6 Alkyl, or C 1-6 Alkyl-C 3-6 is cycloalkyl, R 2 OH or NHR 3 where R 3 is hydrogen or C 1-3 is alkyl, Z is an amino acid sequence of Formula III: Ala-Pro-X6-Lys-Pro-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-Tyr-X21-Val-X23-Leu-Arg-His-Tyr-Tyr-Asn-Trp-Leu-Thr-Arg-Gln-Arg-Tyr(III) and During the ceremony, X6 is selected from the group consisting of Ala and Glu; X9 is selected from the group consisting of Glu and Gly; X10 is selected from the group consisting of Ala and Glu; X11 is selected from the group consisting of Ala, Asp, Glu, and Pro; X12 is selected from the group consisting of Ala and Ser; X13 is selected from the group consisting of Ala, Glu, Ser, Thr, and Pro; X14 is selected from the group consisting of Ala, Glu, and Pro; X15 is selected from the group consisting of Ala and Glu; X16 is selected from the group consisting of Ala and Glu; X17 is selected from the group consisting of Ile, Leu, Thr, and Val; X18 is selected from the group consisting of Glu and Gln; X19 is selected from the group consisting of Ala, Glu, Arg, Lys, and Gln; X21 is selected from the group consisting of Glu and Tyr; X23 is selected from the group consisting of Ala, Glu, Ser, and Thr; The half-life extending group is attached to the epsilon amino group of the lysine at position 7. In some embodiments, the half-life extending group consists of a lipophilic substituent X and a linker U, wherein the linker U is attached to an amino acid side chain, and the X is attached to U, and the linker U consists of one, two, or three sub-moieties (U1, U2, U3).

[0010] In some embodiments, the lipophilic substituent X is selected from the group consisting of 15-carboxy-pentadecanoyl, 17-carboxy-heptadecanoyl (C18DA), and 19-carboxy-nonadecanoyl, and the linker U consists of one, two, or three submoieties independently selected from the group consisting of Gly, Glu, γ-Glu, ε-Lys, Ser, and OEG, or independently selected from the group consisting of γ-Glu and OEG. In some embodiments, the PYY analog is selected from compounds 1-244 described herein. In some embodiments, the PYY analog is in the form of a salt, preferably a pharmaceutically acceptable salt. The present invention further provides compositions comprising the PYY analogs described herein. The present invention further provides PYY analogs for use in methods of medical treatment, e.g., for use in the treatment of obesity and various obesity-related conditions, diseases, or disorders, e.g., type 2 diabetes, NAFLD, or NASH. The present invention provides PYY analogs of the present invention for use in methods for treating, preventing, or reducing weight gain, promoting weight loss, and / or reducing excess weight. DETAILED DESCRIPTION OF THE INVENTION

[0011] Terms, definitions, and conventions Terms not specifically defined herein shall be given the meaning ordinarily given by one of ordinary skill in the art in light of this disclosure and the context. However, as used herein, unless otherwise indicated, the following terms have the indicated meanings and are subject to the following conventions: Throughout this specification, the amino acid positions of the PYY analogs are numbered according to the corresponding positions in native human PYY, the sequence of which is shown above.

[0012] PYY Analog A PYY analog is a peptide containing an amino acid sequence corresponding to the amino acid sequence of hPYY(3-36). In other words, a PYY analog is a peptide whose structure is related to PYY and in which one or more amino acid residues have been modified compared to hPYY(3-36). Possible modifications include substitution, insertion, or deletion of amino acids at specific positions. The PYY analog of the present invention relates to a peptide that retains a certain binding affinity (Ki) for the hNPY2 receptor. The term "PYY analogue" includes the peptide itself, as well as the peptide in an ionized state (eg, when one or more of the side chains of its amino acids are ionized, ie, (de)protonated). The term "PYY analog" can also refer to a peptide in which a half-life extending group is attached to one or more amino acids of the peptide. In such cases, the side chain of the amino acid has a covalently attached half-life extending group.

[0013] As used herein, the term "pharmaceutically acceptable salt" is intended to refer to a salt that is not harmful to the patient or subject to whom the salt in question is administered. It may suitably be, for example, a salt selected from an acid addition salt and a base salt. As used herein, "pharmaceutically acceptable salt" refers to a derivative of the disclosed analogs or compounds in which the parent analog or compound is modified by making an acid or base salt thereof. Examples of acid addition salts include chloride salts, citrate salts, and acetate salts. Examples of base salts include salts in which the cation is an alkali metal cation, for example, sodium or potassium ion, an alkaline earth metal cation, for example, calcium or magnesium ion, and a substituted ammonium ion, for example, N(R 1 )(R 2 )(R 3 )(R 4 ) + Ions of type (wherein R 1 , R 2 , R 3 , and R 4 are independently typically hydrogen or optionally substituted C 1-6 -alkyl). Other examples of pharmaceutically acceptable salts include those described in "Remington's Pharmaceutical Sciences", 17th edition, Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, PA, USA, 1985 (and later editions), "Encyclopaedia of Pharmaceutical Technology", 3 rd edition, James Swarbrick (Ed.), Informa Healthcare USA (Inc.), NY, USA, 2007, and in J. Pharm. Sci. 66: 2 (1977). The term "agonist", as used in the context of the present invention, refers to a substance that activates the receptor type in question, typically by binding to it (ie, as a ligand). Each embodiment of the present invention described herein may be used alone or in combination with one or more other embodiments of the present invention.

[0014] Throughout this specification, naturally occurring amino acids are designated by their conventional three-letter or one-letter abbreviations (e.g., Ala or A for alanine, Arg or R for arginine, etc.), unless they are referred to by their full name (e.g., alanine, arginine, etc.). Unless otherwise indicated, reference is made to the L-isomer form of the amino acid in question.

[0015] Additional abbreviations are as follows: Hyp: 4-hydroxyproline, e.g., (2S,4R)-4-hydroxyproline [also referred to as (4R)-4-hydroxy-L-proline] γ-Glu: γ-glutamic acid (also referred to as gGlu)

[0016] "C 1-n The term "alkyl", alone or in combination with another radical, refers to an acyclic, saturated, branched or straight-chain hydrocarbon radical having 1 to n C atoms, where n is an integer selected from 2, 3, 4, 5, or 6. For example, C 1-5 The term -alkyl encompasses the radicals HC-, HC-CH-, HC-CH-CH-, HC-CH(CH)-, HC-CH-CH-CH-, HC-CH(CH)-, HC-CH(CH)-CH-, HC-C(CH)-, HC-CH-CH-CH-, HC-CH-CH-CH-, HC-CH-CH-CH(CH)-, HC-CH-CH(CH)-, HC-CH-CH(CH)-CH-, HC-CH(CH)-CH-, HC-CH-C(CH)-, HC-C(CH)-CH-, HC-CH(CH)-CH(CH)-, and HC-CH-CH(CHCH)-. "C 3-nThe term "cycloalkyl", where n is an integer from 4 to n, alone or in combination with another radical, refers to a cyclic, saturated, unbranched hydrocarbon radical having 3 to n C atoms. For example, C 3-6 The term -cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. "C(O)" or "C(=O)" refers to a carbonyl group.

[0017] Compound nomenclature For example, iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PGEDASPEELQRYYVSLRHYYNALTRQRY-NH2 (Wherein, iVal represents 3-methylbutanoyl (—C(O)CHCH(CH)), C18DA stands for 17-carboxyheptadecanoyl, gGlu represents L-γ-glutamyl connected to C18DA through its amino group and to OEG1 through its γ-carboxy group; OEG1 represents 2-[2-(2-aminoethoxy)ethoxy]acetoyl, connected to gGlu through its amino group and to OEG2 through its carboxy group; OEG2 represents 2-[2-(2-aminoethoxy)ethoxy]acetoyl, which is connected to OEG1 through its amino group and to the ε-amino group of lysine (K) through its carboxy group. fully defines a PYY analogue of the following structure:

[0018] [ka]

[0019] Alternatively, the same compound can be defined in the following manner: N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,18Q,22V,28Y,30A,31L]hPYY(4-36).

[0020] The term "treatment" and grammatical variations thereof (e.g., "treated," "treating," "treating") as used in this context refers to an approach for obtaining beneficial or desired clinical results. For purposes of this invention, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, attenuation of the extent of the disease, stabilization of the disease state (i.e., not worsening), delay or slowing of disease progression, alleviation or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. "Treatment" can also mean prolonging survival as compared to expected survival in the absence of treatment. A subject (e.g., a human) in need of treatment may therefore be one already suffering from the disease or disorder in question. The term "treatment" includes preventing or reducing the increase in the severity of a pathology or symptom (e.g., weight gain or hyperglycemia) as compared to the absence of treatment, and is not necessarily meant to indicate a complete cessation of the associated disease, disorder, or condition.

[0021] The term "prevention" and its grammatical variants (e.g., "prevented," "preventing," "preventing") as used in the present context refers to an approach for hindering or preventing the development of a condition, disease, or disorder, or for altering its etiology. Thus, "prevention" can refer to prophylactic or preventive measures. For the purposes of the present invention, beneficial or desired clinical results include, but are not limited to, the prevention or delay of disease symptoms, progression, or development, whether detectable or undetectable. A subject (e.g., a human) in need of "prevention" may be one who is not yet afflicted with the disease or disorder in question. The term "prevention" includes arresting or delaying the onset of a disease compared to the absence of treatment, and is not necessarily meant to indicate permanent prevention of the associated disease, disorder, or condition.

[0022] Half-life extender As described herein, the half-life extending group is covalently attached to a functional group in the side chain of an amino acid of a PYY analog. The half-life extending group comprises or consists of a lipophilic substituent (X) and, optionally, a linker (U), where one end of the linker U, if present, is attached to the amino acid of the PYY analog and the other end is connected to the lipophilic substituent (-UX). Without wishing to be bound by any particular theory, it is believed that such lipophilic substituents (and other classes of half-life extending moieties) bind to albumin and other plasma components in the bloodstream, thereby protecting the compounds of the invention from renal infiltration and enzymatic degradation, and thus potentially enhancing the half-life of the compounds in vivo. Lipophilic substituents may also modulate the efficacy of the compounds as agonists for the NPY2 receptor or for other receptors in the NPY receptor family.

[0023] The lipophilic substituent X is attached to the linker U via an ester, ether, sulfonyl ester, thioester, amide, amine, triazole, or sulfonamide. It will therefore be understood that the lipophilic substituent X preferably comprises an acyl group, a sulfonyl group, an alkyne, an azide, an N atom, an O atom, or an S atom that forms part of the ester, sulfonyl ester, thioester, triazole, amide, amine, or sulfonamide. Preferably, the acyl group, or the O or N atom in the lipophilic substituent X forms part of the amide or ester together with the linker U. The half-life extending group (and its linker U, if present) is attached to the amino acid residue of the PYY analogue via an ester, sulfonyl ester, thioester, amide, amine, or sulfonamide. It will therefore be understood that the half-life extending group (and its linker U, if present) preferably comprises an acyl group, sulfonyl group, N atom, O atom, or S atom that forms part of the ester, sulfonyl ester, thioester, amide, amine, or sulfonamide. Preferably, the acyl group, or the O or N atom in the linker U forms part of an amide or ester together with the amino acid residue.

[0024] The lipophilic substituent X may comprise a hydrocarbon chain having 10 to 24 carbon atoms, e.g., 14 to 22 carbon atoms, e.g., 16 to 20 carbon atoms. Preferably, it has at least 14 carbon atoms, and preferably 20 or fewer carbon atoms. For example, the hydrocarbon chain may contain 14, 15, 16, 17, 18, 19, or 20 carbon atoms. The hydrocarbon chain may be linear or branched, saturated or unsaturated. Furthermore, the hydrocarbon chain may contain a functional group, e.g., a carboxylic acid group, a sulfonic acid group, or a tetrazole group, at its terminus. From the above discussion, it will also be understood that the hydrocarbon chain is preferably substituted with a moiety that forms part of the bond to an amino acid residue of the PYY analog or the linker U, e.g., an acyl group, a sulfonyl group, an N atom, an O atom, or an S atom.

[0025] Most preferably, the hydrocarbon chain is substituted with an acyl group (e.g., for attachment to the linker U), and thus the hydrocarbon chain may be part of an alkanoyl group, such as dodecanoyl, 2-butyloctanoyl, tetradecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl, or eicosanoyl group. These hydrocarbon chains substituted with an acyl group at one end may be further functionalized with a carboxylic acid group at the other end of the chain. Examples of functionalized hydrocarbon chains (e.g., lipophilic substituent X) are 15-carboxy-pentadecanoyl, 17-carboxy-heptadecanoyl, and 19-carboxy-nonadecanoyl.

[0026] In certain embodiments, the linker moiety U may itself be one, two, three, or more linked submoieties (U 1 , U 2 , U 3In some of these embodiments, the linker may include one or more (e.g., one, two, or three) linked amino acid residues, each independently a residue of any naturally occurring or non-naturally occurring amino acid. For example, the linker may include one, two, or three linked amino acid residues, each independently a residue of any naturally occurring or non-naturally occurring amino acid, such as Gly, Pro, Ala, Val, Leu, Ile, Cys, Phe, Tyr, His, Lys, Arg, Gln, Asn, α-Glu, γ-Glu, ε-Lys, Asp, β-Asp, Ser, Thr, Aib, AEA (2-(2-aminoethoxy)acetic acid), AEEEA (2-{2-[2-(2-aminoethoxy)acetic acid), [ethoxy]ethoxy}acetic acid), H2N-dPEG(4)-COOH (15-amino-4,7,10,13-tetraoxa-pentadecanoic acid), H2N-dPEG(6)-COOH (1-amino-3,6,9,12,15,18-hexaoxaheneicosan-21-oic acid), H2N-dPEG(12)-COOH (1-amino-3,6,9,12,15,18,21,24,27,30,33,36-dodecaoxanoic acid), natriacontan-39-oic acid), OEG-OEG (2-[2-(2-{2-[2-(2-aminoethoxy)ethoxy]acetamido}ethoxy)ethoxy]acetic acid), H-Ebes (3-({2-[2-(2-aminoethoxy)ethoxy]ethyl}carbamoyl)propanoic acid), H-DOOA-DIG-OH (2-[({2-[2-(2-aminoethoxy)ethoxy]ethyl}carbamoyl)methoxy]acetic acid), H-TTD It may be a residue of -DIG-OH (2-{[(3-{2-[2-(3-aminopropoxy)ethoxy]ethoxy}propyl)carbamoyl]methoxy}acetic acid), H-TTDS-OH (3-[(3-{2-[2-(3-aminopropoxy)ethoxy]ethoxy}propyl)-carbamoyl]propanoic acid), or 8Ado (i.e., 8-amino-3,6-dioxaoctanoyl, also referred to herein as OEG).

[0027] References to γ-Glu, ε-Lys, and β-Asp refer to amino acid residues that participate in the bond via their side chain carboxyl or amine functional groups. Thus, γ-Glu and β-Asp participate in the bond via their alpha amino and side chain carboxyl groups, while ε-Lys participates via its carboxyl and side chain amino groups. In the context of the present invention, γ-Glu, gGlu, and isoGlu are used interchangeably.

[0028] In certain embodiments, the linker U is comprised of one, two, or three independently selected submoieties (U) selected from the group consisting of Ala, Glu, γ-Glu, Gly, ε-Lys, Ser, OEG, and OEG-OEG. 1 , U 2 , U 3 ) or consisting of it. Preferred are linkers consisting of γ-Glu, γ-Glu-γ-Glu, γ-Glu-OEG, OEG-OEG, γ-Glu-γ-Glu-OEG or γ-Glu-OEG-OEG.

[0029] Synthesis of PYY analogues The present invention provides methods for synthesizing the PYY analogs of the present invention. PYY analogs can be produced by standard synthetic methods, including standard solid-phase or solution-phase methods. Peptides are assembled either stepwise or by combining fragments, and optionally isolated and purified to obtain the final peptide product. Examples of synthesis are found in Fields, GB et al., "Principles and Practice of Solid-Phase Peptide Synthesis" in Synthetic Peptides, Grant GA (ed.), Oxford University Press (2002). nd The paper has been described in numerous publications, including the "Earthquake and Phenomena in the Early Stages of the American Civil War" (Earthquake and Phenomena in the Early Stages of the American Civil War, 2002).

[0030] Embodiment In a first aspect, the present invention provides a PYY analogue comprising: i) an alanine at a position corresponding to position 4 of hPYY(3-36); ii) a lysine at a position corresponding to position 7 of hPYY(3-36); iii) the sequence QRY at its C-terminus Including, a half-life extending group is attached to the epsilon amino group of lysine at position 7, or to the epsilon amino group of lysine at positions 6, 10, 11, 14, 17, 21, 22, or 30, or to the carboxylic acid group of the side chain of aspartic acid or glutamic acid at positions 14 or 30; Provides PYY analogues. In some embodiments, the PYY analog contains a glutamic acid at the position corresponding to position 9 of hPYY(3-36). In some embodiments, the PYY analog contains a tyrosine at a position corresponding to position 20 of hPYY(3-36). In some embodiments, the PYY analog contains tryptophan at the position corresponding to position 30 of hPYY(3-36). In some embodiments, the PYY analog contains a leucine at a position corresponding to position 31 of hPYY(3-36). In some embodiments, the PYY analog contains an arginine or lysine at a position corresponding to position 33 of hPYY(3-36). In some embodiments, the PYY analog has a half-life extending group attached to the epsilon amino group of the lysine at the 7-position. In some embodiments of the invention, the half-life extending group consists of a lipophilic substituent X and a linker U, wherein said linker U is attached to an amino acid side chain and said X is attached to U. In some embodiments, the lipophilic substituent X is selected from the group consisting of 15-carboxy-pentadecanoyl, 17-carboxy-heptadecanoyl (C18DA), and 19-carboxy-nonadecanoyl. In some embodiments, the linker U comprises one or more submoieties, and at least one of the submoieties is OEG. In some embodiments, the linker U consists of one, two, or three submoieties (U1, U2, U3), each independently selected from the group consisting of Gly, Glu, γ-Glu, ε-Lys, Ser, and OEG.

[0031] In some embodiments, the PYY analog is i) an alanine at a position corresponding to position 4 of hPYY(3-36); ii) a lysine at a position corresponding to position 7 of hPYY(3-36); iii) glutamic acid at a position corresponding to position 9 of hPYY(3-36); iv) a tyrosine at a position corresponding to position 20 of hPYY(3-36); v) tryptophan at a position corresponding to position 30 of hPYY(3-36); vi) a leucine at a position corresponding to position 31 of hPYY(3-36); vii) the sequence RQRY at its C-terminus Including, The half-life extending group is attached to the epsilon amino group of lysine at position 7, or to the epsilon amino group of lysine at positions 6, 10, 11, 14, 17, 21, or 22, or to the carboxylic acid group of the side chain of aspartic acid or glutamic acid at position 14. In some embodiments, the PYY analog contains a threonine at a position corresponding to position 32 of hPYY(3-36). In some embodiments, the PYY analog comprises the sequence WLTRQRY at its C-terminus. In some embodiments, the PYY analog has a half-life extending group attached to the epsilon amino group of the lysine at the 7-position.

[0032] In some embodiments, the PYY analog is i) an alanine at a position corresponding to position 4 of hPYY(3-36); ii) a lysine at a position corresponding to position 7 of hPYY(3-36); iii) glutamic acid at a position corresponding to position 9 of hPYY(3-36); iv) a tyrosine at a position corresponding to position 20 of hPYY(3-36); v) the sequence WLTRQRY at its C-terminus Including, The half-life extending group is attached to the epsilon amino group of lysine at position 7, or to the epsilon amino group of lysine at positions 6, 10, 11, 14, 17, 21, or 22, or to the carboxylic acid group of the side chain of aspartic acid or glutamic acid at position 14. In some embodiments, the PYY analog contains an arginine at a position corresponding to position 25 of hPYY(3-36). In some embodiments, the PYY analog has a half-life extending group attached to the epsilon amino group of the lysine at the 7 position. In some embodiments, exactly one half-life extending group is attached to the PYY analogue, and said half-life extending group is attached to the epsilon amino group of the lysine at position 7.

[0033] In some embodiments of the invention, the PYY analog has the formula: R 1 -ZR 2 wherein R 1 is hydrogen, -C(O)C 1-6 Alkyl, -C(O)C6H6, -C(O)C 3-6 Cycloalkyl, -C(O)C 1-6 Alkyl-C 3-6 Cycloalkyl, C 1-6 Alkyl, also C 1-6 Alkyl-C 3-6 is cycloalkyl, R 2 OH or NHR 3 where R 3 is hydrogen or C1-3 is alkyl, Z is an amino acid sequence of Formula I: Ala-X5-X6-Lys-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-Tyr-X 21-X22-X23-X24-Arg-X26-X27-X28-X29-X30-X31-X32-Arg-Gln-Arg-Tyr(I) is a peptide comprising During the ceremony, X5 is selected from the group consisting of Pro and Hyp; X6 is selected from the group consisting of Ala and Glu; X8 is selected from the group consisting of Ala, Ile, Pro, Thr, Val, and Hyp; X9 is selected from the group consisting of Glu, Gly, Gln, and Pro; X10 is selected from the group consisting of Ala and Glu; X11 is selected from the group consisting of Ala, Asp, Glu, and Pro; X12 is selected from the group consisting of Ala, Gly, Ser, Thr, and Val; X13 is selected from the group consisting of Ala, Glu, Ser, Gln, Thr, and Pro; X14 is selected from the group consisting of Ala, Glu, Gly, Pro, and Hyp; X15 is selected from the group consisting of Ala, Glu, and Ser; X16 is selected from the group consisting of Ala, Glu, and Ser; X17 is selected from the group consisting of Ala, Ile, Leu, Thr, and Val; X18 is selected from the group consisting of Glu and Gln; X19 is selected from the group consisting of Ala, Glu, Arg, Lys, and Gln; X21 is selected from the group consisting of Ala, Glu, Gln, and Tyr; X22 is selected from the group consisting of Ile, Ser, Thr, and Val; X23 is selected from the group consisting of Ala, Glu, Ser, and Thr; X24 is selected from the group consisting of Ala, Ile, Leu, Thr, and Val; X26 is selected from the group consisting of Ala, His, and Lys; X27 is selected from the group consisting of Gln and Tyr; X28 is selected from the group consisting of His, Trp, and Tyr; X29 is selected from the group consisting of Asn, Trp, and Tyr; X30 is selected from the group consisting of Ala, His, Trp, and Tyr; X31 is selected from the group consisting of Ala, Ile, Leu, and Thr; X32 is selected from the group consisting of Gln, Leu, and Thr; One to three amino acids among X5, X6, X8 to X19, X21 to X24, and X26 to X32 are absent, The half-life extending group is attached to the epsilon amino group of the lysine at position 7. In a further embodiment, the PYY analogue is according to the previous embodiment, wherein none of X5, X6, X8 to X19, X21 to X24, and X26 to X32 are absent. In a further embodiment, R 1 is -C(O)C 1-4 Alkyl, -C(O)C 3-5 Cycloalkyl, -C(O)C 1-3 Alkyl-C 3-4 Cycloalkyl, C 1-4 Alkyl, or C 1-3 Alkyl-C 3-4 It is cycloalkyl. In a further embodiment, R 1 are -C(O)CH2CH(CH3)2, -C(O)CH2-cyclobutyl, and -C(O)CH2-cyclopropyl. PYY analogs of the present invention having an alanine at position 4 and a lysine at position 7 have generally been found to be soluble at around pH 6 and pH 7.

[0034] Peptide therapeutic agents are usually provided as pharmaceutical liquid formulations in pre-filled ready-to-use injection devices.These peptide formulations for subcutaneous administration have limited application volume.Therefore, good solubility of peptide is a requirement for application in ready-to-use injection devices. A further important aspect is the long-term stability and solubility of the peptide in the liquid formulation. A fundamentally important property for physical stability is inherent solubility (at a given pH value).

[0035] A broad pH range (solubility window) within which peptide therapeutics are reasonably soluble is also desirable, as it allows for greater flexibility in the development of pharmaceutical formulations. This flexibility may be desirable because other factors, such as chemical stability, are also pH-dependent. It is generally believed that peptide formulations at approximately pH 6.0 exhibit reduced oxidation rates (e.g., Cys oxidation, disulfide bridges, and oxidation of Trp residues), deamidation rates, and aspartic acid isomerization rates compared to formulations at pH 7. For example, Bak et al. (A. Bak, D. Leung, SE Barrett, S. Forster, ED Minnihan, AW Leithead, J. Cunningham, N. Toussaint, LS Crocker, The AAPS Journal, Vol. 17, No. 1, 2015, pp. 144-155) state that lowering the pH generally reduces the tendency for oxidation, and suggest maintaining a pH below 7 as a strategy to mitigate the risks associated with oxidation. Therefore, if the chemical stability of peptides containing asparagine, aspartic acid or glutamine, tryptophan, cysteine, or methionine is an issue, it may be desirable to have the option of formulating at approximately pH 6.

[0036] The effectiveness of obesity treatment drugs is limited.However, effectiveness can be improved by combining different therapeutic principles.NPY2 receptor agonists are considered to be promising partners for combination with other weight-reducing treatment drugs.For example, NPY2 receptor agonists show enhanced weight-reducing effectiveness together with GLP-1 receptor agonists (e.g., International Publication Nos. WO2005 / 077072, WO2014 / 178018, WO2018 / 081370) or amylin (e.g., International Publication Nos. WO2006 / 066024, WO2009 / 064298).Natural amylin and many amylin (or calcitonin) analogs contain disulfide bridges. Thus, fixed-dose combinations of PYY analogs and amylin analogs may benefit from the opportunity for formulation at lower pH, where the disulfide bridges of the amylin analog may exhibit improved stability (e.g., due to reduced intramolecular disulfide bond cross-linking reactions). This indicates that the advantage of being able to formulate at a pH below 7 may not only be due to the high stability of the NPY analog, but also that the combination partner may exhibit improved stability (or solubility) at low pH. Therefore, it is highly desirable to identify NPY2 receptor agonists with a broad solubility window to enable co-formulation development with a wide range of partners.

[0037] However, increased solubility should not come at the cost of reduced activity or potency. Surprisingly, alanine at position 4 has been found to increase the solubility of the PYY analogs of the present invention at around pH 6 with no or only a slight negative impact on activity or potency or other important properties (e.g., chemical or physical stability). A long in vivo half-life is also a beneficial property of an agent for reducing food intake in overweight or obese patients. Compounds with a long-acting profile (compared to the very short in vivo half-life of native (human) PYY) that reduces the frequency of administration are desirable. In one aspect, the present invention relates to PYY analogs that are NPY2 receptor agonists. In one aspect, the present invention relates to PYY analogs that exhibit selectivity for NPY receptor subtype Y2 over Y receptor subtypes Y1, Y4, and Y5. In one aspect, the present invention relates to PYY analogs that have an extended half-life, e.g., a half-life longer than that of hPYY(3-36). For example, the PYY analogs of the present invention are suitable for once-weekly administration. Additionally or alternatively, the present invention relates to PYY analogues that have high chemical and / or physical stability, for example, at around pH 6 or pH 7. Further, more specific embodiments are defined below.

[0038] In a further embodiment of the invention, the PYY analog has the formula: R 1 -ZR 2 wherein R 1 is hydrogen, -C(O)C 1-6 Alkyl, -C(O)C6H6, -C(O)C 3-6 Cycloalkyl, -C(O)C 1-6 Alkyl-C 3-6 Cycloalkyl, or C 1-6 Alkyl, or C 1-6 Alkyl-C 3-6 is cycloalkyl, R 2 OH or NHR 3 where R 3 is hydrogen or C 1-3 is alkyl, Z is an amino acid sequence of Formula II: Ala-X5-X6-Lys-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-Tyr-X 21-X22-X23-X24-Arg-X26-Tyr-X28-X29-X30-X31-X32-Arg-Gln-Arg-Tyr(II) and During the ceremony, X5 is selected from the group consisting of Pro and Hyp; X6 is selected from the group consisting of Ala and Glu; X8 is selected from the group consisting of Ala, Pro, and Hyp; X9 is selected from the group consisting of Gln, Gly, Glu, and Pro; X10 is selected from the group consisting of Ala and Glu; X11 is selected from the group consisting of Ala, Asp, Glu, and Pro; X12 is selected from the group consisting of Ala, Gly, and Ser; X13 is selected from the group consisting of Ala, Glu, Ser, Thr, and Pro; X14 is selected from the group consisting of Ala, Glu, Pro, and Hyp; X15 is selected from the group consisting of Ala, Glu, and Ser; X16 is selected from the group consisting of Ala, Glu, and Ser; X17 is selected from the group consisting of Ile, Leu, Thr, and Val; X18 is selected from the group consisting of Gln and Glu; X19 is selected from the group consisting of Ala, Glu, Arg, Lys, and Gln; X21 is selected from the group consisting of Ala, Glu, Gln, and Tyr; X22 is selected from the group consisting of Ile, Ser, Thr, and Val; X23 is selected from the group consisting of Ala, Glu, Ser, and Thr; X24 is selected from the group consisting of Ala, Ile, Leu, Thr, and Val; X26 is selected from the group consisting of Ala, His, and Lys; X28 is selected from the group consisting of Trp and Tyr; X29 is selected from the group consisting of Asn and Tyr; X30 is selected from the group consisting of His, Trp, and Tyr; X31 is selected from the group consisting of Ala, Ile, and Leu; X32 is selected from the group consisting of Gln and Thr; The half-life extending group is attached to the epsilon amino group of the lysine at position 7.

[0039] In some embodiments consistent with the embodiment described immediately above, the half-life extending group comprises a lipophilic substituent X and a linker U, wherein said linker U is attached to an amino acid side chain, said X being attached to U, said lipophilic substituent X being selected from the group consisting of 15-carboxy-pentadecanoyl, 17-carboxy-heptadecanoyl (C18DA), and 19-carboxy-nonadecanoyl, and said linker U being comprised of one, two, or three submoieties (U1, U2, U3), said submoieties being independently selected from the group consisting of Gly, Glu, γ-Glu, ε-Lys, Ser, and OEG.

[0040] In some embodiments of the invention, the PYY analog has the formula: R 1 -ZR 2 wherein R 1 is hydrogen, -C(O)C 1-6 Alkyl, -C(O)C6H6, -C(O)C 3-6 Cycloalkyl, -C(O)C 1-6 Alkyl-C 3-6 Cycloalkyl, or C 1-6 Alkyl, or C 1-6 Alkyl-C 3-6 is cycloalkyl, R 2 OH or NHR 3 where R 3 is hydrogen or C 1-3 is alkyl, Z is an amino acid sequence of Formula III: Ala-Pro-X6-Lys-Pro-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-Tyr-X21-Val-X23-Leu-Arg-His-Tyr-Tyr-Asn-Trp-Leu-Thr-Arg-Gln-Arg-Tyr(III) and During the ceremony, X6 is selected from the group consisting of Ala and Glu; X9 is selected from the group consisting of Glu and Gly; X10 is selected from the group consisting of Ala and Glu; X11 is selected from the group consisting of Ala, Asp, Glu, and Pro; X12 is selected from the group consisting of Ala and Ser; X13 is selected from the group consisting of Ala, Glu, Ser, Thr, and Pro; X14 is selected from the group consisting of Ala, Glu, and Pro; X15 is selected from the group consisting of Ala and Glu; X16 is selected from the group consisting of Ala and Glu; X17 is selected from the group consisting of Ile, Leu, Thr, and Val; X18 is selected from the group consisting of Glu and Gln; X19 is selected from the group consisting of Ala, Glu, Arg, Lys, and Gln; X21 is selected from the group consisting of Glu and Tyr; X23 is selected from the group consisting of Ala, Glu, Ser, and Thr; The half-life extending group is attached to the epsilon amino group of the lysine at position 7. In a further embodiment, the PYY analog is a compound according to Formulas I-III, wherein at least two amino acids from X6, X10, X11, X13, and X23 are selected from the group consisting of Asp and Glu. In a further embodiment, the PYY analogue is a compound according to any of the preceding embodiments, wherein only one of X6, X10, and X15 is Ala.

[0041] In a further embodiment of the invention, the PYY analog has the formula: R 1 -ZR 2 wherein R 1 is hydrogen, -C(O)C 1-6 Alkyl, -C(O)C6H6, -C(O)C 3-6 Cycloalkyl, -C(O)C 1-6 Alkyl-C 3-6 Cycloalkyl, or C 1-6 Alkyl, or C 1-6 Alkyl-C 3-6 is cycloalkyl, R 2 OH or NHR 3 where R 3 is hydrogen or C 1-3 is alkyl, Z is an amino acid sequence of Formula IV: Ala-Pro-X6-Lys-Pro-Glu-X10-X11-Ala-X13-X14-Glu-Glu-X17-Gln-X19-Tyr-Tyr-Val-X23-Leu-Arg-His-Tyr-Tyr-Asn-Trp-Leu-Thr-Arg-Gln-Arg-Tyr(IV) and During the ceremony, X6 is selected from the group consisting of Ala and Glu; X10 is selected from the group consisting of Ala and Glu; X11 is selected from the group consisting of Ala, Asp, and Glu; X13 is selected from the group consisting of Ala, Glu, Ser, and Thr; X14 is selected from the group consisting of Ala, Pro, and Hyp; X17 is selected from the group consisting of Ile and Leu; X19 is selected from the group consisting of Arg, Lys, and Gln; X23 is selected from the group consisting of Ala, Glu, and Ser; The half-life extending group is attached to the epsilon amino group of the lysine at position 7. In a further embodiment, the PYY analog is a compound according to formula IV, wherein at least two amino acids from X6, X10, X11, X13, and X23 are selected from Asp or Glu. In a further embodiment, the PYY analog is a compound according to formula IV, wherein only one of X6 and X10 is Ala. In a further embodiment, the PYY analogue is a compound according to any of the preceding embodiments, wherein X6 is Ala. In a further embodiment, R 1 is hydrogen, -C(O)C 1-6 Alkyl, -C(O)C 3-6 Cycloalkyl, or C 1-6 It is alkyl. In a further embodiment, R 1 is hydrogen or -C(O)C 1-6 It is alkyl. In a further embodiment, R 1 is hydrogen or -C(O)C 1-4 It is alkyl. In more specific embodiments, R 1 is -C(O)CHCH(CH). In more specific embodiments, R 2 is NH2.

[0042] In some embodiments of the invention, the PYY analog has the formula: R 1 -ZR 2 wherein R 1 and R 2 is defined as one of the definitions above, Z is an amino acid sequence selected from Table 1;

[0043] [Table 1-1]

[0044] [Table 1-2]

[0045] [Table 1-3]

[0046] [Table 1-4]

[0047] [Table 1-5]

[0048] [Table 1-6]

[0049] The half-life extending group is attached to the epsilon amino group of lysine at position 7, or to the epsilon amino group of lysine at positions 6, 10, 11, 14, 17, 21, or 22, or to the carboxylic acid group of the side chain of aspartic acid or glutamic acid at position 14.

[0050] In one embodiment of the invention, the PYY analog has the formula: R 1 -ZR 2 wherein R 1 and R 2 is as defined above, Z is an amino acid sequence selected from Table 1; The half-life extending group is attached to the epsilon amino group of the lysine at position 7 and consists of a lipophilic substituent X and a linker U, wherein the linker U is attached to an amino acid side chain, and the X is attached to U, and the linker U consists of one, two, or three submoieties (U1, U2, U3). In some embodiments, the lipophilic substituent X is selected from the group consisting of 15-carboxy-pentadecanoyl, 17-carboxy-heptadecanoyl (C18DA), and 19-carboxy-nonadecanoyl.

[0051] In some embodiments, the linker U is composed of one, two, or three submoieties (U) independently selected from the group consisting of Gly, Glu, γ-Glu, ε-Lys, Ser, and OEG, or independently selected from the group consisting of γ-Glu and OEG. 1 , U 2 , U 3 ) consists of In certain embodiments, the linker U is selected from the group consisting of γ-Glu, γ-Glu-γ-Glu, γ-Glu-OEG, OEG-OEG, γ-Glu-γ-Glu-OEG, γ-Glu-OEG-OEG.

[0052] In a specific embodiment, the half-life extending group is C18DA-γ-Glu-OEG-OEG-, i.e., [ka] is. In some embodiments of the present invention, the PYY analog is a compound selected from the group consisting of Compound 1 to Compound 244, as defined below. In some embodiments, the PYY analog has up to 15 amino acid modifications compared to hPYY(3-36).

[0053] In some embodiments, the PYY analog has up to 14 amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has up to 13 amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has up to 12 amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has up to 11 amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has 7 to 15 (i.e., 7, 8, 9, 10, 11, 12, 13, 14, or 15) amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has 8 to 14 (ie, 8, 9, 10, 11, 12, 13, or 14) amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has between 5 and 13 (i.e., 5, 6, 7, 8, 9, 10, 11, 12, or 13) amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has 7 to 13 (ie, 7, 8, 9, 10, 11, 12, or 13) amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has 8 to 13 (ie, 8, 9, 10, 11, 12, or 13) amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has 9 to 13 (ie, 9, 10, 11, 12, or 13) amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has 10 to 13 (ie, 10, 11, 12, or 13) amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has 8 to 12 (ie, 8, 9, 10, 11, or 12) amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has 9 to 12 (ie, 9, 10, 11, or 12) amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has 10 to 12 (ie, 10, 11, or 12) amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has 9 to 11 (ie, 9, 10, or 11) amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analog has 11 to 12 (ie, 11 or 12) amino acid modifications compared to hPYY(3-36). In some embodiments, the PYY analogue or compound of the above embodiments is in the form of a salt, preferably a pharmaceutically acceptable salt. The PYY analogs of the present invention are capable of binding to the human NPY2 receptor (hNPY2-R). Binding to biological receptors can be measured by suitable assays known in the art. For example, binding of PYY analogs to NPY2 receptors can be assessed by a radioligand binding competition assay, for example, as described in Example 1 below. In some embodiments of the compounds of the present invention, the binding affinity (Ki) for the hNPY2 receptor is less than 100 nM (eg, 0.01 to 100 nM). In some embodiments of the compounds of the present invention, the binding affinity (Ki) for the hNPY2 receptor is less than 50 nM (eg, 0.01 to 50 nM). In some embodiments of the compounds of the present invention, the binding affinity (Ki) for the hNPY2 receptor is less than 10 nM (eg, 0.01 to 10 nM). In some embodiments of the compounds of the present invention, the binding affinity (Ki) for the hNPY2 receptor is less than 5 nM (eg, 0.01 to 5 nM). In some embodiments of the compounds of the present invention, the binding affinity (Ki) for the hNPY2 receptor is less than 2 nM (eg, 0.01 to 2 nM). The PYY analogs of the present invention activate the human NPY2 receptor, ie, are NPY2 agonists.

[0054] Generally, it is preferred to use the biological assay that measures the intracellular signal transduction caused by the binding of compound to the relevant receptor.The activation of NPY2 receptor by the compound of the present invention (acting as the agonist of receptor) reduces the cAMP concentration, which affects intracellular signal transduction pathway.Therefore, the reduction of cAMP in the cell that expresses receptor or any other suitable parameter can be used to monitor the agonist activity of receptor.Those skilled in the art will be aware of suitable assay formats, and examples thereof are described below.

[0055] EC 50 The EC value can be used as a numerical measure of agonist potency at a given receptor. 50 The value is a measure of the concentration of compound required to achieve half of the compound's maximal activity in a particular assay, such as the assay described in Example 2 below. In some embodiments of the compounds of the present invention, the EC 50 is less than 100 nM (for example, 0.001 to 100 nM). In some embodiments of the compounds of the present invention, the EC 50 is less than 50 nM (for example, 0.001 to 50 nM). In some embodiments of the compounds of the present invention, the EC 50 is less than 10 nM (for example, 0.001 to 10 nM). In some embodiments of the compounds of the present invention, the EC 50 is less than 5 nM (for example, 0.001 to 5 nM). In some embodiments of the compounds of the present invention, the EC 50 is less than 2 nM (for example, 0.001 to 2 nM).

[0056] As mentioned above, the PYY analogs or compounds of the present invention are generally soluble at around pH 7 and 6. There are several techniques known to those skilled in the art for determining solubility. One such experiment is described below in Example 3. When specific solubility in mg / ml is provided herein, it refers to the solubility determination in Example 3. In some embodiments, the solubility of a PYY analog or compound of the invention is greater than 1.0 mg / ml at around pH 6 (eg, pH 6.1±0.2). In some embodiments, the solubility of a PYY analog or compound of the invention is greater than 3.0 mg / ml at around pH 6 (eg, pH 6.1±0.2). In some embodiments, the solubility of a PYY analog or compound of the invention is greater than 5.0 mg / ml at around pH 6 (eg, pH 6.1±0.2). In some embodiments, the solubility of a PYY analog or compound of the invention is 7.0 mg / ml or greater at around pH 6 (eg, pH 6.1±0.2). In some embodiments, the solubility of a PYY analog or compound of the invention is 8.0 mg / ml or greater at around pH 6 (eg, pH 6.1±0.2). In some embodiments, the solubility of a PYY analog or compound of the invention is greater than 1.0 mg / ml at around pH 7 (eg, pH 6.8±0.2). In some embodiments, the solubility of a PYY analog or compound of the invention is greater than 5.0 mg / ml at around pH 7 (eg, pH 6.8±0.2). In some embodiments, the solubility of a PYY analog or compound of the invention is greater than 7.0 mg / ml at around pH 7 (eg, pH 6.8±0.2). In some embodiments, the solubility of a PYY analog or compound of the invention is 8.0 mg / ml or greater at around pH 7 (eg, pH 6.8±0.2). In some embodiments, the solubility of a PYY analog or compound of the invention is greater than 1.0 mg / ml at around pH 6 (eg, pH 6.1±0.2) and around pH 7 (eg, pH 6.8±0.2). In some embodiments, the solubility of a PYY analog or compound of the invention is greater than 3.0 mg / ml at around pH 6 (eg, pH 6.1±0.2) and around pH 7 (eg, pH 6.8±0.2). In some embodiments, the solubility of a PYY analog or compound of the invention is greater than 5.0 mg / ml at around pH 6 (eg, pH 6.1±0.2) and around pH 7 (eg, pH 6.8±0.2). In some embodiments, the solubility of a PYY analog or compound of the invention is greater than 6.0 mg / ml at around pH 6 (eg, pH 6.1±0.2) and around pH 7 (eg, pH 6.8±0.2).

[0057] In some embodiments, the PYY analogs or compounds of the present invention have favorable pharmacokinetic properties. In this regard, in some embodiments of the present invention, the in vivo half-life of the PYY analogs or compounds is at least 3 hours in mice (NMRI mice, see measurements described in Example 5). In some embodiments, the in vivo half-life is at least 5 hours in mice. In some embodiments, the in vivo half-life is at least 7 hours in mice. In some embodiments, the in vivo half-life is at least 10 hours in mice. The present invention further provides a composition comprising the PYY analogue described above. The composition may be a pharmaceutical composition, and may comprise a pharmaceutically acceptable carrier, excipient, or vehicle. The present invention further provides methods for the synthesis of the above-mentioned PYY analogs, which may comprise the steps of synthesizing the peptide by solid-phase or liquid-phase methods, and optionally isolating and / or purifying the final product.

[0058] Treatment method The present invention is directed to PYY analogs or compounds as described in the above embodiments, which are useful in the prevention and / or treatment of diseases and / or conditions associated with or modulated by NPY2 receptor activity, including, but not limited to, the treatment and / or prevention of obesity and various obesity-related conditions, diseases, or comorbidities, such as type 2 diabetes and NASH (non-alcoholic steatohepatitis).

[0059] The compounds described herein are particularly useful for preventing weight gain or promoting weight loss. "Preventing" refers to prevention or reduction compared to the absence of treatment, and does not necessarily mean complete cessation of weight gain. Peptides can reduce food intake and / or increase energy expenditure, have beneficial effects on glucose regulation and / or circulating cholesterol levels, reduce circulating LDL levels, and increase the HDL / LDL ratio. Thus, the compounds of the present invention can be used for the direct or indirect treatment of any condition caused by or characterized by excess weight, such as the treatment and / or prevention of obesity, morbid obesity, obesity-related inflammation, obesity-related gallbladder disease, and obesity-related sleep apnea. They may also be used to prevent or treat conditions such as obesity-related co-comorbidities caused by or characterized by inadequate glucose control or dyslipidemia (e.g., elevated LDL levels or reduced HDL / LDL ratios), type 2 diabetes, metabolic syndrome, hypertension, atherogenic dyslipidemia, and cardiovascular disease, such as atherosclerosis, coronary heart disease, peripheral artery disease, stroke, or microvascular disease, and cancer. Their effects on these conditions may be the result of or associated with their effects on body weight, or may be independent thereof.

[0060] As described above, the PYY analogs or compounds according to the above embodiments are useful for reducing food intake, promoting weight loss, and preventing or reducing weight gain. As a result, they can be used to treat various conditions, diseases, or disorders in subjects, including, but not limited to, obesity and various obesity-related conditions, diseases, or comorbidities, such as type 2 diabetes, hypertension, dyslipidemia, sleep apnea, cardiovascular disease, fatty liver, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and cancer. The subject may suffer from obesity accompanied by at least one weight-related comorbid condition, such as type 2 diabetes, hypertension, dyslipidemia, sleep apnea, cardiovascular disease, fatty liver, NAFLD, and NASH. It will be appreciated, therefore, that PYY analogs can be administered to subjects suffering from conditions characterized by inadequate appetite control or otherwise overeating, such as binge eating disorder and Prader-Willi syndrome. It will be apparent that the present analogues may be used to treat a combination of the conditions described.

[0061] Thus, the present invention provides PYY analogs for use in methods of medical treatment, e.g., for treating, preventing, or reducing weight gain, promoting weight loss, and / or reducing excess weight. Treatment can be achieved, for example, by controlling appetite, diet, food intake, calorie intake, and / or energy expenditure.

[0062] The present invention also provides the PYY analogues of the present invention for use in methods for treating obesity and related diseases, disorders and health conditions, including but not limited to morbid obesity, pre-surgical obesity, obesity-related inflammation, obesity-related gallbladder disease, and obesity-related sleep apnea and respiratory problems, cartilage degeneration, osteoarthritis, and obesity or excess weight-related reproductive health complications, such as infertility.The subject may suffer from obesity accompanied by at least one weight-related comorbidity, such as type 2 diabetes, hypertension, dyslipidemia, sleep apnea, cardiovascular disease, cancer, fatty liver, NAFLD and NASH. The present invention also provides a PYY analogue of the present invention for use in a method for the prevention or treatment of the above-mentioned conditions. Thus, the present invention relates to a PYY analogue or compound according to the above-mentioned embodiments for use as a medicament. Furthermore, the present invention relates to the use of a PYY analogue or compound according to the above-mentioned embodiments for the treatment and / or prevention of diseases and / or conditions associated with or modulated by NPY2 receptor activation.

[0063] Furthermore, the present invention relates to the use of a PYY analogue or compound according to the above-mentioned embodiments for the treatment and / or prevention of obesity and various obesity-related conditions, diseases, or complications, such as type 2 diabetes and NASH (non-alcoholic steatohepatitis), as well as others mentioned above. In a further aspect, the present invention relates to the use of a PYY analogue or compound according to the above-mentioned embodiments for the preparation of a medicament for the treatment and / or prevention of the above-mentioned diseases and conditions. In a further aspect, the present invention relates to a method for the treatment or prevention of the above-mentioned diseases and conditions, comprising administering to a human an effective amount of a PYY analogue or compound according to the above-mentioned embodiments. The weekly applied dose range of the compounds of general formula 1 is usually 0.01 to 100 mg (subcutaneous administration) for humans.

[0064] The actual pharmaceutically effective amount or therapeutic dosage will generally depend on factors known to those skilled in the art, such as the age and weight of the patient, the route of administration, and the severity of the disease. In any case, the compound will be administered in a dosage and manner that allows for the delivery of a pharmaceutically effective amount based on the patient's unique condition.

[0065] Combination therapy The PYY analogs of the present invention can be administered as part of a combination therapy with another active agent for treating the disease or disorder in question, such as an anti-obesity agent, an anti-diabetic agent, an agent for treating metabolic syndrome, an anti-dyslipidemic agent, an anti-hypertensive agent, a proton pump inhibitor, or an anti-inflammatory agent. In such cases, the two active agents can be provided together or separately, for example, as components of the same pharmaceutical composition or formulation, or as separate formulations.

[0066] Therefore, the peptides of the present invention can be used in combination with known types of anti-obesity agents, such as GIP or GLP-1 receptor agonists (including GLP-1 or GLP-1 analogs), exendin-4 or exendin-4 analogs, any other GLP-1 receptor agonists, such as liraglutide (Saxenda™), semaglutide, dulaglutide, albiglutide, MK-8521, or glucagon-GLP-1 dual agonists (e.g., HM-12525). , SAR-425899, MEDI-0382, NN-9277, or International Publication Nos. WO2008 / 101017, WO2008 / 152403, WO2010 / 070252, WO2010 / 070253, WO2010 / 070255, WO2010 / 070251, WO2011 / 006497, WO2011 / 160630, WO2011 / 1 60633, WO2013 / 092703, WO2014 / 041195, WO2015 / 055801, WO2015 / 055802, WO2016 / 166289), oxyntomodulin or oxyntomodulin analogs (e.g., TT-401), or GLP-1 / GIP dual agonists (e.g., tirzepatide, or those described in International Publication No. WO WO2013 / 164483), or a GLP-1 / GIP / glucagon triple agonist (e.g., NN-9423, or those described in International Publication Nos. WO2015 / 067716, WO2016 / 198624, WO2017 / 116204, WO2017 / 116205, WO2018 / 100134, WO2018 / 100135).

[0067] The anti-obesity agent can be amylin or an amylin analog, such as pramlintide, NN-9838, or an amylin (or calcitonin) analog disclosed in International Publication Nos. WO2012 / 168430, WO2012 / 168431, WO2012 / 168432, WO2015 / 040182, WO2015 / 071229, WO2016 / 146739, WO2018 / 046719, or WO2018 / 172390.

[0068] Alternatively, the anti-obesity agent can be Orlistat™, Sibutramine™, phentermine, melanin-concentrating hormone receptor 1 antagonists, CCK, leptin analogs, GOAT inhibitors, ghrelin receptor antagonists, additional neuropeptide Y (NPY) analogs, NPY4 receptor agonists, NPY5 receptor antagonists, cannabinoid receptor 1 antagonists, beta-3 agonists, lipase inhibitors, human islet precursor (proIslet) peptide (HIP), melanocortin receptor 4 agonists, and analogs thereof.

[0069] Furthermore, the peptides of the present invention may be used in combination with metformin, sulfonylureas, glinides, DPP-IV inhibitors, glitazones, GLP-1 receptor agonists (including GLP-1 or GLP-1 analogs), exendin-4 or exendin-4 analogs, any other GLP-1 receptor agonist, such as liraglutide (Victoza™), semaglutide, dulaglutide, albiglutide, MK-8521, or are glucagon-GLP-1 dual agonists (e.g., HM-12525, SAR-425899, MEDI-0382, NN-9277, or those disclosed in International Publication Nos. WO2008 / 101017, WO2008 / 152403, WO2010 / 070252, WO2010 / 070253, WO2010 / 070255, WO2010 / 070251, WO2011 / 006497, and those described in WO2011 / 160630, WO2011 / 160633, WO2013 / 092703, WO2014 / 041195, WO2015 / 055801, WO2015 / 055802, and WO2016 / 166289), oxyntomodulin or an oxyntomodulin analog (e.g., TT-401), or an SGLT2 inhibitor (i.e., sodium - May have some benefit when administered in combination with known types of antidiabetic agents, including but not limited to glucose transport inhibitors, such as gliflozins (e.g., empagliflozin, canagliflozin, dapagliflozin, or ipragliflozin), GPR40 agonists (FFAR1 / FFA1 agonists, e.g., fasiglifam), or insulin or insulin analogs. Examples of suitable insulin analogs include, but are not limited to, Lantus™, Novorapid™, Humalog™, Novomix™, Actraphane™, HM, Levemir™, Degludec™, and Apidra™.Other relevant antidiabetic agents in this regard include GLP-1 receptor agonists such as exenatide (Byetta™ and Bydureon™ exendin-4), and Byetta LAR™, and lixisenatide (Lyxumia™).

[0070] According to a more specific embodiment, the PYY analogues of the present invention comprise: a GLP-1 receptor agonist selected from the group consisting of liraglutide, semaglutide, dulaglutide, and albiglutide, or the glucagon-GLP-1 dual agonists described in WO2011 / 006497, WO2014 / 041195, WO2015 / 055801, WO2015 / 055802, WO2016 / 166289, an amylin receptor agonist selected from the group consisting of pramlintide or an amylin analogue disclosed in WO2012 / 168430, WO2012 / 168431, WO2012 / 168432, WO2015 / 040182, WO2016 / 146739 or WO2018 / 046719, It is administered as part of a combination therapy with

[0071] The peptides of the present invention may further be used in combination with drugs targeting cardiovascular diseases, such as drugs for treating hypertension, dyslipidemia, inflammation, and platelet function. Drugs for treating hypertension may be selected from the group including, but not limited to, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, diuretics, beta-blockers, or calcium channel blockers. The peptides of the present invention may still further be used in combination with known types of anti-dyslipidemic agents, including, but not limited to, statins, fibrates, niacin, PSCK9 (proprotein convertase subtilisin / kexin type 9) inhibitors, or cholesterol absorption inhibitors.

[0072] The peptides of the present invention may also be used in combination with known types of proton pump inhibitors (i.e., H), including, but not limited to, benzimidazole- or imidazopyridine-derivative drugs, such as Omeprazole™, Lansoprazole™, Dexlansoprazole™, Esomeprazole™, Pantoprazole™, Rabeprazole™, Zolpidem™, Alpidem™, Saripidem™, or Necopidem™. + / K + -ATPase inhibitors).

[0073] In addition, for anti-inflammatory treatment, the peptides of the present invention steroids and corticosteroids, such as beclomethasone, methylprednisolone, betamethasone, prednisone, dexamethasone, and hydrocortisone; Nonsteroidal anti-inflammatory drugs (NSAIDs), such as propionic acid derivatives (e.g., alminoprofen, benoxaprofen, bucloxic acid, carprofen, fenbufen, fenoprofen, fluprofen, flurbiprofen, ibuprofen, indoprofen, ketoprofen, miroprofen, naproxen, oxaprozin, pirprofen, pranoprofen, suprofen, tiaprofenic acid, and tioxaprofen), acetic acid derivatives (e.g., indomethacin, acemetacin, alclofenac, clidanac, diclofenac, fenclofenac, fenclozic acid, fentiazac, furofenac, ibufenac, isoxepac, oxipinac, sulindac, tiopinac), , tolmetin, zidometacin, and zomepirac), fenamic acid derivatives (e.g., flufenamic acid, meclofenamic acid, mefenamic acid, niflumic acid, and tolfenamic acid), biphenylcarboxylic acid derivatives (e.g., diflunisal and flufenisal), oxicams (e.g., isoxicam, piroxicam, sudoxicam, and tenoxicam), salicylates (e.g., acetylsalicylic acid and sulfasalazine), and pyrazolones (e.g., apazone, bezupiperylone, feprazone, mofebutazone, oxyphenbutazone, and phenylbutazone), COX II inhibitors such as rofecoxib and celecoxib, preparations of interferon beta (e.g., interferon beta-1a or interferon beta-1b), and certain other compounds, such as 5-aminosalicylic acid, and prodrugs and pharmaceutically acceptable salts thereof.

[0074] preparation General Procedure for Solid Phase Synthesis of Peptides All peptides were synthesized by standard Fmoc-based solid-phase peptide chemistry on Tentagel S RAM resin (loading 0.23–0.25 mmol / g, bead size 90 μm) supplied by Iris Biotech GmbH or Rapp Polymere GmbH.

[0075] The following protected amino acids were used: Fmoc-Ala-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Asp(tBu)-OH, F moc-Gln(Trt)-OH, Fmoc-Glu(tBu)-OH, Fmoc-Glu-OtBu, Fmoc-Gly-OH, Fmoc-His(Trt)-OH, Fmo c-Ile-OH, Fmoc-Leu-OH, Fmoc-Lys(Boc)-OH, Fmoc-Lys(Dde)-OH, Fmoc-Phe-OH, Fmoc-Pro-OH, Fmoc-Ser(tBu)-OH, Fmoc-Thr(tBu)-OH, Fmoc-Trp(Boc)-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Val-OH. Unless otherwise indicated, L-configuration amino acid building blocks were utilized. Modular half-life extenders were constructed by solid phase peptide synthesis (SPPS) using protected building blocks such as, but not limited to, 18-(tert-butoxy)-18-oxooctadecanoic acid (C18DA(tBu)), 2-[2-[2-[[2-[2-[2-(9H-fluoren-9-ylmethoxycarbonylamino)ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetic acid (Fmoc-OEG-OEG-OH), 2-[2-[2-(9H-fluoren-9-ylmethoxycarbonylamino)ethoxy]ethoxy]acetic acid (Fmoc-OEG-OH), and Fmoc-Glu-OtBu.

[0076] Amino acids, Fmoc-Glu-OtBu, Oxyma, and DIC were purchased from standard suppliers, e.g., Bachem, Novabiochem, ABCR, Iris Biotech GmbH, Sigma-Aldrich. 18-(Tert-butoxy)-18-oxooctadecanoic acid (C18DA(tBu)) was provided by Cool Pharm Ltd. or AstraTech, 2-[2-[2-[[2-[2-[2-(9H-Fluoren-9-ylmethoxycarbonyl-amino)ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetic acid (Fmoc-OEG-OEG-OH) was provided by ABCR GmbH & CO. KG or Iris Biotech GmbH, 2-[2-[2-(9H-Fluoren-9-ylmethoxycarbonylamino)ethoxy]ethoxy]acetic acid (Fmoc-OEG-OH) was provided by Combi Blocks Inc., Iris Biotech GmbH, or Hangzhou APIChem Technology Co., Ltd., and 3-methylbutanoic acid was provided by Sigma-Aldrich GmbH. Assembly of the peptides starting from the C-terminus was achieved by stepwise chain elongation towards the N-terminus according to the respective sequences until the N-terminal capping group was reached. Assembly of the half-life extender was carried out after deprotection of the branched amino acid side chains, e.g., Lys(Dde). The PYY analogs were obtained as TFA salts by cleavage / deprotection or HPLC purification. The trifluoroacetate was exchanged by standard procedures, such as resin-ion exchange procedures, as disclosed in, for example, Roux, St. et al. J. Pept. Sci. 2008; 14: 354-359.

[0077] Synthesis method 1 (S01) Peptides were synthesized by microwave-assisted solid-phase peptide synthesis (SPPS) on a CEM Liberty Blue Peptide Synthesizer on a 0.25 mmol scale on Tentagel S RAM resin using the Fmoc strategy.

[0078] Standard amino acid coupling was performed using 4 equivalents of a suitable protected amino acid in DMF (0.2 mol / L, 5 ml), 4 equivalents of Oxyma in DMF (1 mol / L, 1 ml), and 8 equivalents of DIC in DMF (1 mol / L, 2 ml) at 90°C for 4 min. Fmoc-Arg(Pbf)-OH was coupled twice for 4 min at 90°C, Fmoc-His(Trt)-OH was coupled twice for 12 min at 50°C, and Fmoc-Glu-OtBu was coupled four times for 12 min at 50°C. Fmoc-OEG-OH, Fmoc-OEG-OEG-OH, and C18DA(tBu) were coupled twice for 4 min at 90°C. N-terminal capping was achieved by coupling 3-methylbutanoic acid three times for 4 min at 90°C. N α Fmoc deprotection was carried out using 20% ​​piperidine / DMF (10 ml) for 1 minute at 90° C. Deprotection of the Lys(Dde) group was carried out twice using 5% hydrazine hydrate (10 ml) in DMF for 3 minutes at 90° C.

[0079] The crude product was washed with DCM on the resin and dried before cleavage. Cleavage from the resin and deprotection were carried out with a mixture of 95% TFA / water (10 ml) and triisopropylsilane (250 μl) at 42° C. for 40 min. The crude peptide was precipitated with cold diethyl ether, dissolved in 50% acetonitrile / water, and purified by preparative HPLC (P01). Synthesis method 2 (S02) Peptides were synthesized by SPPS on a MultiSynTech SYRO II on a 0.2 mmol scale. Standard coupling of amino acids was achieved using 4 equivalents of a suitable protected amino acid dissolved in 0.5 mol / L Oxyma-DMF solution (0.5 mol / L, 1.6 ml) and 4.5 equivalents of DIC in DMF (0.5 mol / L, 1.8 ml). Fmoc-Phe-OH was dissolved in 0.5 mol / L Oxyma-NMP, and 4 equivalents were used for the coupling (0.5 mol / L, 1.6 ml).

[0080] The coupling time for the first 15 amino acids, starting from the C-terminus, was 2 hours at room temperature. Subsequent couplings were achieved by double coupling (2 times for 2 hours at room temperature). Capping of the N-terminus was achieved by coupling with 3-methylbutanoic acid (2 times for 2 hours at room temperature). Deprotection of the Lys(Dde) group was selectively performed using 5% hydrazine in DMF (5 times for 5 minutes at room temperature, 4 ml), followed by coupling with 4 equivalents of Fmoc-OEG-OEG-OH (3 times for 2 hours at room temperature), 4 equivalents of Fmoc-Glu-OtBu, and 4 equivalents of C18DA(tBu) (2 times for 2 hours at room temperature). N α Fmoc deprotection was carried out using 40% piperidine in NMP (4 ml) for 3 minutes followed by 20% piperidine in NMP (4 ml) for 15 minutes at room temperature.

[0081] The peptide was cleaved from the resin and the side chains deprotected by adding 15 ml of 95:2:1:2 TFA:DODT:TES:water for 4 hours at room temperature or 45 minutes at 45° C. The peptide was precipitated with cold diethyl ether, dissolved in acetonitrile / water, and purified by preparative HPLC (P02). Synthesis method 3 (S03) Peptides were synthesized on a 0.2 mmol scale using microwave-assisted SPPS on a Biotage Alstra Synthesizer. Standard coupling of amino acids was achieved using 5 equivalents of a suitable protected amino acid dissolved in 0.5 mol / l Oxyma-DMF solution (0.5 mol / l, 2 ml) and 5 equivalents of DIC in DMF (0.5 mol / l, 2 ml). Coupling of the first 15 amino acids starting from the C-terminus was achieved by heating at 75°C for 5 minutes. Subsequent couplings were achieved by double coupling (75°C for 5 minutes twice). N α Fmoc deprotection was carried out using 20% ​​piperidine in DMF for 30 seconds, followed by 20% piperidine at 75° C. for 3 minutes.

[0082] Special conditions were used for the following: coupling of Fmoc-His(Trt)-OH (2 times 12 min at 50°C) and subsequent Fmoc deprotection at room temperature (3 min with 20% piperidine in DMF, followed by 10 min with 20% piperidine in DMF); coupling of Fmoc-Glu-OtBu (2 times 6 min at 75°C) and Fmoc-Arg(Pbf)-OH (2 times 5 min at 75°C); Fmoc-As Coupling of p(tBu)-OH followed by Fmoc deprotection at room temperature (20% piperidine in DMF for 3 min, followed by 20% piperidine in DMF for 10 min); Dde deprotection with 5% hydrazine in DMF (5 times for 5 min at room temperature); coupling of 4 equivalents of Fmoc-OEG-OEG-OH (3 times for 10 min at 75 °C) and 2.5 equivalents of C18DA(tBu) (2 times for 10 min at 75 °C). Cleavage from the resin and side-chain deprotection were carried out by adding 8 ml of 95:2:1:2 TFA:DODT:TES:water for 4 h at room temperature or 45 min at 45° C. The crude peptide was precipitated with cold diethyl ether, dissolved in 50% acetonitrile / water, and purified by preparative HPLC (P02).

[0083] Purification method 1 (P01) The crude peptide was purified by reverse-phase chromatography using an Agilent preparative HPLC-MS system equipped with a G1361A preparative pump, a G1315B diode array detector, a G1956B mass spectrometer, and a CTC PAL IFC fraction collector. A Waters XSelect CSH Prep C18 column (130 Å, 5 μm, OBD, 30 mm × 150 mm) served as the stationary phase. The mobile phase consisted of a gradient of Buffer A (0.1% TFA in HO) and Buffer B (0.1% TFA in ACN, gradient: 20–42% over 44 min) at a flow rate of 50 ml / min at 40°C. Relevant fractions were pooled and lyophilized. The final product was characterized by HPLC-MS analysis (A01).

[0084] Purification method 2 (P02) The crude peptide was purified by reverse-phase HPLC using a Waters preparative HPLC with a C8 column (Reprosil Gold 200 Å, 5 μm, 40 mm × 250 mm), a preparative pump (Waters 2545), a UV / VIS detector (Waters 2489), and a Waters fraction collector III. The mobile phase consisted of a gradient of buffer A (0.1% TFA in HO) and buffer B (0.1% TFA in ACN, gradient: 35–45% over 10 min) at room temperature, with a flow rate of 50 ml / min. Relevant fractions were analyzed, pooled, and lyophilized. The final product was characterized by UPLC-MS analysis (A02).

[0085] Analysis method 1 (A01) The purity and mass of the peptides were determined by HPLC-MS analysis on a Kinetex C8 column (Phenomenex, 100 Å, 2.6 μm, 4.6 mm × 150 mm) using a Waters Acquity HPLC system equipped with a 3100 Mass Detector. The analysis was performed by gradient elution with Buffer A (0.3% TFA in HO) and Buffer B (0.24% TFA in ACN) at a temperature of 40°C. The gradient and flow rate details are summarized in the table below. Retention times and masses were recorded.

[0086] TIFF0007821393000009.tif73161

[0087] Analysis method 2 (A02) UPLC-MS analysis was performed in a Waters Acquity Class H using a Waters Acquity UPLC C18 column (Peptide CSH™ 130 Å, 1.7 μm, 2.1 mm × 100 mm) connected to an SQ Detector 2 (ESI, Waters) and a gradient run of Buffer C (0.3% TFA in HO) and Buffer D (10% HO + 0.3% TFA in ACN; 38–48% D over 14 min).

[0088] List of abbreviations ACN: acetonitrile Boc: tert-butoxycarbonyl C18DA(tBu): 18-(tert-butoxy)-18-oxooctadecanoic acid DPBS: Dulbecco's phosphate buffered saline DCM: dichloromethane DIC: diisopropylcarbodiimide DIPEA: Diisopropylethylamine Dde: (4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl DMF: N,N-dimethylformamide DODT: 3,6-dioxa-1,8-octanedithiol Fmoc: 9H-fluoren-9-ylmethoxycarbonyl Fmoc-OEG-OH: 2-[2-[2-(9H-fluoren-9-ylmethoxycarbonylamino)ethoxy]ethoxy]acetic acid Fmoc-OEG-OEG-OH: 2-[2-[2-[[2-[2-[2-(9H-fluoren-9-ylmethoxycarbonyl-amino)ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetic acid HTRF: Homogeneous Time-Resolved Fluorescence IBMX: 3-isobutyl-1-methylxanthine iVal: 3-methylbutanoyl (isovalerianoyl) MRT: Average residence time NMP: 1-methyl-pyrrolidin-2-one Oxyma: 2-cyano-2-(hydroxyimino)acetic acid ethyl ester OEG: 2-[2-(2-aminoethoxy)ethoxy]acetic acid Pbf: 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl Rt: retention time RT: room temperature SPPS: Solid Phase Peptide Synthesis tBu: tert-butyl Trt: Trityl TES: Triethylsilane TFA: Trifluoroacetic acid The following compounds were synthesized: All compounds were obtained as TFA salts.

[0089] compound 1 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13Q,18Q,19E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAQPEELQEYYVSLRHYYNWLTRQRY-NH2

[0090] [ka] Molecular weight (calculated): 5001.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.17min, m / 3:1668.0, m / 4:-, m / 5:-

[0091] compound 2 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,5Hyp,7K,9E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-AHypEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5003.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.29min, m / 3:1668.0, m / 4:-, m / 5:-

[0092] compound 3 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11E, 15A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPAELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4943.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.86min, m / 3:-, m / 4:1237.0, m / 5:-

[0093] compound 4 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22V,28Y,30W,31L,32Q]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSLRHYYNWLQRQRY-NH2 Molecular weight (calculated): 5014.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.31min, m / 3:1672.0, m / 4:-, m / 5:-

[0094] compound 5 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11E, 12V, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEVSPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5029.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.02min, m / 3:-, m / 4:1258.0, m / 5:-

[0095] compound 6 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11E, 18Q, 22V, 24A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELQRYYVSARHYYNWLTRQRY-NH2 Molecular weight (calculated): 4959.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.32min, m / 3:-, m / 4:1241.0, m / 5:-

[0096] compound 7 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,19A,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQAYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4902.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.00min, m / 3:-, m / 4:1226.0, m / 5:-

[0097] compound 8 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,14E,18Q,19Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASEEELQQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4991.6 Da Synthesis and purification methods: S02, P02 LCMS:A02, Rt:12.75min, m / 3:1665.3, m / 4:1248.9, m / 5:999.2

[0098] compound 9 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17I,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEEIQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5029.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.60min, m / 3:1677.0, m / 4:-, m / 5:-

[0099] compound 10 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,10A,17T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADASPEETQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4917.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.21min, m / 3:-, m / 4:1230.0, m / 5:-

[0100] compound 11 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17I,18Q,19Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEEIQQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4959.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.79min, m / 3:-, m / 4:1241.0, m / 5:-

[0101] compound 12 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13P,14G,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAPGEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4957.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.87min, m / 3:-, m / 4:1240.0, m / 5:-

[0102] compound 13 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 13A, 18Q, 19Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAAPEELQQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4943.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.70min, m / 3:-, m / 4:1237.0, m / 5:-

[0103] compound 14 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,10A,13T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADATPEELQRYYVSLRHYYNWLTRQRY-NH2 [ka] Molecular weight (calculated): 4943.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.96min, m / 3:1648.0, m / 4:-, m / 5:-

[0104] compound 15 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17I,18Q,21E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEEIQRYEVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4953.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.22min, m / 3:1652.0, m / 4:-, m / 5:-

[0105] compound 16 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17T,18Q,22V,23T,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEETQRYYVTLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4989.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.28min, m / 3:-, m / 4:1248.0, m / 5:-

[0106] compound 17 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 15A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPAELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4929.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.77min, m / 3:1643.0, m / 4:-, m / 5:-

[0107] compound 18 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13E,18Q,19Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAEPEELQQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5001.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.27min, m / 3:-, m / 4:1251.0, m / 5:-

[0108] compound 19 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 10A, 18Q, 19Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADASPEELQQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4901.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.90min, m / 3:1634.0, m / 4:-, m / 5:-

[0109] compound 20 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 13A, 18Q, 22V, 23E, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAAPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5013.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.72min, m / 3:-, m / 4:1253.0, m / 5:-

[0110] compound 21 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,19K,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQKYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4959.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.62min, m / 3:-, m / 4:1241.0, m / 5:-

[0111] compound 22 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22T,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYTSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4989.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.63min, m / 3:1664.0, m / 4:-,

[0112] compound 23 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,6A,7K,9E,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEEIQRYYVSLRHYYNWLTRQRY-NH2

[0113] [ka] Molecular weight (calculated): 4929.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.82min, m / 3:-, m / 4:1233.0, m / 5:-

[0114] compound 24 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22V,26K,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSLRKYYNWLTRQRY-NH2 Molecular weight (calculated): 4978.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.70min, m / 3:1661.0, m / 4:-, m / 5:-

[0115] compound 25 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11E, 14A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASAEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4975.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.74min, m / 3:-, m / 4:1245.0, m / 5:-

[0116] compound 26 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9P,13T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PPEDATPEELQRYYVSLRHYYNWLTRQRY-NH2

[0117] [ka] Molecular weight (calculated): 4969.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.74min, m / 3:-, m / 4:1243.0, m / 5:-

[0118] compound 27 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9P,13E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PPEDAEPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4997.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.11min, m / 3:1667.0, m / 4:-, m / 5:-

[0119] compound 28 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12T,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDTSPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5059.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.77min, m / 3:1688.0, m / 4:-, m / 5:-

[0120] compound 29 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,10A,11P,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEAPASPEELQRYYVELRHYYNWLTRQRY-NH2

[0121] [ka] Molecular weight (calculated): 4953.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.97min, m / 3:-, m / 4:1239.0, m / 5:-

[0122] compound 30 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 10A, 14E, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADASEEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4961.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.47min, m / 3:-, m / 4:1241.0, m / 5:-

[0123] compound 31 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 17T, 18Q, 22V, 23A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEETQRYYVALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4959.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.26min, m / 3:1654.0, m / 4:-, m / 5:-

[0124] compound 32 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12T,18Q,21E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDTSPEELQRYEVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4983.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.46min, m / 3:-, m / 4:1247.0, m / 5:-

[0125] compound 33 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11P,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEPASPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5011.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.85min, m / 3:-, m / 4:1254.0, m / 5:-

[0126] compound 34 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22V,24T,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSTRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4975.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.20min, m / 3:1660.0, m / 4:-, m / 5:-

[0127] compound 35 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13A,17T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAAPEETQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4959.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.45min, m / 3:-, m / 4:1240.0, m / 5:-

[0128] compound 36 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 8A, 9E, 13E, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)AEEDAEPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5003.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.34min, m / 3:-, m / 4:1252.0, m / 5:-

[0129] compound 37 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17T,18Q,21E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEETQRYEVSLRHYYNWLTRQRY-NH2

[0130] [ka] Molecular weight (calculated): 4941.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:8.97min, m / 3:1649.0, m / 4:-, m / 5:-

[0131] compound 38 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9P,18Q,22V,23A,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PPEDASPEELQRYYVALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4939.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.75min, m / 3:-, m / 4:1236.0, m / 5:-

[0132] compound 39 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9P,10A,13E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PPADAEPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4939.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.18min, m / 3:-, m / 4:1236.0, m / 5:-

[0133] compound 40 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13T,17T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDATPEETQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4989.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:8.84min, m / 3:1664.0, m / 4:-, m / 5:-

[0134] compound 41 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,13T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEATPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5015.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.93min, m / 3:-, m / 4:1255.0, m / 5:-

[0135] compound 42 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11A, 18Q, 22V, 24T, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEAASPEELQRYYVSTRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4931.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.35min, m / 3:-, m / 4:1234.0, m / 5:-

[0136] compound 43 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,10A,11P,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEAPASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4911.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.86min, m / 3:1638.0, m / 4:-, m / 5:-

[0137] compound 44 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,18Q,22V,28Y,30W,31I]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELQRYYVSLRHYYNWITRQRY-NH2 Molecular weight (calculated): 5001.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.66min, m / 3:1668.0, m / 4:-, m / 5:-

[0138] compound 45 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,16S,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPESLQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4959.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.96min, m / 3:-, m / 4:1240.0, m / 5:-

[0139] compound 46 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5001.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.80min, m / 3:1668.0, m / 4:-, m / 5:-

[0140] compound 47 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9P,10A,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PPADASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4897.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.60min, m / 3:-, m / 4:1224.0, m / 5:-

[0141] compound 48 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12T,13E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDTEPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5059.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.08min, m / 3:1688.0, m / 4:-, m / 5:-

[0142] compound 49 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,19Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQQYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5001.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.95min, m / 3:-, m / 4:1251.0, m / 5:-

[0143] compound 50 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,14A,18Q,22V,28Y,30W,31I]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASAEELQRYYVSLRHYYNWITRQRY-NH2 Molecular weight (calculated): 4961.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.33min, m / 3:-, m / 4:1241.0, m / 5:-

[0144] compound 51 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 8A, 9E, 11E, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)AEEEASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4975.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.07min, m / 3:1659.0, m / 4:-, m / 5:-

[0145] compound 52 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 8A, 9E, 14E, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)AEEDASEEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4993.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.76min, m / 3:-, m / 4:1249.0, m / 5:-

[0146] compound 53 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,10A,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADASPEEIQRYYVSLRHYYNWLTRQRY-NH2

[0147] [ka] Molecular weight (calculated): 4929.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.72min, m / 3:-, m / 4:1233.0, m / 5:-

[0148] compound 54 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4987.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.77min, m / 3:-, m / 4:-, m / 5:997.0

[0149] compound 55 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17A,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEAQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4945.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.25min, m / 3:1649.0, m / 4:-, m / 5:-

[0150] compound 56 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 10A, 13E, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADAEPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.17min, m / 3:-, m / 4:1244.0, m / 5:-

[0151] compound 57 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,14A,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASAEEIQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4961.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.50min, m / 3:-, m / 4:1241.0, m / 5:-

[0152] compound 58 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,19Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4959.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.87min, m / 3:-, m / 4:1241.0, m / 5:-

[0153] compound 59 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17T,18E,19Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEETEQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4948.5 Da Synthesis and purification methods: S02, P02 LCMS:A02, Rt:13.67min, m / 3:1651.0, m / 4:1238.0, m / 5:990.5

[0154] compound 60 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11A, 18E, 19Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEAASPEELEQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4916.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.30min, m / 3:-, m / 4:1230.0, m / 5:-

[0155] compound 61 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9P,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PPEDASPEEIQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4955.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.51min, m / 3:-, m / 4:1240.0, m / 5:-

[0156] compound 62 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,18E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PGEDASPEELERYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4916.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.91min, m / 3:-, m / 4:-, m / 5:983.0

[0157] compound 63 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 18Q, 22V, 26A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSLRAYYNWLTRQRY-NH2 Molecular weight (calculated): 4921.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.10min, m / 3:1641.0, m / 4:-, m / 5:-

[0158] compound 64 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PGEDASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4915.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.65min, m / 3:1639.0, m / 4:-, m / 5:-

[0159] compound 65 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22V,23E,24I,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVEIRHYYNWLTRQRY-NH2

[0160] [ka] Molecular weight (calculated): 5029.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.82min, m / 3:-, m / 4:1258.0, m / 5:-

[0161] compound 66 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,14A,17T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASAEETQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4949.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.61min, m / 3:-, m / 4:1238.0, m / 5:-

[0162] compound 67 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12S,13A,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDSAPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4987.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.60min, m / 3:-, m / 4:1248.0, m / 5:-

[0163] compound 68 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,18Q,19A,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELQAYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4916.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.13min, m / 3:-, m / 4:1230.0, m / 5:-

[0164] compound 69 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12S,14A,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDSSAEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4977.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.26min, m / 3:-, m / 4:1245.0, m / 5:-

[0165] compound 70 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11A, 18Q, 21E, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEAASPEELQRYEVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4909.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.55min, m / 3:1638.0, m / 4:-, m / 5:-

[0166] compound 71 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,15S,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPSELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4959.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.96min, m / 3:-, m / 4:1242.0, m / 5:-

[0167] compound 72 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,12G,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEGSPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4987.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.87min, m / 3:-, m / 4:1248.0, m / 5:-

[0168] compound 73 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11E, 18Q, 22V, 26A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELQRYYVSLRAYYNWLTRQRY-NH2 Molecular weight (calculated): 4935.6 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:12.23min, m / 3:1646.8, m / 4:1235.0, m / 5:988.0

[0169] compound 74 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 14A, 18Q, 22V, 23A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASAEELQRYYVALRHYYNWLTRQRY-NH2

[0170] [ka] Molecular weight (calculated): 4945.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.72min, m / 3:1650.0, m / 4:-, m / 5:-

[0171] compound 75 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 14A, 18Q, 22V, 23T, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASAEELQRYYVTLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4975.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.74min, m / 3:-, m / 4:1244.0, m / 5:-

[0172] compound 76 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,18Q,22V,28Y,30A,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PGEDASPEELQRYYVSLRHYYNALTRQRY-NH2

[0173] [ka] Molecular weight (calculated): 4800.4 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.12min, m / 3:-, m / 4:1201.0, m / 5:-

[0174] compound 77 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,14E,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASEEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5061.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.44min, m / 3:-, m / 4:1266.0, m / 5:-

[0175] compound 78 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13E,18Q,19Q,22V,23T,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAEPEELQQYYVTLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5043.7 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:12.75min, m / 3:1682.6, m / 4:1262.1, m / 5:1009.7

[0176] compound 79 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,14E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASEEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5033.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.66min, m / 3:-, m / 4:1260.0, m / 5:-

[0177] compound 80 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,17T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEETQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4989.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.19min, m / 3:-, m / 4:1248.0, m / 5:-

[0178] compound 81 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22V,24I,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSIRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4987.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.72min, m / 3:1664.0, m / 4:-, m / 5:-

[0179] compound 82 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 16A, 18Q, 22V, 23A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEALQRYYVALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4913.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.28min, m / 3:-, m / 4:1229.0, m / 5:-

[0180] compound 83 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 10A, 15A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADASPAELQRYYVSLRHYYNWLTRQRY-NH2

[0181] [ka] Molecular weight (calculated): 4871.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.85min, m / 3:-, m / 4:1219.0, m / 5:-

[0182] compound 84 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEEIQRYYVSLRHYYNWLTRQRY-NH2 [ka] Molecular weight (calculated): 4987.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.60min, m / 3:1664.0, m / 4:-, m / 5:-

[0183] compound 85 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 18Q, 21A, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYAVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4895.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.82min, m / 3:1633.0, m / 4:-, m / 5:-

[0184] compound 86 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 10A, 18Q, 21E, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADASPEELQRYEVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4895.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.44min, m / 3:-, m / 4:1224.0, m / 5:-

[0185] compound 87 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12S,15A,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDSSPAELQRYYVSLRHYYNWLTRQRY-NH2

[0186] [ka] Molecular weight (calculated): 4945.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.82min, m / 3:-, m / 4:1237.0, m / 5:-

[0187] compound 88 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9P,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PPEDASPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4997.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.62min, m / 3:-, m / 4:1250.0, m / 5:-

[0188] compound 89 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,13E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEAEPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5043.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.08min, m / 3:-, m / 4:1261.0, m / 5:-

[0189] compound 90 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,21E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYEVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4953.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.46min, m / 3:1651.0, m / 4:-, m / 5:-

[0190] compound 91 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13P,14A,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAPAEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5013.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:11.44min, m / 3:-, m / 4:1254.0, m / 5:-

[0191] compound 92 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDTSPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5017.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.76min, m / 3:-, m / 4:1256.0, m / 5:-

[0192] compound 93 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 14A, 18Q, 19K, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASAEELQKYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4933.6 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:12.03min, m / 3:1646.0, m / 4:1234.3, m / 5:987.4

[0193] compound 94 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17T,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEETQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5017.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.15min, m / 3:-, m / 4:1256.0, m / 5:-

[0194] compound 95 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,15A,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPAEIQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4929.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.69min, m / 3:1644.0, m / 4:-, m / 5:-

[0195] compound 96 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 10A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4929.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.70min, m / 3:1644.0, m / 4:-, m / 5:-

[0196] compound 97 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 18Q, 22V, 23A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.86min, m / 3:-, m / 4:1244.0, m / 5:-

[0197] compound 98 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22S,23A,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYSALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4959.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.71min, m / 3:1654.0, m / 4:-, m / 5:- compound 99 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13E,14A,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAEAEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5003.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.61 min, m / 3:1668.0, m / 4:-, m / 5:-

[0198] compound 100 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,6A,7K,9P,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PPEDASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4897.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.76min, m / 3:-, m / 4:1225.0, m / 5:-

[0199] Compound 101 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13T,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDATPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5043.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.92min, m / 3:-, m / 4:1261.0, m / 5:-

[0200] Compound 102 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 18Q, 22V, 23T, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVTLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5001.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.88min, m / 3:1668.0, m / 4:-, m / 5:-

[0201] Compound 103 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,6A,7K,9E,14E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEDASEEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4961.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.03min, m / 3:1654.0, m / 4:-, m / 5:-

[0202] Compound 104 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 14A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASAEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4963.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.39min, m / 3:-, m / 4:1241.0, m / 5:-

[0203] compound 105 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13E,18Q,19E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAEPEELQEYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5002.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.41min, m / 3:-, m / 4:1251.0, m / 5:-

[0204] compound 106 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,6A,7K,9E,13T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEDATPEELQRYYVSLRHYYNWLTRQRY-NH2

[0205] [ka] Molecular weight (calculated): 4943.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.03min, m / 3:-, m / 4:1237.0, m / 5:-

[0206] Compound 107 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 18Q, 19K, 22V, 23A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQKYYVALRHYYNWLTRQRY-NH2

[0207] [ka] Molecular weight (calculated): 4943.6 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:11.80min, m / 3:1648.6, m / 4:1236.9, m / 5:989.5

[0208] compound 108 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5029.6 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:11.47min, m / 3:1678.1, m / 4:1258.1, m / 5:1006.7

[0209] Compound 109 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEAASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4943.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.90min, m / 3:1649.0, m / 4:-, m / 5:-

[0210] compound 110 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13E,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAEPEEIQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5029.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.10min, m / 3:-, m / 4:1258.0, m / 5:-

[0211] Compound 111 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13E,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAEPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5071.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.17min, m / 3:-, m / 4:1268.0, m / 5:-

[0212] compound 112 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDATPEELQRYYVSLRHYYNWLTRQRY-NH2 [ka] Molecular weight (calculated): 5001.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.85min, m / 3:-, m / 4:1252.0, m / 5:-

[0213] compound 113 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 8A, 9E, 13T, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)AEEDATPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4975.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.22min, m / 3:1659.0, m / 4:-, m / 5:-

[0214] compound 114 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22V,28H,29W,30Y,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSLRHYHWYLTRQRY-NH2 Molecular weight (calculated): 5010.6 Da Synthesis and purification methods: S02, P02 LCMS:A02, Rt:12.38min, m / 3:1671.2, m / 4:1253.9, m / 5:-

[0215] compound 115 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11E, 16A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEALQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4943.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.09min, m / 3:-, m / 4:1237.0, m / 5:-

[0216] compound 116 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 13A, 14A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAAAEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 0.0 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:11.36min, m / 3:-, m / 4:1238.0, m / 5:-

[0217] compound 117 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 6A, 7K, 9E, 18Q, 22V, 23A, 28Y, 30W, 31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVALRHYYNWLTRQRY-NH2

[0218] [ka] Molecular weight (calculated): 4913.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.08min, m / 3:-, m / 4:1228.0, m / 5:-

[0219] compound 118 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 14A, 15A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASAAELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4903.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.49min, m / 3:1636.0, m / 4:-, m / 5:-

[0220] Compound 119 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,18Q,22V,23T,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELQRYYVTLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5015.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.99min, m / 3:-, m / 4:1254.0, m / 5:-

[0221] compound 120 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,13E,14E,18Q,19E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PGEDAEEEELQEYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4962.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.78min, m / 3:-, m / 4:1241.0, m / 5:-

[0222] compound 121 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 6A, 7K, 9E, 10A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEADASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4871.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.95min, m / 3:1624.0, m / 4:m / 5:-

[0223] compound 122 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 13A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAAPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.55min, m / 3:1658.0, m / 4:-, m / 5:-

[0224] compound 123 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22V,28W,29Y,30H,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSLRHYWYHLTRQRY-NH2 Molecular weight (calculated): 5010.6 Da Synthesis and purification methods: S02, P02 LCMS:A02, Rt:9.68min, m / 3:1671.7, m / 4:1253.7, m / 5:-

[0225] compound 124 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13A,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAAPEEIQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.55min, m / 3:-, m / 4:1244.0, m / 5:-

[0226] compound 125 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 18Q, 22V, 28Y, 30W, 31A]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PGEDASPEELQRYYVSLRHYYNWATRQRY-NH2 Molecular weight (calculated): 4873.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.06min, m / 3:1625.0, m / 4:-, m / 5:-

[0227] compound 126 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,6A,7K,9E,12S,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEDSSPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4945.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.89min, m / 3:1649.0, m / 4:-, m / 5:-

[0228] compound 127 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 6A, 7K, 9E, 14A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEDASAEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4903.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.80min, m / 3:-, m / 4:1226.0, m / 5:-

[0229] compound 128 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13P,14A,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAPAEEIQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:11.28min, m / 3:1658.0, m / 4:-, m / 5:-

[0230] compound 129 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17T,18Q,22T,23A,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEETQRYYTALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4961.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.22min, m / 3:-, m / 4:1241.0, m / 5:-

[0231] compound 130 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12T,14A,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDTSAEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4991.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.30min, m / 3:1665.0, m / 4:-, m / 5:-

[0232] compound 131 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 8A, 9E, 18Q, 22V, 23E, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)AEEDASPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5002.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.10min, m / 3:-, m / 4:1251.0, m / 5:-

[0233] compound 132 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,19K,22V,23T,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQKYYVTLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4973.6 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:11.78min, m / 3:1659.4, m / 4:1244.6, m / 5:995.3

[0234] compound 133 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 17V, 18Q, 22V, 23E, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEEVQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5015.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.45min, m / 3:-, m / 4:1254.0, m / 5:-

[0235] compound 134 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17I,18Q,22T,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEEIQRYYTELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5031.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.54min, m / 3:-, m / 4:1258.0, m / 5:-

[0236] compound 135 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 10A, 18Q, 22V, 23E, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADASPEELQRYYVELRHYYNWLTRQRY-NH2

[0237] [ka] Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.81min, m / 3:-, m / 4:1244.0, m / 5:-

[0238] compound 136 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,10A,12S,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADSSPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4945.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.79min, m / 3:1649.0, m / 4:-, m / 5:-

[0239] compound 137 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22V,28Y,30W,31I]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSLRHYYNWITRQRY-NH2 Molecular weight (calculated): 4987.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.56 min, m / 3:1664.0, m / 4:-, m / 5:-

[0240] compound 138 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 6A, 7K, 9E, 18Q, 19Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4901.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.03min, m / 3:-, m / 4:1226.0, m / 5:-

[0241] compound 139 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,12S,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEESSPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5017.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.79min, m / 3:-, m / 4:1256.0, m / 5:-

[0242] compound 140 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,18E,19Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PGEDASPEELEQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4888.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.01min, m / 3:-, m / 4:1223.0, m / 5:-

[0243] compound 141 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11A, 18Q, 22V, 24A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEAASPEELQRYYVSARHYYNWLTRQRY-NH2 Molecular weight (calculated): 4901.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.46min, m / 3:-, m / 4:1227.0, m / 5:-

[0244] compound 142 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9P,11E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PPEEASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4969.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.79min, m / 3:-, m / 4:1243.0, m / 5:-

[0245] compound 143 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13T,18Q,22V,23A,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDATPEELQRYYVALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4985.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.10min, m / 3:1662.0, m / 4:-, m / 5:-

[0246] compound 144 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 8A, 9E, 18Q, 19Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)AEEDASPEELQQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4933.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.14min, m / 3:1645.0, m / 4:-, m / 5:-

[0247] compound 145 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12S,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDSSPEEIQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5003.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.74min, m / 3:-, m / 4:1251.0, m / 5:-

[0248] compound 146 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,18Q,22V,24T,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELQRYYVSTRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4989.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.22min, m / 3:-, m / 4:1248.0, m / 5:-

[0249] compound 147 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17T,18Q,19K,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEETQKYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4947.5 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:9.18min, m / 3:1650.3, m / 4:1238.1, m / 5:990.4

[0250] compound 148 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13P,14A,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAPAEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:11.20min, m / 3:-, m / 4:1242.0, m / 5:-

[0251] compound 149 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11A, 18Q, 22V, 23E, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEAASPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4985.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.99min, m / 3:-, m / 4:1248.0, m / 5:-

[0252] compound 150 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13E,18Q,19K,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAEPEELQKYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5001.6 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:11.23min, m / 3:1668.7, m / 4:1251.5, m / 5:1001.2

[0253] Compound 151 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 10A, 11E, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEAEASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4943.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.87min, m / 3:-, m / 4:1237.0, m / 5:-

[0254] compound 152 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,8A,9E,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)AEEDASPEEIQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4961.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.95min, m / 3:1654.0, m / 4:-, m / 5:-

[0255] compound 153 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 8V, 9E, 11E, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)VEEEASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5003.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.62min, m / 3:-, m / 4:-, m / 5:1001

[0256] compound 154 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,18Q,21E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELQRYEVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4967.6 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:10.32min, m / 3:1657.2, m / 4:1243.0, m / 5:994.4

[0257] compound 155 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEETQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4975.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.19min, m / 3:1659.0, m / 4:-, m / 5:-

[0258] compound 156 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,14E,18E,19Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASEEELEQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4992.5 Da Synthesis and purification methods: S02, P02 LCMS:A02, Rt:13.23min, m / 3:1665.6, m / 4:1248.9, m / 5:999.2

[0259] compound 157 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,6A,7K,9E,17T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEETQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4917.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.28min, m / 3:1640.0, m / 4:-, m / 5:-

[0260] compound 158 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22V,28W,30Y,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSLRHYWNYLTRQRY-NH2 Molecular weight (calculated): 4987.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.09min, m / 3:-, m / 4:1248.0, m / 5:-

[0261] compound 159 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 10A, 18E, 19Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADASPEELEQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4902.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.13min, m / 3:-, m / 4:1226.0, m / 5:-

[0262] compound 160 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,10A,13E,18Q,22T,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADAEPEELQRYYTSLRHYYNWLTRQRY-NH2

[0263] [ka] Molecular weight (calculated): 4973.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.10min, m / 3:-, m / 4:1244.0, m / 5:-

[0264] compound 161 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13T,18Q,19Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDATPEELQQYYVSLRHYYNWLTRQRY-NH2

[0265] [ka] Molecular weight (calculated): 4973.6 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:11.90min, m / 3:1658.2, m / 4:1244.5, m / 5:995.7

[0266] compound 162 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 18Q, 21E, 22V, 26A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYEVSLRAYYNWLTRQRY-NH2 Molecular weight (calculated): 4887.5 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:11.22min, m / 3:1630.5, m / 4:1223.0, m / 5:978.3

[0267] compound 163 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11A, 18Q, 22V, 23A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEAASPEELQRYYVALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4927.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.16min, m / 3:-, m / 4:1234.0, m / 5:-

[0268] compound 164 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,14E,18Q,19E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASEEELQEYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4992.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.65min, m / 3:1665.0, m / 4:-, m / 5:-

[0269] compound 165 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 18Q, 21Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYQVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4952.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.26min, m / 3:-, m / 4:1239.0, m / 5:-

[0270] compound 166 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9P,10A,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PPADASPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4939.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.58 min, m / 3:1647.0, m / 4:-, m / 5:-

[0271] compound 167 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,19Q,21E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQQYEVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4925.5 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:10.95min, m / 3:1643.1, m / 4:1232.5, m / 5:985.5

[0272] compound 168 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13E,18Q,22V,28Y,30W,31I]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAEPEELQRYYVSLRHYYNWITRQRY-NH2 Molecular weight (calculated): 5029.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.66min, m / 3:1678.0, m / 4:-, m / 5:-

[0273] compound 169 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11E, 18Q, 22V, 23A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELQRYYVALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4985.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.96min, m / 3:1663.0, m / 4:-, m / 5:-

[0274] compound 170 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,18E,19Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELEQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4974.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.18min, m / 3:-, m / 4:1244.0, m / 5:-

[0275] Compound 171 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13T,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDATPEEIQRYYVSLRHYYNWLTRQRY-NH2

[0276] [ka] Molecular weight (calculated): 5001.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.82min, m / 3:-, m / 4:1251.0, m / 5:-

[0277] compound 172 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13E,18Q,22V,23A,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAEPEELQRYYVALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5013.6 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:12.87min, m / 3:1672.6, m / 4:1254.6, m / 5:1003.6

[0278] compound 173 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 6A, 7K, 9E, 18Q, 22V, 23E, 28Y, 30W, 31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.91min, m / 3:-, m / 4:1245.0, m / 5:-

[0279] compound 174 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 6A, 7K, 9E, 13E, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEDAEPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.27min, m / 3:-, m / 4:1244.0, m / 5:-

[0280] compound 175 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 13A, 18Q, 22V, 23A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAAPEELQRYYVALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4955.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.87min, m / 3:1653.0, m / 4:-, m / 5:-

[0281] compound 176 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,14E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASEEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5019.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.40min, m / 3:1674.0, m / 4:-, m / 5:-

[0282] compound 177 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12S,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDSSPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5045.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.85min, m / 3:-, m / 4:1262.0, m / 5:-

[0283] compound 178 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13T,17T,18E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDATPEETERYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4990.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.35min, m / 3:-, m / 4:1249.0, m / 5:-

[0284] Compound 179 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 6A, 7K, 9E, 15A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEDASPAELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4871.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.96min, m / 3:1625.0, m / 4:m / 5:-

[0285] compound 180 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17T,18Q,19Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEETQQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4947.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.27min, m / 3:1650.0, m / 4:-, m / 5:-

[0286] compound 181 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 10A, 18Q, 22V, 23A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADASPEELQRYYVALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4913.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.93min, m / 3:-, m / 4:1229.0, m / 5:-

[0287] compound 182 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12G,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDGSPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5015.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:11.02min, m / 3:1672.0, m / 4:-, m / 5:-

[0288] compound 183 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9P,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PPEDASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4955.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.46min, m / 3:1652.0, m / 4:-, m / 5:-

[0289] compound 184 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11A, 18Q, 22V, 23T, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEAASPEELQRYYVTLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4957.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.13min, m / 3:-, m / 4:1241.0, m / 5:-

[0290] compound 185 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5043.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.83min, m / 3:1683.0, m / 4:-, m / 5:-

[0291] compound 186 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 14A, 18Q, 22V, 23E, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASAEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5003.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.55min, m / 3:-, m / 4:1252.0, m / 5:-

[0292] compound 187 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 18Q, 22V, 27Q, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSLRHQYNWLTRQRY-NH2 Molecular weight (calculated): 4952.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.22min, m / 3:1652.0, m / 4:-, m / 5:-

[0293] compound 188 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAEPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5031.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.87min, m / 3:-, m / 4:1257.0, m / 5:-

[0294] compound 189 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 14E, 15A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASEAELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4961.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.40min, m / 3:-, m / 4:1241.0, m / 5:-

[0295] compound 190 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,13P,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEAPPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5011.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.32min, m / 3:-, m / 4:1254.0, m / 5:-

[0296] Compound 191 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18Q,22I,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYISLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5001.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.81min, m / 3:1668.0, m / 4:-, m / 5:-

[0297] compound 192 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 13A, 15A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAAPAELQRYYVSLRHYYNWLTRQRY-NH2

[0298] [ka] Molecular weight (calculated): 4913.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.60min, m / 3:-, m / 4:1229.0, m / 5:-

[0299] compound 193 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,14E,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASEEEIQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5019.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.37min, m / 3:1674.0, m / 4:-, m / 5:-

[0300] compound 194 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,5Hyp,7K,9E,18Q,22V,28Y,30W,31T,32L]hPYY(4-36) iVal-AHypEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSLRHYYNWTLRQRY-NH2 Molecular weight (calculated): 5003.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:8.84min, m / 3:-, m / 4:1252.0, m / 5:-

[0301] Compound 195 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 16A, 18Q, 22V, 23E, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEALQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.11min, m / 3:1658.0, m / 4:-, m / 5:-

[0302] compound 196 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,6A,7K,9P,13E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PPEDAEPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4939.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.28min, m / 3:-, m / 4:1236.0, m / 5:-

[0303] Compound 197 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 6A, 7K, 9E, 10A, 18Q, 22V, 23E, 28Y, 30W, 31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEADASPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4913.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.00min, m / 3:1639.0, m / 4:m / 5:-

[0304] Compound 198 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 13E, 16A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAEPEALQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.31min, m / 3:-, m / 4:1244.0, m / 5:-

[0305] Compound 199 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13E,17T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAEPEETQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5017.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.37min, m / 3:-, m / 4:1255.0, m / 5:-

[0306] compound 200 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,8Hyp,9E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)HypEEDASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5003.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.53min, m / 3:-, m / 4:1250.0, m / 5:-

[0307] Compound 201 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9Q,13E,18Q,19E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PQEDAEPEELQEYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5001.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.24min, m / 3:-, m / 4:1251.0, m / 5:-

[0308] Compound 202 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 13A, 18Q, 19K, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAAPEELQKYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4943.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.48min, m / 3:-, m / 4:1237.0, m / 5:-

[0309] compound 203 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,6A,7K,9E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSLRHYYNWLTRQRY-NH2

[0310] [ka] Molecular weight (calculated): 4929.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.83min, m / 3:1644.0, m / 4:-, m / 5:-

[0311] compound 204 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11E, 17V, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEEVQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4987.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.62min, m / 3:1663.0, m / 4:-, m / 5:-

[0312] compound 205 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,18Q,19K,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELQKYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4973.6 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:11.05min, m / 3:1659.2, m / 4:1244.4, m / 5:995.5

[0313] compound 206 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,18E,19Q,21E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELEQYEVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4926.5 Da Synthesis and purification methods: S02, P02 LCMS:A02, Rt:11.60min, m / 3:1643.3, m / 4:1232.8, m / 5:986.2

[0314] compound 207 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 6A, 7K, 9E, 10A, 13E, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEADAEPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4913.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.37min, m / 3:-, m / 4:1229.0, m / 5:-

[0315] compound 208 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,14E,17T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASEEETQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5007.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.63min, m / 3:1670.0, m / 4:-, m / 5:-

[0316] compound 209 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12S,13E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDSEPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5045.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.09min, m / 3:-, m / 4:1263.0, m / 5:-

[0317] compound 210 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,8I,9E,11E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)IEEEASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5017.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:11.05min, m / 3:-, m / 4:1255.0, m / 5:-

[0318] compound 211 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13T,14A,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDATAEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4975.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.92min, m / 3:-, m / 4:1245.0, m / 5:-

[0319] compound 212 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12T,13A,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDTAPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5001.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.56min, m / 3:-, m / 4:1251.0, m / 5:-

[0320] compound 213 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,12T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEETSPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5031.7 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.79min, m / 3:1678.0, m / 4:-, m / 5:-

[0321] compound 214 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 14E, 18Q, 22V, 23A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASEEELQRYYVALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5003.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.70min, m / 3:1668.0, m / 4:-, m / 5:-

[0322] compound 215 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 15A, 18Q, 22V, 23E, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPAELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.86min, m / 3:-, m / 4:1244.0, m / 5:-

[0323] compound 216 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 6A, 7K, 9E, 18E, 19Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELEQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4902.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.24min, m / 3:1635.0, m / 4:-, m / 5:-

[0324] compound 217 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 15A, 18Q, 22V, 23A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPAELQRYYVALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4913.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.99min, m / 3:1639.0, m / 4:m / 5:-

[0325] compound 218 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,12S,18Q,22V,23A,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDSSPEELQRYYVALRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4987.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.00min, m / 3:-, m / 4:1247.0, m / 5:-

[0326] compound 219 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11E, 13A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEAAPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4985.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.41min, m / 3:-, m / 4:1247.0, m / 5:-

[0327] compound 220 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11A, 14A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEAASAEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4917.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.70min, m / 3:-, m / 4:1230.0, m / 5:-

[0328] compound 221 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13P,14E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAPEEELQRYYVSLRHYYNWLTRQRY-NH2

[0329] [ka] Molecular weight (calculated): 5029.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:11.00min, m / 3:-, m / 4:1258.0, m / 5:-

[0330] compound 222 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 14A, 18Q, 19Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASAEELQQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4933.5 Da Synthesis and purification methods: S02, P02 LCMS:A02, Rt:13.32min, m / 3:1645.5, m / 4:1234.4, m / 5:987.4

[0331] compound 223 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11A, 13E, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEAAEPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4985.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.21min, m / 3:-, m / 4:1247.0, m / 5:-

[0332] compound 224 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,11E,18E,19Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PGEEASPEELEQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4902.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.12min, m / 3:1634.0, m / 4:-, m / 5:-

[0333] compound 225 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,13E,18E,19Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PGEDAEPEELEQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4930.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.96min, m / 3:1644.0, m / 4:-, m / 5:-

[0334] compound 226 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11A,17T,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEAASPEETQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4931.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.26min, m / 3:1645.0, m / 4:-, m / 5:-

[0335] compound 227 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 8A, 9E, 18E, 19Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)AEEDASPEELEQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4934.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.38min, m / 3:-, m / 4:1235.0, m / 5:-

[0336] compound 228 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 18Q, 19Q, 22V, 26A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQQYYVSLRAYYNWLTRQRY-NH2 Molecular weight (calculated): 4893.5 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:12.98min, m / 3:1632.6, m / 4:1224.3, m / 5:979.6

[0337] compound 229 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 18Q, 22V, 24A, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSARHYYNWLTRQRY-NH2 Molecular weight (calculated): 4945.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.27min, m / 3:1650.0, m / 4:-, m / 5:-

[0338] compound 230 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,17I,18Q,22V,23A,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEEIQRYYVALRHYYNWLTRQRY-NH2

[0339] [ka] Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.81min, m / 3:-, m / 4:1243.0, m / 5:-

[0340] Compound 231 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,13T,18Q,19K,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDATPEELQKYYVSLRHYYNWLTRQRY-NH2

[0341] [ka] Molecular weight (calculated): 4973.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.79min, m / 3:-, m / 4:1245.0, m / 5:-

[0342] compound 232 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,6A,7K,9P,18Q,22V,23E,28Y,30W,31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PPEDASPEELQRYYVELRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4939.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.71min, m / 3:-, m / 4:1235.0, m / 5:-

[0343] compound 233 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 11A, 18Q, 19Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEAASPEELQQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4915.5 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:12.58min, m / 3:1639.6, m / 4:1230.1, m / 5:984.0

[0344] compound 234 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 6A, 7K, 9E, 11E, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APAK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELQRYYVSLRHYYNWLTRQRY-NH2

[0345] [ka] Molecular weight (calculated): 4943.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.96min, m / 3:1649.0, m / 4:-, m / 5:-

[0346] compound 235 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,14Hyp,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASHypEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5003.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.28min, m / 3:-, m / 4:1252.0, m / 5:-

[0347] compound 236 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,13P,14A,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEAPAEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4985.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:11.15min, m / 3:-, m / 4:1247.0, m / 5:-

[0348] compound 237 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 18Q, 22V, 23E, 24V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVEVRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5015.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.60min, m / 3:1672.0, m / 4:-, m / 5:-

[0349] compound 238 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,8T,9E,11E,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)TEEEASPEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5005.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.89min, m / 3:1669.0, m / 4:-, m / 5:-

[0350] compound 239 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,14E,18Q,21E,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASEEELQRYEVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4985.5 Da Synthesis and purification methods: S02, P02 LCMS:A02, Rt:11.55min, m / 3:1662.9, m / 4:1247.5, m / 5:998.0

[0351] compound 240 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 16A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEALQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4929.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.96min, m / 3:1643.0, m / 4:-, m / 5:-

[0352] compound 241 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,17I,18Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEEIQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 5001.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:9.70min, m / 3:-, m / 4:1251.0, m / 5:-

[0353] compound 242 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 10A, 14A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEADASAEELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4903.5 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.72min, m / 3:-, m / 4:1226.0, m / 5:-

[0354] compound 243 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A,7K,9E,11E,18Q,19Q,22V,28Y,30W,31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEEASPEELQQYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4973.6 Da Synthesis and purification methods: S03, P02 LCMS:A02, Rt:11.78min, m / 3:1659.0, m / 4:1244.6, m / 5:995.5

[0355] compound 244 N{alpha-4}-(3-methylbutanoyl)-N{epsilon-7}-[2-(2-{2-[2-(2-{2-[(4S)-4-carboxy-4-(17-carboxyheptadecanamido)butanamido]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetamido]-[4A, 7K, 9E, 13E, 15A, 18Q, 22V, 28Y, 30W, 31L]hPYY(4-36) iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDAEPAELQRYYVSLRHYYNWLTRQRY-NH2 Molecular weight (calculated): 4971.6 Da Synthesis and purification methods: S01, P01 LCMS:A01, Rt:10.08min, m / 3:1658.0, m / 4:-, m / 5:-

[0356] The following compound, disclosed as compound 38 in International Publication No. WO 2016 / 198682, was synthesized as a reference compound. Reference compound 1 iVal-RPEK(C18DA-gGlu-OEG1-OEG2-)PGEDASPEELQRYYVSLRHYYNWLTRQRY-NH2 (SEQ ID NO: 249)

[0357] Further compounds were synthesised as reference compounds. Reference compound 2 iVal-RPEK(C18DA-gGlu-OEG1-OEG2-)PGEDASPEELQRYYVSL A HYYNWLTRQRY-NH2 (SEQ ID NO: 250) Reference compound 3 iVal-RPEK(C18DA-gGlu-OEG1-OEG2-)PGEDASPEELQRYYVSLR A YYNWLTRQRY-NH2 (SEQ ID NO: 251) Reference compound 4 iVal-RPEK(C18DA-gGlu-OEG1-OEG2-)PGEDASPEELQRYYVSLRHYYNWLT A QRY-NH2 (SEQ ID NO: 252) Reference compound 5 iVal-RPEK(C18DA-gGlu-OEG1-OEG2-)PGEDASPEELQRYYVSLRHYYNWLTRQ A Y-NH2 (SEQ ID NO: 253)

[0358] The structure of Reference Compound 1 is identical to that of Compound 64, except for the alanine at position 4. This R4A mutation results in a compound that is much more soluble at pH 6.2 (0.5 mg / ml for Reference Compound 1 vs. 8.7 mg / ml for Compound 64). At the same time, high binding affinity and receptor activity are maintained in Compound 64 (see Table 2). Other arginine-to-alanine mutations at different positions (R25A in Reference Compound 2, R33A in Reference Compound 4, R35A in Reference Compound 5) or histidine-to-alanine mutation at position 26 (H26A in Reference Compound 3) negatively affect the binding affinity and receptor activity or physical stability of the resulting compound.

[0359] [Table 2] [Example]

[0360] The following examples illustrate certain specific embodiments of the present invention. The following examples were carried out using standard techniques that are well known and routine to those skilled in the art, unless otherwise specified.

[0361] Example 1 Radioligand binding competition assay (RLB) The filtered RLB assay was performed in a 96-well plate with a final volume of 100 μl per well. Lyophilized test peptides were dissolved in 100% dimethyl sulfoxide (DMSO) to a 1 mM stock solution and serially diluted in assay buffer (50 mM HEPES, 5 mM MgCl, 1 mM CaCl, pH 7.4) containing 0.2% ovalbumin. 10 μl / well of test peptide solution was added to the plate to give final concentrations ranging from 1 μM to 3 pM. Subsequently, human leukocyte ... 125 Ten μl of I-PYY(1-36) (Perkin Elmer) was added to each well to give a final concentration of 0.02 nM. Then, 80 μL of membrane (HTS066M, ChemiSCREEN™ Human Neuropeptide Y2 Receptor Membrane Preparation, CHEMICON) was added to each well to give a final protein concentration of 0.5 μg / well. The plate was sealed and incubated for 2 hours at room temperature on a plate shaker set at 400 rpm. The incubation was terminated by vacuum filtration onto GF / C filters presoaked in 0.5% polyethyleneimine (PEI) using a 96-well FilterMate™ harvester (Perkin Elmer), followed by four washes with 300 μl / well of ice-cold wash buffer (50 mM HEPES, 500 mM NaCl, pH 7.4). The filter plate was then dried at room temperature for 60 minutes, and the bottom of the plate was sealed with UniFilter-96 backing tape. Finally, 50 μl / well of scintillation counter cocktail (Microscint20, Packard) was added and radioactivity was counted in a Packard TopCount NXT scintillation counter. 50 The values ​​(half-maximal inhibitory concentrations of agonists) were calculated by nonlinear regression analysis of sigmoidal dose-response curves. The Ki values ​​of binding affinity were obtained by the Cheng-Prusoff equation (Ki = IC). 50 / (1+[L] / Kd)), where Kd is the receptor-specific dissociation constant measured previously (=0.07 nM for NPY2R) and [L] is 125 I-PYY(1-36) radioligand concentration.

[0362] The RLB results are summarized in Table 3 below. [Table 3-1]

[0363] [Table 3-2]

[0364] [Table 3-3]

[0365] [Table 3-4]

[0366] [Table 3-5]

[0367] [Table 3-6] In general, data obtained with the RLB assay are predictive of acute food intake inhibition in mice (Experiment 6).

[0368] Example 2 HTRF cAMP Gi assay Homogeneous time-resolved fluorescence (HTRF) technology optimized for Gi-coupled receptors is described in detail in the Cisbio cAMP Gi kit manual. Briefly, intracellular cAMP production results in competition between unlabeled cAMP and exogenously added d2-cAMP for an anti-cAMP antibody conjugated to a cryptate. CHO-K1 cells stably expressing human NPY1, NPY2, NPY4, and NPY5 receptors were used, with cells restored from frozen stock immediately prior to assay execution. 2,000 cells per well were applied to all four NPY receptor subtype assays. A 384-well format was used, with 5 μl of cells, 2.5 μl of peptide agonist, 2.5 μl of forskolin, and 5 μl of each fluorophore applied in a total volume of 20 μl. Cells were incubated with agonist peptides (11-point concentration-response curves) and forskolin (approximately 90% activity level, 3-11 μM forskolin) for 40 min at 37°C using DPBS containing 0.5 mM IBMX as the stimulation buffer. HTRF® detection reagent was added, and after incubation at room temperature for 1 h with shaking (2400 rpm), signals at 620 and 665 nm (raw counts: 665 / 620 ratio) were detected. Compound concentration-response evaluation was performed using 11 concentrations of agonist peptides (covering 3 decades). EC 50 Values ​​were calculated by nonlinear regression using a sigmoidal concentration response with variable slope.

[0369] In vitro activity results (EC 50 The values ​​(expressed as % values) are summarized in Table 4 below. [Table 4]

[0370] Example 3 Determining stability Peptides (as TFA salts) were weighed into filter units (Mini-UniPrep Syringeless Filter 0.45 μm, Whatman), and 0.1 M dibasic sodium phosphate buffer, pH 6.4 or 7.0, was added to achieve a final concentration of 10 mg / ml. The peptides were dissolved by shaking the filter units horizontally at 600 rpm for 2 hours at room temperature. Samples were filtered to remove any insoluble particles and diluted to 1 mg / ml in 50% acetonitrile. Controls were prepared by weighing the corresponding peptide and dissolving it in 50% acetonitrile to a final concentration of 1 mg / ml. Both the control and sample were analyzed by reverse-phase chromatography. The area under the peak of the sample was compared to the control, and solubility was calculated based on the ratio.

[0371] For each sample, the pH was measured and recorded. Typically, the pH of the buffer was reduced by 0.2-0.3 pH units due to the TFA content of the peptide. UPLC method: System: UltiMate 3000 UPLC, ThermoFisher Mobile phase A: 5% acetonitrile, 95% water, 0.03% trifluoroacetic acid Mobile phase B: 95% acetonitrile, 5% water, 0.03% trifluoroacetic acid Flow rate: 1ml / min Gradient: 0 to 100% mobile phase B (2 min) Column: Kinetix, 5 μm C8, 100 Å, 50 × 2.1 mm Column temperature: 50℃

[0372] The results of the solubility determination are summarized in Table 5 below. [Table 5-1]

[0373] [Table 5-2]

[0374] [Table 5-3]

[0375] [Table 5-4]

[0376] [Table 5-5]

[0377] Example 4 DLS research Aggregation, along with particle growth, in peptide solutions was detected by dynamic light scattering (DLS). Test peptides (5 mg / ml) were dissolved in 50 mM phosphate buffer with EDTA (0.05 mg / ml), which was adjusted to a final pH of 7.2. The solutions were filtered through a 0.2 μm filter and shaken on a laboratory shaker at approximately 150 rpm at room temperature for 5–7 days. Samples were analyzed with a particle size analyzer (DLS, Horiba Nano Particle Analyzer SZ-100) on day 0 and at the end of the study. Aggregate formation was detected by an increase in particle size over time and was evaluated as OK, indicating no increase in particle size, and NOK, indicating an increase in particle size.

[0378] The results from the DLS studies are summarized in Table 6. [Table 6]

[0379] Example 5 Mouse PK Pharmacokinetic parameters of the test compounds were determined after intravenous administration to NMRI mice. Male NMRI mice weighing approximately 30-40 g were obtained from either Charles River (Germany) or Janvier (France). Mice were housed in standard cages with a light-dark cycle of 12 hours dark and 12 hours light. Standardized diet and water were provided ad libitum throughout the experimental period. Each peptide was dissolved in 50 mM phosphate buffer (pH 7.0) containing 5% mannitol, and an intravenous dose of 30 nmol / kg was given via the tail vein.

[0380] Serial blood samples were collected from the saphenous vein at different time points up to 48 hours post-dose into tubes containing EDTA as an anticoagulant. After approximately 5 minutes of centrifugation, plasma samples were transferred to a 96-well PCR plate, immediately frozen, and stored at approximately -20°C until analyzed for plasma concentrations by liquid chromatography-mass spectrometry (LC-MS / MS). Individual plasma concentration-time profiles were analyzed by a non-compartmental approach to determine the resulting pharmacokinetic parameters.

[0381] The measured mouse MRT of the PYY analogues according to the invention is comparable to that of reference compound 1 and exhibits a significantly longer half-life compared to that of hPYY(3-36).

[0382] Example 6 Effects on acute food intake in normal NMRI mice Five-week-old male NMRI mice were obtained from Charles River (Charles River, Research Models & Services Germany GmbH) or JanVier (JanVier Labs, France). Animals were housed in groups of four mice per cage under a 12 / 12-hour light / dark cycle with lights off at 3 PM. Room temperature was controlled at 21°C ± 1°C with 60% ± 20% humidity. Animals were fed a normal rodent diet (KLIBA Nafag 3430 or Altromin 1324, Brogaarden, Denmark) and tap water ad libitum.

[0383] Animals were transferred to a real-time food intake monitoring system, the HM-2 system (MBRose, Denmark), 5–7 days before the start of the study and allowed to acclimate to the experimental conditions. Animals were uniquely identified by microchips, and each individual animal was identified by its microchip upon entering and exiting the food channel. Randomization of mice (n = 7–8) into each study group was based on body weight measured the day before the start of the study. A vehicle-treated (50 mM phosphate buffer, pH 7, containing 5% mannitol) group was included in each experiment. Animals were fasted 6 h before the start of the night phase. One hour before the dark phase, animals received a single subcutaneous dose of the test peptide (10 nmol / kg). Food intake was reported hourly for a 24-h period. Food intake of the treatment groups was normalized (in %) to the mean food intake of the vehicle-receiving group (Table 7). Statistical significance was assessed using one-way analysis of variance with Tukey's multiple comparison test. P<0.05 was considered statistically significant.

[0384] [Table 7-1]

[0385] [Table 7-2]

[0386] Example 7 Activity after incubation in solutions of different pH values The peptide (as the TFA salt) was weighed into a filter unit (Mini-UniPrep Syringeless Filter 0.45 μm, Whatman), and 0.1 M dibasic sodium phosphate buffer at pH 6.4 or 7.4, or 0.2 M TRIS buffer at pH 8.3, respectively, was added to achieve a final concentration of 10 mg / ml. The peptide was (partially) dissolved by shaking the filter unit horizontally at approximately 400 rpm for 2 hours at room temperature. The sample was filtered to remove any insoluble particles. The filtrate was then subjected to the binding assay described in Example 1. The apparent binding affinities (Ki) reported in Table 8 are calculated based on an assumed concentration of 10 mg / ml. The compounds of the present invention are active in binding assays after incubation in solutions at different pH values, including pH 6. This demonstrates the fundamental feasibility of liquid formulations of compounds according to the present invention at about pH 6 (pH range of about 6 to about 8).

[0387] In contrast, after incubation at about pH 6, solutions of reference compound 1 (after filtration) show a weak response in the binding assay (apparent significant (more than 35-fold) loss of affinity due to the low solubility of reference compound 1 in buffered media at pH 6). Thus, the inherently low solubility of reference compound 1 at about pH 6 limits the formulation scope of liquid formulations of reference compound 1 in the physiological pH range of 6-8.

[0388] [Table 8]

Claims

1. 1. A PYY analog comprising an amino acid sequence corresponding to the amino acid sequence of hPYY(3-36), having the formula: R 1 -Z-R 2 wherein R 1 is hydrogen, -C(O)C 1-6 Alkyl, —C(O)C 6 H 6 , -C(O)C 3-6 cycloalkyl, or C 1-6 is alkyl, R 2 is OH or NHR 3 wherein R 3 is hydrogen or C 1-3 is alkyl, Z is an amino acid sequence selected from SEQ ID NOs: 6-8, 10-15, 17-31, 33-35, 37-46, 48-51, 53-58, 60-79, 81-86, 88-95, 97-117, 119-124, 126-133, 135-156, 158-182, 184-190, 192-197, 199, 200, 202-210, 212, 213, 215, 218-241, 243-248; a half-life extending group is attached to the epsilon amino group of the lysine at position 7; The PYY analogue, wherein the half-life extending group consists of a lipophilic substituent X and a linker U, wherein the linker U is attached to the epsilon-amino group of a lysine, and wherein X is attached to U, wherein X is selected from the group consisting of 15-carboxy-pentadecanoyl, 17-carboxy-heptadecanoyl (C18DA), and 19-carboxy-nonadecanoyl, and wherein U consists of one, two, or three submoieties independently selected from the group consisting of γ-Glu and OEG.

2. The half-life extending group is C18DA-γ-Glu-OEG-OEG-, i.e., 2. The PYY analog of claim 1, wherein:

3. PYY analogs are Compound 2 iVal-AHypeXK (C18DA-gGlu-OEG1-OEG2-)PeedaxaSpeedaxaQRyyyVsLrHyyyNwltrQRyy-Nh 2 、 Compound 3 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEG-ASP-QRYYYV-SLRHYYNW-WLRH-QRYY-NH 2 Compound 4 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDAQRYYYVSLRYHYYNYNWLQRYQRY-NH 2 、 Compound 6 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASP-QRY-YV-S-A-R-H-Y-N-W-L-T-R-QRY-N-H 2 、 Compound 7 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQAYYYYVSLRHYYYYNWLTRQRY-NH 2 、 Compound 8 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SEQ-YYYV-S-L-R-H-YYYN-W-L-T-R-Q-R-H-N-H 2 、 Compound 9 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQRYYYVHYYYNWWLTRQRYY-NH 2 、 Compound 10 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEADASPEEETQRYYYVSLRHYYNYNWLTRQRYYY-NH 2 、 Compound 11 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDAQQYYYYVSLRHYYYYNNWLQRYQRY-NH 2 、 Compound 13 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-APE-OEG1-OEG2-)PEEDA-APEEDA-QQYYYYVS-L-R-HYYYNYW-L-T-R-Q-R-H-Y-N-W 2 、 Compound 14 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEADAPTEEQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 15 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQRYYEHVSLRYHYYNYNWLTRQRYY-NH 2 、 Compound 16 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYVTLRHYYNWWLTRQRYY-NH 2 、 Compound 17 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPAESPALQRYYYVSLHRHYYNYNWLTRQRYY-NH 2 、 Compound 18 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-OEG 2 、 Compound 19 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEADASPEELQQYYYYVSLRHYYYYNWLTRQRY-NH 2 、 Compound 20 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-APE-QRYYYVHYYNYNWLTRQRYY-NH 2 、 Compound 21 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQKHYYYYVSLLRHYYYYNNWLLRQRY-NH 2 、 Compound 22 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYTSDSLRYHYYNYNWLQRYQRY-NH 2 、 Compound 23 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDAQRYYYYYVSLRHYYYYNYWWLTRQRYYY-NH 2 、 Compound 24 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYVSLRYKYYYNYWWLTRQRYY-NH 2 、 Compound 25 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEG-ASA-EEG-QRYYYVS-L-R-H-Y-N-W-L-T-R-QRYY-N-H 2 、 Compound 26 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PPEDA-QRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 27 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PPEDA-QRYYYVSLRHYYNYNWLTRQRYY-NH 2 、 Compound 29 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEA-ASP-QRYYYVH-YYYNYNW-LTR-QRYY-NH 2 、 Compound 30 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEADASEQRRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 31 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYYYVXYYYYYYWWWLTRQRYYY-NH 2 、 Compound 33 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-PEE-QRY-Y-Y-V-E-R-H-Y-Y-N-W-L-T-R-QRY-Y-N-H 2 、 Compound 34 iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYYVSTRHYYNWLTRQRY-NH 2 、 Compound 35 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-APE-ETQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 36 iVal-APE (C18DA-gGlu-OEG1-OEG2-) AEEGDAEEGPEEGQRRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 37 iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEETQRYEVSLRHYYNWLTRQRY-NH 2 、 Compound 38 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PPEDASPEDQRYYYVXYLHYYNWWLTRQRYY-NH 2 、 Compound 39 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PPDA-QRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 40 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDATPEEDQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 41 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-A-T-P-E-Q-R-Y-Y-V-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-N-H 2 、 Compound 42 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEAASPEEAQRYYYYYVSTRYHYYYYNWLRTRYQRY-NH 2 、 Compound 44 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASP-QRYYYVS-L-R-H-Y-Y-N-W-I-T-R-QRY-N-H 2 、 Compound 45 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEGASPEGSQRYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 46 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASPE-QRYYYVS-LHRHYYNYNW-LTRQRYY-NH 2 、 Compound 47 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PPADASPEEQRYYYVSLRYHYYNYNWLTRQRYY-NH 2 、 Compound 49 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDAQQYYYYVHYYYYNWWLTRQRY-NH 2 、 Compound 50 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SAEQRYYYVSLRYHYYNWWITRQRYY-NH 2 、 Compound 51 iVal-APE (C18DA-gGlu-OEG1-OEG2-) AEEG-AES-P-R-E 2 、 Compound 52 iVal-APE (C18DA-gGlu-OEG1-OEG2-) AEEGDASEEGDQRYYYVSLHRHYYNYNWLHTQRYY-NH 2 、 Compound 53 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEADASPEEGIQRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 54 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 56 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEADAQRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 57 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SAA-EEGIQRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 58 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQQYYYYVSLLRHYYYYNWLTRQRY-NH 2 、 Compound 59 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQYYYYVSLRHYYYYNWLTRQRY-NH 2 、 Compound 60 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEAASPEEAQYYYYVSLRHYYYYNWLTRQRY-NH 2 、 Compound 61 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PPEDASPEDQRYYYVSLRYHYYNYNWLTRQRYY-NH 2 、 Compound 62 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PGEDAS-SPEE-EEL-RHY-YYNW-L-T-R-Q-R-R-N-H 2 、 Compound 63 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYVSLRYYYNWWLTRQRYY-NH 2 、 Compound 64 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PGEDASPEELQRYYYVSLRYHYYNYNWLTRQRYY-NH 2 、 Compound 65 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQRYYYVHYYYNWWLTRQRYY-NH 2 、 Compound 66 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SAE-EATQRYYYVSL-RHYYYNWWLTRQRYY-NH 2 、 Compound 67 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDS APE QRYYYV SLRHYYNWWLTRQRYY-NH 2 、 Compound 68 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASPE-QAYYYYVS-LHRHYYYYNWWLTRQRY-NH 2 、 Compound 69 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDSSSAQRYYYYYVSLRYHYYYYNYWWLTRQRYYY-NH 2 、 Compound 70 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEAASPEEAQRYYEHVSLRHYYNYNWLTRQRYY-NH 2 、 Compound 71 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEG-ASPSELQRYYYVSLHRHYYNYNWLTRQRYY-NH 2 、 Compound 72 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEGSPEEGSQRYYYVSLRHYYNYNWLTRQRYY-NH 2 、 Compound 73 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASPE-QRYYYVSL-RXRYY-NWWL-TRXRYY-NW 2 、 Compound 74 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SASQR-R-Y-Y-V-A-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-N-H 2 、 Compound 75 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SASQR-R-Y-Y-V-T-L-R-H-Y-Y-N-W-L-T-R-QR-Y-N-H 2 、 Compound 77 iVal-AEK(318DA-gllu-E･11m-･.EEASEEEQQQQQQ((66666\6_\\\\ES] 2 、 Compound 78 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-OEG 2 、 Compound 79 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-A-S-E 2 、 Compound 80 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASP-QRY-YVS-L-R-H-Y-N-W-L-T-R-QRY-N-H 2 、 Compound 81 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDAQRYYYVSYRYYYNWWLTRQRYY-NH 2 、 Compound 82 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEALQRYYYVHYYNWWLTRQRYY-NH 2 、 Compound 84 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 85 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYAVSLRHYYNYNWLTRQRYY-NH 2 、 Compound 86 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEADASPEELQRYYEHVSLRYHYYNYWWLTRQRYY-NH 2 、 Compound 87 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDSSPYAELQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 88 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PPEDASPEDQRYYYVHYYNYNYWWLTRQRYY-NH 2 、 Compound 89 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEQRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 90 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYEHVSLRYHYYNYWWLTRQRYY-NH 2 、 Compound 91 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDAPAPAQRYYYYYVHYYYYNYWWLTRQRYYY-NH 2 、 Compound 93 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SAE-EEG-QKH-YYYYYVS-LHRHYYYYNNWL-LTRQRY-NH 2 、 Compound 94 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYVHYYNYNYWWLTRQRYY-NH 2 、 Compound 95 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPAESPIAEGIQRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 96 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEADASPEELQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 97 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQRYYYVHYYNYNWLTRQRYY-NH 2 、 Compound 98 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQRYYYSASALHYYNWWLTRQRYY-NH 2 、 Compound 99 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-EA-QRYYYVS-L-R-H-Y-N-W-L-T-R-QRYY-N-H 2 、 Compound 100 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PPEDASPEDQRYYYVSLRYHYYNYNWLTRQRYY-NH 2 、 Compound 101 iVal-AEK(318DA-gllu-E･11m-･.EEATPEEQQQQQQ +6 666!6!6!!?--8. 2 、 Compound 102 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQRYYYVTLRHYYYNWWLTRQRYY-NH 2 、 Compound 103 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PEEDASEEEGS 2 、 Compound 104 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SA-QRYYYVS-L-R-H-Y-N-W-L-T-R-QRYY-N-H 2 、 Compound 105 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-E 2 、 Compound 106 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PEEDATPEEDQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 107 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQKHYYYYVXHYYYYNNWLTRQRY-NH 2 、 Compound 108 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQRYYYVHYYNYNYWWLTRQRYY-NH 2 、 Compound 109 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEAASPEEAQRYYYVSLRHYYNYNWLTRQRYY-NH 2 、 Compound 110 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-EPEEDA-QRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 111 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-QRYYYVHYYNYNWWLTRQRYY-NH 2 、 Compound 112 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDATPPEEDAQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 113 iVal-APE (C18DA-gGlu-OEG1-OEG2-) AEEGDATQRYYYVSLRYHYYNYNWLTRQRYY-NH 2 、 Compound 115 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEASPEAALQRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 116 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDAAAAAEAEAQRYYYYYVSLRHYYYYNYWWLTRQRYYY-NH 2 、 Compound 117 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEDASQRYYYVXALHYYNWWLTRQRYY-NH 2 、 Compound 118 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SAA-A-EELQRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 119 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASP-QRYYYV-TLRHYYNYNW-LTRQRYY-NH 2 、 Compound 120 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PGEDA-EEG 2 、 Compound 122 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-APE-QRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 123 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYVSLRYHYWYHLYHLYTRQRYY-NH 2 、 Compound 124 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-APE-OEG2-QRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 125 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PGEDASPEELQRYYYVSLRYHYYNYWWATQRYY-NH 2 、 Compound 126 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PEDSSPELQRYYYVSLHRHYYNYNWLTRQRYY-NH 2 、 Compound 127 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PEEDA-SAS-QRYYYVS-L-RHYYNYN-W-L-T-R-QRYY-NH 2 、 Compound 128 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDAPAPAEAEGIQRYYYVSLRHYYYYNWLTRQRYYY-NH 2 、 Compound 129 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYYTALENE 2 、 Compound 131 iVal-APE (C18DA-gGlu-OEG1-OEG2-) AEEGDA-QRYYYVHYYNWWLTRQRYY-NH 2 、 Compound 132 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQKHYYYYVTLRHYYYYNYWWLTRQRY-NH 2 、 Compound 133 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDAQRYYYVHYYNYNWWLTRQRYY-NH 2 、 Compound 134 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SPEEDA-QRYYYYT-YLHYYYNWWLTRQRYY-NW 2 、 Compound 135 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEADASPEELQRYYYVHYYNYNYWWLTRQRYY-NH 2 、 Compound 136 iVal-AEK(318DA-gllu-E･11m-･.EASSPEEQQRYYS,,R(YMMMMMMMMH 2 、 Compound 137 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYVSLRYHYYNYWWITRQRYY-NH 2 、 Compound 138 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQQYYYYVSLLRHYYYYNNWLTRQRY-NH 2 、 Compound 139 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEG-QRYYYVSLRHYYNYNWLTRQRYY-NH 2 、 Compound 140 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PGEDASQYYYYVSLRHYYYYNWLTRQRY-NH 2 、 Compound 141 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEAASPEEAQRYYYVSARHYYNYNWLRTQRYY-NH 2 、 Compound 142 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PPY-ASPE-QRYYYVS-LHRHYYNYNW-LTRQRYY-NH 2 、 Compound 143 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDATPPEEDAQRYYYVXALRHYYNWWLTRQRYY-NH 2 、 Compound 144 iVal-APE (C18DA-gGlu-OEG1-OEG2-) AEEGDA-SPE-EQ-YYYYV-SLR-HYYYYNNW-LTR-QRY-NH 2 、 Compound 145 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDSSPUEQRYYYVSLRHYYNYNWLLRHQRYY-NH 2 、 Compound 146 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASPE-QRYYYVST-RHYYNYNW-L-T-R-QRYY-NH 2 、 Compound 147 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQKHYYYYVSLRHYYYYNYWWLTRQRY-NH 2 、 Compound 148 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDAPAPAQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 149 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEAASPEEAQRYYYYYVHYYYYNYWWLTRQRYYY-NH 2 、 Compound 150 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-OEG 2 、 Compound 151 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEA-E-A-S-P-E-R 2 、 Compound 152 iVal-APE (C18DA-gGlu-OEG1-OEG2-) AEEGDA-ASPEE-QRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 154 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASP-QRY-YES-VS-L-R-H-Y-N-W-L-T-R-QRY-N-H 2 、 Compound 155 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 156 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SEQYYYYVSLRHYYYYNNWLTRQRY-NH 2 、 Compound 157 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PEEDASPEETQRYYYVSLRHYYNYNWLTRQRYYY-NH 2 、 Compound 158 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYVSLRYHYWNYYLTRQRYY-NH 2 、 Compound 159 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEADASPEEGQYYYYVSLRHYYYYNWLTRQRY-NH 2 、 Compound 160 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEADAQRYYYTDSLRHYYNYNWLQRYY-NH 2 、 Compound 161 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-PEDQQYYYYVSLRHYYYYNWLTRQRY-NH 2 、 Compound 162 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYEHVSLRYYYNWWLTRQRYY-NH 2 、 Compound 163 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEAASPEEAQRYYYYYVHYYYYNYWWLTRQRYYY-NH 2 、 Compound 164 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SEQ-YYYV-S-L-R-H-YYYN-W-L-T-R-Q-R-Y-N-W 2 、 Compound 165 iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDASPEELQRYQVSLRHYYNWLTRQRY-NH 2 、 Compound 166 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PPA-DA-SP-QR-Y-Y-V-H-Y-Y-N-W-L-T-R-Q-R-Y-N-H 2 、 Compound 167 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQQYEHVSLLRHYYYNWWLTRQRY-NH 2 、 Compound 168 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-QRYYYVSLRHYYYNWWITRQRYY-NH 2 、 Compound 169 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASP-QRYYYV-A-L-R-H-Y-N-W-L-T-R-QRY-N-H 2 、 Compound 170 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASPE-QYYYVS-LHRHYYNYNW-LTRQRY-NH 2 、 Compound 171 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-TPEEDA-QRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 172 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-PEDQRYYYVXA-RHYYYNWWLTRQRYY-NH 2 、 Compound 173 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYVHYYNYNYWWLTRQRYY-NH 2 、 Compound 174 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PEEDA-PEDQRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 175 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-APE-QRYYYVHYYNWWLTRQRYY-NH 2 、 Compound 176 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASEQQRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 177 iVal-APEK(C18DA-gGlu-OEG1-OEG2-)PEEDSSPEELQRYYVELRHYYNWLTRQRY-NH 2 、 Compound 178 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDATPEEDETRYYYYYVSLLRHYYYYYYWWLTRQRY-NH 2 、 Compound 180 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQQYYYYVSLRHYYYYNWLTRQRY-NH 2 、 Compound 181 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEADASPEEQRYYYVHYYNYNWLTRQRYY-NH 2 、 Compound 182 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEGDGSPEEGQRYYYVHYYYNWWLTRQRYY-NH 2 、 Compound 183 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PPEDASPEDQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 184 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEAASPEEAQRYYYYYVTLRHYYYYNYWWLTRQRYYY-NH 2 、 Compound 185 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASP-QRYYYVH-YYYNYNW-LTR-QRYY-NH 2 、 Compound 186 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SASQR-R-Y-Y-V-H-Y-Y-N-W-L-T-R-Q-R-Y-N-H 2 、 Compound 188 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-OEG 2 、 Compound 189 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASEAELQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 190 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-APE-QRY-Y-V-S-L-R-H-Y-N-W-L-T-R-QRY-N-H 2 、 Compound 191 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYISHYSLRHYYNYNWLTRQRYY-NH 2 、 Compound 192 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDAAPA-A-E-LQRYYYVS-L-RHYYNYNW-L-T-R-QRYY-NH 2 、 Compound 193 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASEEGIQRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 195 iVal-AEK(318DA-gllu-E･11m-･The 2 、 Compound 196 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PPEDA-QRYYYVSLRHYYNWWLTRQRYY-NH 2 Compound 198 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-PEEDALQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 199 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-PEEDQRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 200 iVal-APE (C18DA-gGlu-OEG1-OEG2-)Hype-Ed-A-S-P-E-R 2 、 Compound 201 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PQXEDA-OEG1-OEG2-)PQXEDA-OEG1-OEG2-)PQXEYA 2 、 Compound 202 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-APE-QKHYYYYVSLRHYYYYNNWLTRQRY-NH 2 、 Compound 203 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 204 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASPEE-QRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 205 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASP-PEE-QKH-YYYYYV-S-L-R-H-YYYNYW-W-L-T-R-Q-R-Y-N-H 2 、 Compound 206 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQYEHYVSLLRHYYYNWWLTRQRY-NH 2 、 Compound 208 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASEETQRYYYVSLRYHYYNYNWLTRQRYY-NH 2 、 Compound 209 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDSPEEDSPEEDSQRYYYVSLRHYYNYNWLTRQRYY-NH 2 、 Compound 211 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDATAQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 214 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASEQQRYYYVXALRHYYNWWLTRQRYY-NH 2 、 Compound 215 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPASPAQRYYYYYVHYYYYNYWWLTRQRYYY-NH 2 、 Compound 216 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQYYYYVSLLRHYYYYNWLTRQRY-NH 2 、 Compound 217 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPAESPAELQRYYYYYVYALYYYYYNYWWLTRQRYYY-NH 2 、 Compound 218 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEDSSPELQRYYYVXYLHYYNWWLTRQRYY-NH 2 、 Compound 219 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEGA-APEEGA-QRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 220 iVal-APE(C18DA-gGlu-OEG1-OEG2-)PEEAASAEAEELQRYYYVSLRHYYNYNWLLTRQRYY-NH 2 、 Compound 221 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDAPAMEEEL 2 、 Compound 222 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SAE-EEG-QQYYYYV-S-L-R-H-YYYNYW-W-L-T-R-Q-R-Y-N-H 2 、 Compound 223 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEAAEAEPEEAQRYYYYYVSLRHYYYYNYWWLTRQRYYY-NH 2 、 Compound 224 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PGE-E-A-S-P-E-R 2 、 Compound 225 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PGEDA-EGPEDQYYYYVSLRHYYYYNWLTRQRY-NH 2 、 Compound 226 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEAASPEETQRYYYVSLRHYYNYNWLTRQRYYY-NH 2 、 Compound 227 iVal-APE (C18DA-gGlu-OEG1-OEG2-) AEEGDA-SPE-QYYYYVSLRHYYYYNWLTRQRY-NH 2 、 Compound 228 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQQYYYYVSLLRAYYYYYNNWLTRQRY-NH 2 、 Compound 229 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDQRYYYVSARHYYNYNWLTRQRYY-NH 2 、 Compound 230 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEQRYYYYYVXYYYYYYWWWLTRQRYYY-NH 2 、 Compound 231 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-PEDQKHYYYYVSLRHYYYYNNWLTRQRY-NH 2 、 Compound 232 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PPEDASPEDQRYYYVHYYNYNYWWLTRQRYY-NH 2 、 Compound 233 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEAASPEEAQQYYYYVSLRHYYYYNWLTRQRY-NH 2 、 Compound 234 iVal-APAK (C18DA-gGlu-OEG1-OEG2-)PEE-ASPEE-QRYYYVS-L-R-H-Y-N-W-L-T-R-QRYY-N-H 2 、 Compound 235 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASHypEELQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 236 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEGAPQRYYYVSLRHYYNWWLTRQRYY-NH 2 、 Compound 237 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEEEDAQRYYYVHRYYYNWWLTRQRYY-NH 2 、 Compound 239 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-SEQ-RXRY-HYYYNYNW-LXTR-QRY-N 2 、 Compound 240 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDASPEAQRYYYVSLRYHYYNWWLTRQRYY-NH 2 、 Compound 241 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASP-PEE-QRY-Y-V-S-L-R-H-Y-N-W-L-T-R-QRY-N-H 2 、 Compound 242 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEADASAQRYYYYYVSLRHYYYYNYWWLTRQRYYY-NH 2 、 Compound 243 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEE-ASPEE-QQYYYYVS-LHRHYYYYNW-LTRQRY-NH 2 、 and, Compound 244 iVal-APE (C18DA-gGlu-OEG1-OEG2-)PEEDA-EGP-QRYYYVS-LHRHYYNYNW-LTRQRYY-NH 2 、 (Wherein, all iVal are 3-methylbutanoyl (—C(O)CH 2 CH (CH 3 ) 2 ) represents 2. The PYY analog of claim 1, which is a compound selected from the group consisting of:

4. The PYY analogue of any one of claims 1 to 3, in the form of a salt.

5. The following compounds: (Compound 14) or a pharmaceutically acceptable salt thereof.

6. The following compounds: (Compound 23) or a pharmaceutically acceptable salt thereof.

7. The following compounds: (Compound 53) or a pharmaceutically acceptable salt thereof.

8. The following compounds: (Compound 74) or a pharmaceutically acceptable salt thereof.

9. The following compounds: (Compound 106) or a pharmaceutically acceptable salt thereof.

10. The following compounds: (Compound 117) or a pharmaceutically acceptable salt thereof.

11. The following compounds: (Compound 135) or a pharmaceutically acceptable salt thereof.

12. The following compounds: (Compound 171) or a pharmaceutically acceptable salt thereof.

13. The following compounds: (Compound 230) or a pharmaceutically acceptable salt thereof.

14. The following compounds: (Compound 231) or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition comprising at least one PYY analogue according to any one of claims 1 to 14.

16. 16. A pharmaceutical composition according to claim 15 for use in the treatment of a condition or disease associated with or caused by excess weight or excessive weight gain.

17. 17. A pharmaceutical composition according to claim 15 or 16 for use in the treatment of obesity or an obesity-related condition.

18. 17. The pharmaceutical composition of claim 15 or 16 for use in the treatment of atherogenic dyslipidemia, fatty liver, NAFLD, NASH, renal failure, or atherosclerosis.

19. 19. The pharmaceutical composition of any one of claims 15 to 18, administered as part of a combination therapy with an agent for the treatment of diabetes, obesity, dyslipidemia, or hypertension.

20. 19. The pharmaceutical composition of any one of claims 15 to 18, which is administered as part of a combination therapy together with an agent for the treatment of obesity, wherein said agent for obesity is a GIP or GLP-1 receptor agonist, exendin-4 or an exendin-4 analogue, any other GLP-1 receptor agonist including liraglutide, semaglutide, dulaglutide, or albiglutide, or a glucagon-GLP-1 dual agonist, a GLP-1 / GIP dual agonist, or a GLP-1 / GIP / glucagon triple agonist, or an amylin receptor agonist.

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