Saccharide-based conjugates for RNA delivery and therapy

Abstract

The present disclosure provides Saccharide-Based Ligands of Formula (A): and related compounds and conjugates, and pharmaceutically acceptable salts and stereoisomers thereof. The present disclosure also relates to uses of the compounds and conjugates, e.g., in delivering oligonucleotides and / or treating or preventing diseases.

Description

SACCHAREDE-BASED CONJUGATES FOR RNA DELIVERY AND THERAPYRELATED APPLICATION

[0001] This application claims priority to, and the benefit of, U.S. Application No. 63 / 677,559, filed on July 31, 2024, the entire contents of which are incorporated herein by reference.INCORPORATION OF THE. SEQUENCE LISTING

[0002] This application incorporates by reference in its entirety a Sequence Listing in electronic format submitted with this application, entitled 02171 WO_CRF_sequencelisting.xml, created on July 30, 2025, and is 522,253 bytes in size.BACKGROUND

[0003] Oligonucleotide-based therapeutics have received regulatory approvals from the FDA and have been used as an effective means to modulate disease-related gene expression However, a major obstacle preventing its further clinical application is the lack of an effective delivery’ approach to direct oligonucleotides to extrahepatic tissues or cell types other than liver hepatocytes. Therefore, there remains a need in the art for approaches to efficiently and specifically deliver oligonucleotide to extrahepatic tissues or cell types.

[0004] Saccharides have been explored as targeting ligands to facilitate oligonucleotide delivery', with the best-demonstrated case of N-acetyl galactosamine (GalNAc) for the delivery of oligonucleotide to liver hepatocytes. A variety of other types of saccharide moieties have also been tested for extrahepatic delivery, but their delivery efficiency and specificity are generally met with limited success as drug development candidates.

[0005] The present disclosure addresses this need by designing oligonucleotide conjugates with natural or modified saccharide moieties to enhance the delivery and cellular uptake of oligonucleotide in macrophage cells in liver and other tissues.SUMMARY

[0006] In some aspects, the present disclosure provides a Saccharide-Based Ligand (i.e., variable L) comprising at least one saccharide moiety.

[0007] In some aspects, the present disclosure provides a Saccharide-Based Ligand Scaffold being a compound of Formula (AA’):or a pharmaceutically acceptable salt thereof, wherein:L comprises at least one saccharide moiety;REis -ORE1, -N(RE2)2, or -C(RE3)3,RE1is H, -C; O alkyl), C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, or a hydroxy protecting group, wherein the -C(=O)-( C1-C6alkyl), C1-C6alkyl, C2-C6alkenyl, or C2-C6alkynyl is optionally substituted with one or more halogen; each RE2is independently H, -C(=O)-(C1-C6alkyl), C1-C6, alkyl, C2-C6alkenyl, C2-C6alkynyl, or an amino protecting group, wherein the -C(=O)-( C1-C6alkyl), C1-C6alkyl, C2-C6alkenyl, or C2-C6alkynyl is optionally substituted with one or more halogen; and each RE3is independently II, halogen, -C(=O)-(C1-C6alkyl), C1-C6alkyl, C2-C6alkenyl, or C2-C6. alkynyl, wherein the -C(=0)-( C1-C6alkyl), C1-C6alkyl, C2-C6alkenyl, or C2-C6alkynyl is optionally substituted with one or more halogen.

[0008] In some aspects, the present disclosure provides a conjugate or a pharmaceutically acceptable salt thereof, comprising:(i) one or more Nucleic Acid Agent; and(ii) one or more Saccharide-Based Ligand, each independently being L, wherein L comprises at least one saccharide moiety.

[0009] In some aspects, the present disclosure provides a Saccharide-Based Ligand Agent being a compound of Formula (I), (II), (III), or (IV):or a pharmaceutically acceptable salt thereof, wherein:L comprises at least one saccharide moiety,B is H, C1-C6alkyl, or a nucleobase moiety;V is -NR'''-, or -C(R' )2-; each R' independently is H or C1-C6alkyl optionally substituted with one or more halogen;X is H, halogen, or -ORX;Rxis H, Cj-Cs alkyl, or -(C1-C6, alkyl)-(C6-Cjo aryl), wherein the C1-C6, alkyl or -(C1-C6alkyl)-(C6-Cio aryl) is optionally substituted with one or more RXa; or Rxand R4together form C1-C6alkylene; each RAaindependently is halogen, Ci-CY alkyl, or -O-(C1-C6alkyl), wherein the C1-C6alkyl or -O-(C1-C6alkyl) is optionally substituted with one or more halogen;Y is H, Ci-Cb alkyl optionally substituted with one or more halogen, -P(RY)?, - P(ORY)( N(RY)2), -P(=O)(ORY)RY, -P(-S)(ORY)RY, -P(==O)(SRY)RY, -P(-S)(SRY)RY, - P(=O)(OR'1)z, -P(=S)(ORY)2, -P(=OXSRY)2, -P(=S)(SRY)2, or a hydroxy protecting group; each Ryindependently is H or C1-C6alkyl optionally substituted with one or more halogen or cyano;Z is II, Ci-CY alkyl optionally substituted with one or more halogen, -P(RZ)2, - P(0RZ)(N(RZ)2), -P(=O)(ORZ)RZ, -P(=S)(ORZ)RZ, -P(=O)(SRZ)RZ, -P(=S)(SRZ)RZ, - P(=O)(ORZ)2, -P(=S)(ORZ)2, -P(=O)(SRZ')2, -P(=S)(SRZ)2, or a hydroxy protecting group, each R2independently is H or Ci-C* alkyl optionally substituted with one or more halogen or cyano; or Y and Z in Formula (I) or (III), together form -Si(RL”)2-O-Si(RL")2~, wherein each RL"independently is H or C1-C6alkyl;each Raindependently is H, halogen, or Ci-C<5 alkyl optionally substituted with one or more halogen; or two vicinal Raform a bond;R1is H, halogen, or C,1a-lCk6yl optionally substituted with one or more halogen;R2is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen,R’ is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen;R4is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen; or R4and Rxtogether form C1-C6alkylene; each R~ independently is H, halogen, or C1-C6, alkyl optionally substituted with one or more halogen; and n is an integer ranging from 0 to about 10.

[0010] In some aspects, the present disclosure provides a conjugate or a pharmaceutically acceptable salt thereof, comprising:(i) one or more Nucleic Acid Agent; and(ii) one or more Saccharide-Based Ligand Unit, wherein each Saccharide-Based Ligand Unit independently is:wherein: variables L, B, V, X, Ra, n, Rv, Rx, RXa, Rv, Rz, R1, R2, R3, R4, and R5are described herein; andwhen the Saccharide-Based Ligand Unit is at the 3 ’-terminus of the Nucleic Acid Agent,# is an attachment to the rest of the conjugate; and## is H, Ci alkyl optionally substituted with one or more halogen, -P(RY)2, - P(ORYXN(Ry)2), -P(=O)(ORY)RY, -P(=S)(ORY)RY, -P(=O)(SRY)RY, -P(=S)(SRY)RY- P(::;:0)(0R^)2, -IK S)(()R ‘ p, -P( O K SR '' )2. -P(=:S)(SRI)2, or a hydroxy protecting group, or when the Saccharide-Based Ligand Unit is at the 5’-termmus of the Nucleic Acid Agent,# is H, -P(RZ)2, -P(ORZ)(N(RZ)2), -P(-O)(ORZ)RZ, -P(===S)(ORzjRz, -P(-O)(SRZ)RZ, - P(:;;S)(SRZ)RZ, -P( ())( ( )R . -P(-S)(ORZ)2, -P(-O)(SRZ)2, -P( SKSR' )?. or a hydroxy protecting group; and## is an attachment to the rest of the conjugate; or each of # and ##- independently is an attachment to the rest of the conjugate.

[0011] In some aspects, the present disclosure provides an isotopic derivative of a compound (e.g., Saccharide-Based Ligand, Saccharide-Based Ligand Agent, or Saccharide-Based Ligand Scaffold), or conjugate described herein

[0012] In some aspects, the present disclosure provides a pharmaceutical composition comprising a compound (e.g., Saccharide-Based Ligand, Saccharide-Based Ligand Agent, or Saccharide-Based Ligand Scaffold) or conjugate described herein.

[0013] In some aspects, the present disclosure provides a method of modulating the expression of a target gene in a subject, comprising administering to the subject a conjugate descri bed herein

[0014] In some aspects, the present disclosure provides a method of delivering a Nucleic Acid Agent to a subject comprising administering to the subject a conjugate described herein.

[0015] In some aspects, the present disclosure provides a method of treating or preventing a disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a conjugate described herein.

[0016] In some aspects, the present disclosure provides a conjugate described herein for modulating the expression of a target gene in a subject.

[0017] In some aspects, the present disclosure provides a conjugate described herein for delivering a Nucleic Acid Agent to a subject.

[0018] In some aspects, the present disclosure provides a conjugate described herein for treating or preventing a disease in a subject in need thereof

[0019] In some aspects, the present disclosure provides a use of a conjugate described herein in the manufacture of a medicament for modulating the expression of a target gene in a subject.

[0020] In some aspects, the present disclosure provides a use of a conjugate described herein in the manufacture of a medicament for delivering a Nucleic Acid Agent to a subject.

[0021] In some aspects, the present disclosure provides a use of a conjugate described herein in the manufacture of a medicament for treating or preventing a disease in a subject in need thereof.

[0022] In some aspects, the present disclosure provides a compound being an isotopic derivative of a compound (e.g., Saccharide-Based Ligand, Saccharide-Based Ligand Agent, or Saccharide- Based Ligand Scaffold) described herein.

[0023] In some aspects, the present disclosure provides a conjugate being an isotopic derivative of a conjugate described herein.

[0024] In some aspects, the present disclosure provides a pharmaceutical composition comprising a conjugate described herein.

[0025] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In the specification, the singular forms also include the plural unless the context clearly dictates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. All publications, patent applications, patents and other references mentioned herein are incorporated by reference The references cited herein are not admitted to be prior art to the claimed invention. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods and examples are illustrative only and are not intended to be limiting Tn the case of conflict between the chemical structures and names of the compounds disclosed herein, the chemical structures wall control.

[0026] Other features and advantages of the disclosure wall be apparent from the following detailed description and claims.BRIEF DESCRIPTION OF THE FIGURES

[0027] FIG, 1 shows the gene silencing activity of siRNA duplexes in liver of C57 / B6 male mice on day 7 after a single 3 mg / kg s.c. injection.

[0028] FIG, 2 shows siRNA duplex uptake in liver of C57 / B6 male mice on day 7 after a single 3 mg / kg s.c. injection.

[0029] FIG. 3 shows the gene silencing activity of siRNA duplexes in liver of C57 / B6 male mice on day 7 after a single 1 mg / kg, 3 mg / kg, or lOmg / kg s.c. injection.

[0030] FIG. 4 shows the uptake of siRNA duplexes in liver of C57 / B6 male mice on day 7 after a single Img / kg, 3 mg / kg, or lOmg / kg s.c. injection.

[0031] FIGS. 5A-5E show the gene silencing activity of siRNA duplexes in liver, kidney, spleen, intestine, and gWAT, respectively, of C57ZB6 male mice on day 7 after a single 1 mg / kg or 3 mg / kg s.c. injection.

[0032] FIG. 6 shows exemplary conjugation configurations of Saccharide-Based Ligand Units or Saccharide-Based Ligands (i.e., variable L), and a Nucleic Acid Agent. Note, if the Nucleic Acid Agent comprises more than one strand, then the atachment of the Saccharide-Based Ligand Unit(s) or Saccharide-Based Ligand(s), either directly or indirectly (e.g., through Linker Unit(s)), may be to one or both strands of the Nucleic Acid Agent (e.g., sense and / or antisense strand).DETAILED DESCRIPTION

[0033] Oligonucleotide-based therapeutics require efficient and specific delivery to target disease-related tissues or ceil types and to regulate disease-related gene expression. One method of achieving specific targeting is to conjugate a targeting moiety to the nucleic acid (e.g., oligonucleotide). The targeting moiety may help direct the nucleic acid to the site of interest and facilitate the internalization of oligonucleotides.

[0034] The present disclosure provides Saccharide-Based Ligands (i.e., variable L), Saccharide- Based Ligand Units, and compounds (e.g., Saccharide-Based Ligand Agents and Saccharide- Based Ligand Scaffolds), which may improve the targeted delivery' efficiency of oligonucleotides to macrophage cells in liver and other tissues, resulting in improved potency in regulating target genes. The present disclosure also provides oligonucleotide conjugates described including the Saccharide-Based Ligand Units and / or Saccharide-Based Ligands. The oligonucleotide conjugates comprising Saccharide-Based Ligand Units and / or Saccharide-Based Ligands may demonstrate enhanced cellular uptake efficiency, delivery efficiency and specificity, and stronger RNAi activities in macrophage cells than oligonucleotides without theSaccharide-Based Ligand Units and / or Saccharide-Based Ligands. The macrophage cells could be in, e.g., liver, kidney, spleen, and other tissues.Saccharide-Based Ligand Agents, Saccharide- Based Ligand Scaffolds, and Saccharide- Based Ligands

[0035] In some aspects, the present disclosure provides a Saccharide-Based Ligand (i.e., variable L) comprising at least one saccharide moiety.

[0036] In some aspects, the present disclosure provides a Saccharide-Based Ligand Scaffold being a compound of Formula (AA’):or a pharmaceutically acceptable salt thereof, wherein:L comprises at least one saccharide moiety,REis -OREl, -N(RE2)2, or -C(RE3>;RE1is H, -C(=O)~(C1-C6alkyl), C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, or a hydroxy protecting group, wherein the -C(=O)-(C1-C6alkyl), C1-C6alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more halogen; each Rt2is independently H, -C(:=:O)-(Ci -Ce alkyl), C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl, or an amino protecting group, wherein the -C(=O)-(C1-C6alkyl), C1-C6alkyl, C2-C6 alkenyl, or C2-C6alkynyl is optionally substituted with one or more halogen; and each RE3is independently H, halogen, -C(=O)-(Ct-C6 alkyl), C1-C6alkyl, Cr-Ce alkenyl, or C2-C0 alkynyl, wherein the -C(=O)-(C1-C6alkyl), C1-C6. alkyl, C2-C6alkenyl, or alkynyl C2-C6is optionally substituted with one or more halogen.

[0037] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound is of Formula (AA),or a pharmaceutically acceptable salt thereof, wherein variables E, Rr, Lf, W, SA, ml, p l , and q are described herein.

[0038] In some aspects, the present disclosure provides a conjugate or a pharmaceutically acceptable salt thereof, comprising:(i) one or more Nucleic Acid Agent; and(ii) one or more Saccharide-Based Ligand, each independently being L, wherein L comprises at [east one saccharide moiety.

[0039] In some embodiments, the present disclosure provides a conjugate or a pharmaceutically acceptable salt thereof, comprising:(i) one or more Nucleic Acid Agent; and(ii) one or more Saccharide-Based Ligand, each independently being L of Formula (A):wherein :E is O or S,q is 1, 2, or 3, each R'* is independently H, halogen, or Ci-C-6 alkyl optionally substituted with one or more halogen; each SA is independently a saccharide moiety; andindicates the point of attachment to the rest of the conjugate.

[0040] In some aspects, the present disclosure provides a Saccharide-Based Ligand Agent being a compound of Formula (I), (II), (III), or (IV):or a pharmaceutically acceptable salt thereof, wherein:L comprises at least one saccharide moiety,B is H, CI-CA alkyl, or a nucleobase moiety;V is -O-, -NR\ or -CfR? )2~; each R' independently is H or C1-C6alkyl optionally substituted with one or more halogen;X is H, halogen, or -OR \Rxis H, Cj-Cs alkyl, or -(C1-C6, alkyl)-(C6-Cio aryl), wherein the C1-C6alkyl or -(Ci-C* alkyl)-(C6-Cio aryl) is optionally substituted with one or more RXa; or RAand R4together form Ci-Cc, alkylene; each RAaindependently is halogen, Ci-Cg alkyl, or -O-(C1-C6alkyl), wherein the C1-C6alkyl or -O-(C1-C6alkyl) is optionally substituted with one or more halogen;Y is H, C1-C6alkyl optionally substituted with one or more halogen, -P(RY)2, - P(ORYXN(RY)2), -P(=O)(ORY)RY, -P(=S)(ORY)RY, -P(=O)(SRY)RY, -P(=S)(SRY)RY, - P(=O)(OR'!)2, -P(::::S)(ORY)2, ~P(=O)(SRY)2, -P(::::S)(SRY)2, or a hydroxy protecting group,each R' independently is H or C1-C6alkyl optionally substituted with one or more halogen or cyano;each Raindependently is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen; or two vicinal Raform a bond;R1is H, halogen, or C1-C& alkyl optionally substituted with one or more halogen; R’ is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen, R’ is H, halogen, or Ci-Ck alkyl optionally substituted with one or more halogen;R4is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen; or R4and Rxtogether form Ci-CR alkylene; each R5independently is H, halogen, or , alkylC op1-tCi6onally substituted with one or more halogen; and n is an integer ranging from 0 to about 10.

[0041] It is understood that, for a compound / moiety of the present disclosure (e.g., agent, unit, and conjugate), variables #, ##, E, Lf, L2, W, SA, ml, m2, pl, m2, q, L, RL, RL1, R’ , R1’, R2’, R3’, R4’, R5’, Ra>, Rla, R2a, R3a, R4a, R5a, RE, RE1, RE2, RE3, B, V, RU3’, Rv, X, Rw, Rx, RXa, Y, R\ Z, RZ, Ra, R1, R2, R3, R4, R5, and n can each be, -where applicable, selected from the groups described herein, and any group described herein for any of variables #, ##, E, L1, L2, W, SA, m l, m2, pl , m2, q, L, RL, RL1, RfZ, R1’, R2’, R3’, R4’, R5’, R3’, Rla, R2a, R3a, R4a, R5a, RE, REl, RE2, RE3, B, V, RU3‘, RV, X, Rw, Rx, RXa, Y, RY, Z, Rz, Ra, R1, R2, R3. R4, R5, and n can be combined, where applicable, with any group described herein for one or more of the remainder of variables #, ##, E, L1, L2, W, SA, nil, m2, pl, m2, q, L, RL, RIJ, RL, R1’, R2’, R3’, R4’, R5’, Ra’, Rla, R2a, R33, R4a, R5a, RE, RE1, RE2, RE3, B, V, RU3’, Rv, X, Rw, Rx, RXa, Y, RY, Z, Rz, Ra, R1, R2, R3, R4, R5, and n.Variables L, RL, RL’, R1R2’, R3’ R4’, R5R° R!a, R2i\ R3a, R4a, andR5a

[0042] In some embodiments, L is a Saccharide-Based Ligand.

[0043] In some embodiments, L comprises at least one saccharide (e.g, monosaccharide, disaccharide, or polysaccharide) moiety or derivative thereof. In some embodiments, L comprises at least one mannose (e.g, monomannose, dimannose, or polymannose) moiety or derivative thereof. In some embodiments, L comprises at least one fucose (e.g., monofucose, difucose, or polyfucose) moiety or derivative thereof.

[0044] In some embodiments, L comprises at least one monosaccharide moiety or derivative thereof. In some embodiments, L comprises at least one disaccharide moiety or derivative thereof. In some embodiments, L comprises at least one polysaccharide moiety or derivative thereof.

[0045] In some embodiments, L comprises at least one monomannose moiety or derivative thereof. In some embodiments, L comprises at least one dimannose moiety or derivative thereof. In some embodiments, L comprises at least one polymannose moiety or derivative thereof.

[0046] In some embodiments, L comprises at least one monofucose moiety or derivative thereof. In some embodiments, L comprises at least one difucose moiety or derivative thereof. In some embodiments, L comprises at least one polyfucose moiety or derivative thereof.

[0047] In some embodiments, L comprises one, two, or three saccharide (e.g., monosaccharide, disaccharide, or polysaccharide) moi eties. In some embodiments, L comprises one saccharide (e.g., monosaccharide, di saccharide or polysaccharide) moiety. In some embodiments, I. comprises two saccharide (e.g, monosaccharide, disaccharide or polysaccharide) moieties. In some embodiments, L comprises three saccharide (e.g., monosaccharide, disaccharide or polysaccharide) moieties.

[0048] In some embodiments, L comprises one, two, or three mannose (e.g., monomannose, dimannose, or polymannose) moieties. In some embodiments, L comprises one mannose (e.g., monomannose, dimannose, or polymannose) moiety. In some embodiments, L comprises two mannose (e.g., monomannose, dimannose, or polymannose) moieties. In some embodiments, L comprises three mannose (e.g., monomannose, dimannose, or polymannose) moieties.

[0049] In some embodiments, L comprises one, two, or three fucose (e.g., monofucose, difucose, or polyfucose) moieties. In some embodiments, L comprises one fucose (e.g.,monofucose, di fucose, or polyfucose) moiety. In some embodiments, L comprises two fucose (e.g., monofucose, difucose, or polyfucose) moieties. In some embodiments, L comprises three fucose (e.g., monofucose, difucose, or polyfucose) moieties.

[0050] In some embodiments, L is -C(=O)RLor-C(=S)RL, wherein:hydrocarbon chain, wherein the C2-C20 hydrocarbon chain or 2- to 20-membered heterohydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more RL.

[0055] In some embodiments, RLis C50-C100 hydrocarbon chain or 50- to 100-membered hetero-hydrocarbon chain, wherein the C50-C100 hydrocarbon chain or 50- to 100-memberedhetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more RL.

[0056] In some embodiments, RLis a C2-C19 hydrocarbon chain, a C2-C18 hydrocarbon chain, a C2-C17 hydrocarbon chain, a C2-C16 hydrocarbon chain, a C2-C15 hydrocarbon chain, a C2-C14 hydrocarbon chain, a C2-C13 hydrocarbon chain, a C2-C12 hydrocarbon chain, a C2-C11 hydrocarbon chain, a CS-CJO hydrocarbon chain, a C2-C9 hydrocarbon chain, a C2-C8 hydrocarbon chain, a C2-C7 hydrocarbon chain, a C2-C6hydrocarbon chain, a C2-C5 hydrocarbon chain, a C2-C6hydrocarbon chain, or a C2-C3 hydrocarbon chain, wherein the hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted with one or more Pd

[0057] In some embodiments, RLis a C3-C20 hydrocarbon chain, a C4-C20 hydrocarbon chain, a C5-C20 hydrocarbon chain, a C6-C20 hydrocarbon chain, a C7-C20 hydrocarbon chain, a Cg-Cro hydrocarbon chain, a C9-C20 hydrocarbon chain, a C10-C20 hydrocarbon chain, a C11-C20 hydrocarbon chain, a C12-C20 hydrocarbon chain, a C13-C20 hydrocarbon chain, a C14-C20 hydrocarbon chain, a C15-C20 hydrocarbon chain, a C16-C20 hydrocarbon chain, a C17-C20 hydrocarbon chain, a C18-C20 hydrocarbon chain, or a C19-C20 hydrocarbon chain, wherein the hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more RL.

[0058] In some embodiments, RLis a C3-C19 hydrocarbon chain, a C4-C18 hydrocarbon chain, a Cs-Cj7 hydrocarbon chain, a C6-C16 hydrocarbon chain, a C7-C15 hydrocarbon chain, a C«-Ci4 hydrocarbon chain, a C9-C13 hydrocarbon chain, or a C10-C12 hydrocarbon chain, wherein the hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more RL.

[0059] In some embodiments, RLis a C50-C99 hydrocarbon chain, a C50-C98 hydrocarbon chain,

[0060] In some embodiments, Rbis a Csi-Cioo hydrocarbon chain, a Csz-Csoo hydrocarbon

[0061] In some embodiments, REis a C51-C99 hydrocarbon chain, a C52-C98 hydrocarbon chain, a C53-C97 hydrocarbon chain, a C54-C96 hydrocarbon chain, a C55-C95 hydrocarbon chain, a C56-

[0062] In some embodiments, RLis a C2 hydrocarbon chain substituted with at least onesubstituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis a C17 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis a Cis hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a C19 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, Rijis a C20 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, Rfis a C21 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:. In some embodiments, RLis a C22 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a C23 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a C24 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a C2.5 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R1is a C26 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, RLis a C27 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!. In some embodiments, R1is a C28 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a C29 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R:is a C30 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, Rbis a C31 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1’. In some embodiments, RLis a C32 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a C33 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, RLis a C34 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a C35 hydrocarbon chain substituted with at least one saccharide moiety and optionallysubstituted with one or more RL. tn some embodiments, RLis a C36 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1’. In some embodiments, RLis a C37 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a C39 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1' is a C40 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a Chi hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R! / . In some embodiments, R1is a C42 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Ru’. In some embodiments, RLis a C43 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a C44 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RJIn some embodiments, RLis a C45 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, RLis a C46 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rd . In some embodiments, RLis a C47 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1-’. In some embodiments, RLis a C48 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis a C49 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis a C50 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis a C52 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R" . In some embodiments, RLis a C53 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a C54 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments,RLis a C55 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a C56 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a C57 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:' . In some embodiments, RLis a Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a C59 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rl. In some embodiments, Rris a Cf,o hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis a Cei hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis a Cs2 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a Ce.s hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, Rfis a Cs4 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1,. In some embodiments, R;is a C-65 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a Cc,6 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1-’. In some embodiments, RLis a C.57 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL\ In some embodiments, RLis a Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a C09 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R5In some embodiments, RLis a C70 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a C71 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:. In some embodiments, RLis a (>2 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, R1is a C73 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!. In some embodiments, R1is a C74 hydrocarbon chain substituted with at leastone saccharide moiety and optionally substituted with one or more RLin some embodiments, Rbis a C75 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a C76 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rij. In some embodiments, RLis a C77 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R1is a C78 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a C79 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a Cso hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis a Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis a Cs?. hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R' . In some embodiments, RLis a Cs3 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a CM hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1’. In some embodiments, R1' is a Cse hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1-'. In some embodiments, RLis a Cs7 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, RLis a Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rv. In some embodiments, RLis a Cs9 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1' is a C90 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a C91 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, R1is a C92 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a C93 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted withone or more RL. In some embodiments, RLis a C94 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a C95 hydrocarbon chain substituted with at (east one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a C96 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a C97 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or moreIn some embodiments, RLis a C98 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a C99 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R!is a CJOO hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL.

[0063] In some embodiments, R1' is a linear saturated hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL".

[0064] In some embodiments, RLis a branched saturated hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' .

[0065] In some embodiments, R1' is a saturated C2-C19 hydrocarbon chain, a saturated C2-C18 hydrocarbon chain, a saturated C2-C17 hydrocarbon chain, a saturated C2-C16 hydrocarbon chain, a saturated C2-C15 hydrocarbon chain, a saturated C2-C14 hydrocarbon chain, a saturated C2-C13 hydrocarbon chain, a saturated C2-C42 hydrocarbon chain, a saturated C2-C11 hydrocarbon chain, a saturated C2-C10 hydrocarbon chain, a saturated C2-C9 hydrocarbon chain, a saturated C2-C8 hydrocarbon chain, a saturated C2-C7 hydrocarbon chain, a saturated C2-C6hydrocarbon chain, a saturated C2-C5 hydrocarbon chain, a saturated C2-C6hydrocarbon chain, or a saturated C2-C3 hydrocarbon chain, wherein the hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted with one or more RL.

[0066] In some embodiments, R1' is a saturated C3-C20 hydrocarbon chain, a saturated C4-C20 hydrocarbon chain, a saturated C5-C20 hydrocarbon chain, a saturated C6-C20 hydrocarbon chain, a saturated C7-C20 hydrocarbon chain, a saturated C8-C20 hydrocarbon chain, a saturated C9-C20 hydrocarbon chain, a saturated C10-C20 hydrocarbon chain, a saturated C11-C20 hydrocarbon chain, a saturated C12-C20 hydrocarbon chain, a saturated C13-C20 hydrocarbon chain, a saturated CJ4-C20 hydrocarbon chain, a saturated C15-C20 hydrocarbon chain, a saturated C16-C20hydrocarbon chain, a saturated C17-C20 hydrocarbon chain, a saturated C18-C20 hydrocarbon chain, or a saturated C19-C20 hydrocarbon chain, wherein the hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more RL".

[0067] In some embodiments, R1' is a saturated C3-C19 hydrocarbon chain, a saturated C4-C1S hydrocarbon chain, a saturated C5-C17 hydrocarbon chain, a saturated Cs-Cis hydrocarbon chain, a saturated C7-C15 hydrocarbon chain, a saturated CS-CM hydrocarbon chain, a saturated C9-C13 hydrocarbon chain, or a saturated C10-C12 hydrocarbon chain, wherein the hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more RL.

[0068] In some embodiments, RLis a saturated C50-C99 hydrocarbon chain, a saturated C50-C98

[0069] In some embodiments, RLis a saturated Csi-Cioo hydrocarbon chain, a saturated C52-C100p y y

[0070] In some embodiments, RLis a saturated C51-C99 hydrocarbon chain, a saturated C52-C98

[0071] In some embodiments, RLis a saturated C2 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rl. In some embodiments, Rris a saturated Cs hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis a saturated C4 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated Cs hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated Cs hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis a saturated C? hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R!' is a saturated Cs hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R!is a saturated Cy hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1-’. In some embodiments, RLis a saturated C10 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a saturated Cu hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, Rbis a saturated Cn hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:. In some embodiments, RLis a saturated C13 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a saturated C14 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated Cis hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis a saturated Ci6 hydrocarbon chain substituted with at least one saccharide moiety and optionally substitutedwith one or more RL. In some embodiments, RLis a saturated C17 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated Cis hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C19 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, R1is a saturated C20 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C21 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R; . In some embodiments, RLis a saturated C22 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R;In some embodiments, R!is a saturated C23 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C24 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C25 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!. In some embodiments, R:is a saturated C26 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis a saturated C27 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rf. In some embodiments, R1is a saturated C2S hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rr’. In some embodiments, RLis a saturated C29 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rf. In some embodiments, RLis a saturated C30 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R1is a saturated Cn hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1' is a saturated C32 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C33 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, R1is a saturated C34 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, R1' is a saturated C35 hydrocarbon chain substitutedwith at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis a saturated C36 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis a saturated C37 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:' . In some embodiments, R:is a saturated Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C39 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated C40 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rv. In some embodiments, RLis a saturated C41 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL'. In some embodiments, RLis a saturated C42 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C43 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis a saturated C44 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis a saturated C45 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RJ . In some embodiments, RLis a saturated C46 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis a saturated C47 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, R1is a saturated C48 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C49 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, R" is a saturated C50 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C51 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R" . In some embodiments, RLis a saturated C52 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated C53 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In someembodiments, RLis a saturated C54 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL’. In some embodiments, RLis a saturated Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1' is a saturated Cse hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C57 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL\ In some embodiments, RLis a saturated C?8 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, R:is a saturated C59 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated Cc,o hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Ru’. In some embodiments, RLis a saturated Cei hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:' . In some embodiments, RLis a saturated Ce2 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated Cru hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, R1is a saturated C64 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, R!is a saturated Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C06 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, R1is a saturated C.67 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis a saturated Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated CSP hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C70 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1\ In some embodiments, RLis a saturated C71 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, R1is a saturated C72 hydrocarbon chain substituted with at least one saccharidemoiety and optionally substituted with one or more R1' . In some embodiments, RLis a saturated C73 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated C74 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis a saturated C75 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R1is a saturated C?6 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1,is a saturated C77 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C78 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, R1is a saturated C79 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, R1is a saturated Cso hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated Cai hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!In some embodiments, R1,is a saturated Cg2 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a saturated Css hydrocarbon chain substituted with at. least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated Co hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL’. In some embodiments, RLis a saturated Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:' . In some embodiments, R:is a saturated Cse hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis a saturated Cs? hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL"In some embodiments, RLis a saturated Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:' . In some embodiments, RLis a saturated Cs9 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C90 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RijIn some embodiments, RLis a saturatedCei hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1’. In some embodiments, RLis a saturated C92 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated C93 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C94 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C95 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated C96 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis a saturated C97 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R{. In some embodiments, RLis a saturated C99 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis a saturated C100 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL.

[0072] In some embodiments, RLis a linear unsaturated hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1.

[0073] In some embodiments, Rijis a branched unsaturated hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL.

[0074] In some embodiments, RLis an unsaturated C2-C19 hydrocarbon chain, an unsaturated C2-C18 hydrocarbon chain, an unsaturated C2-C17 hydrocarbon chain, an unsaturated C2-C16 hydrocarbon chain, an unsaturated C2-C15 hydrocarbon chain, an unsaturated C2-C14 hydrocarbon chain, an unsaturated C2-C13 hydrocarbon chain, an unsaturated C2-C12 hydrocarbon chain, an unsaturated C2-C11 hydrocarbon chain, an unsaturated C2-C10 hydrocarbon chain, an unsaturated C2-C9 hydrocarbon chain, an unsaturated C2-C8 hydrocarbon chain, an unsaturated C2-C7 hydrocarbon chain, an unsaturated C2-C6hydrocarbon chain, an unsaturated C2-C5 hydrocarbon chain, an unsaturated C2-C6hydrocarbon chain, or an unsaturated C2-C3 hydrocarbon chain, wherein the hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted with one or more R1'

[0075] In some embodiments, RLis an unsaturated C3-C20 hydrocarbon chain, an unsaturated

[0076] In some embodiments, RLis an unsaturated C3-C19 hydrocarbon chain, an unsaturated C4-C18 hydrocarbon chain, an unsaturated C5-C17 hydrocarbon chain, an unsaturated Ce-Cie hydrocarbon chain, an unsaturated C7-C15 hydrocarbon chain, an unsaturated Cs-Ci4 hydrocarbon chain, an unsaturated C9-C13 hydrocarbon chain, or an unsaturated Cio-Cn hydrocarbon chain, wherein the hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more RJ.

[0077] In some embodiments, RLis an unsaturated C50-C99 hydrocarbon chain, an unsaturated

[0078] In some embodiments, R1' is an unsaturated C51-C100 hydrocarbon chain, an unsaturated

[0079] In some embodiments, R:is an unsaturated C51-C99 hydrocarbon chain, an unsaturatedy p y

[0080] In some embodiments, RLis an unsaturated C2 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R5In some embodiments, RLis an unsaturated C3 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated C4 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL'. In some embodiments, RLis an unsaturated C5 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RE. In some embodiments, RLis an unsaturated C~6 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments,RLis an unsaturated C? hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rij. In some embodiments, RLis an unsaturated Cs hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RJ. In some embodiments, R1is an unsaturated C9 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C10 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:In some embodiments, R!jis an unsaturated C11 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:. In some embodiments, RLis an unsaturated Ci 2 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, R1is an unsaturated C13 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated CM hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated Cis hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R' . In some embodiments, R1' is an unsaturated Ci 6 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C17 hydrocarbon chain substituted with at. least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated Cis hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL’. In some embodiments, RLis an unsaturated C19 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rr’ In some embodiments, RLis an unsaturated C20 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated Csi hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C22 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more. In some embodiments, RLis an unsaturated C23 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C24 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted withone or more RL. In some embodiments, RLis an unsaturated C25 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C26 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is an unsaturated C27 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R' . In some embodiments, RLis an unsaturated C?,8 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated C29 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C30 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C31 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis an unsaturated C32 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C33 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis an unsaturated C34 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RJ . In some embodiments, R:is an unsaturated C35 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C36 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis an unsaturated C37 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL, In some embodiments, iV is an unsaturated C38 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C39 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis an unsaturated C40 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C41 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, R1is an unsaturated Cu?. hydrocarbon chain substituted with at least onesaccharide moiety and optionally substituted with one or more R?' . In some embodiments, RLis an unsaturated C43 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rv. In some embodiments, RLis an unsaturated C44 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C45 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C4.5 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!. In some embodiments, R1is an unsaturated C47 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated C48 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C49 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R{. In some embodiments, RLis an unsaturated Cso hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R1is an unsaturated Csi hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!. In some embodiments, RLis an unsaturated C52 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis an unsaturated C53 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C54 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is an unsaturated C55 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!In some embodiments, RLis an unsaturated C56 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C57 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, R1is an unsaturated C59 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' In some embodiments, RLis an unsaturated Csohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated Cei hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated Ces hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:' . In some embodiments, Rris an unsaturated C53 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!j. In some embodiments, RLis an unsaturated Csr hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated Ces hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C66 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL’ In some embodiments, RLis an unsaturated C&7 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is an unsaturated C69 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C70 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C71 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C72 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C73 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis an unsaturated C74 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C75 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated C76 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated C77 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In someembodiments, RLis an unsaturated Os hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL’. In some embodiments, RLis an unsaturated C79 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R1is an unsaturated Cso hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated Csz hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, Rbis an unsaturated Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!In some embodiments, RLis an unsaturated Cs4 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is an unsaturated Cs? hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated Cs6 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R‘ In some embodiments, RLis an unsaturated C87 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis an unsaturated Css hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is an unsaturated CSQ hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, R1is an unsaturated C<w hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, RLis an unsaturated Cm hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated C92 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C93 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated C94 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, Rbis an unsaturated C95 hydrocarbon chain substituted with at least one saccharide moiety andoptionally substituted with one or more RLIn some embodiments, RLis an unsaturated C96 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated C97 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more 1V . In some embodiments, RLis an unsaturated C98 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R!Jis an unsaturated C99 hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more IV . In some embodiments, R1is an unsaturated Cioo hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' .

[0081] In some embodiments, R; is a hydrocarbon chain hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL.

[0082] In some embodiments, IV is a saturated hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb .

[0083] In some embodiments, RLis an unsaturated hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' .

[0084] In some embodiments, IV' is a linear hetero-hydrocarbon substituted with at least one saccharide moiety and optionally substituted with one or more R" .

[0085] In some embodiments, RLis a branched hetero-hydrocarbon substituted with at least one saccharide moiety and optionally substituted with one or more R1-'.

[0086] In some embodiments, RLis a 2- to 19-membered hetero-hydrocarbon chain, a 2- to 18- membered hetero-hydrocarbon chain, a 2- to 17-membered hetero-hydrocarbon chain, a 2- to 16- membered hetero-hydrocarbon chain, a 2- to 15-membered hetero-hydrocarbon chain, a 2- to 14- membered hetero-hydrocarbon chain, a 2- to 13-membered hetero-hydrocarbon chain, a 2- to 12- membered hetero-hydrocarbon chain, a 2- to 11 -membered hetero-hydrocarbon chain, a 2- to 10- membered hetero-hydrocarbon chain, a 2- to 9-membered hetero-hydrocarbon chain, a 2- to 8- niembered hetero-hydrocarbon chain, a 2- to 7-membered hetero-hydrocarbon chain, a 2- to 6- membered hetero-hydrocarbon chain, a 2- to 5-membered hetero-hydrocarbon chain, a 2- to 4- memberecl hetero-hydrocarbon chain, or a 2- to 3-membered hetero-hydrocarbon chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted with one or more IV'

[0087] In some embodiments, RLis a 3- to 20-membered hetero-hydrocarbon chain, a 4- to 20- membered hetero-hydrocarbon chain, a 5- to 20-membered hetero-hydrocarbon chain, a 6- to 20- membered hetero-hydrocarbon chain, a 7- to 20-membered hetero-hydrocarbon chain, a 8- to 20- membered hetero-hydrocarbon chain, a 9- to 20-membered hetero-hydrocarbon chain, a 10- to 20-membered hetero-hydrocarbon chain, a 11- to 20-membered hetero-hydrocarbon chain, a 12- to 20-membered hetero-hydrocarbon chain, a 13- to 20-membered hetero-hydrocarbon chain, a 14- to 20-membered hetero-hydrocarbon chain, a 15- to 20-membered hetero-hydrocarbon chain, a 16- to 20-membered hetero-hydrocarbon chain, a 17- to 20-membered hetero-hydrocarbon chain, a 18- to 20-membered hetero-hydrocarbon chain, or a 19- to 20-membered heterohydrocarbon chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more iV .

[0088] In some embodiments, REis a 3- to 19-membered hetero-hydrocarbon chain, a 4- to 18- membered hetero-hydrocarbon chain, a 5- to 17-membered hetero-hydrocarbon chain, a 6- to 16- membered hetero-hydrocarbon chain, a 7- to 15-membered hetero-hydrocarbon chain, a 8- to 14- membered hetero-hydrocarbon chain, a 9- to 13-membered hetero-hydrocarbon chain, or a 10- to12-membered hetero-hydrocarbon chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more RL

[0089] In some embodiments, R:is a 50- to 99-membered hetero-hydrocarbon chain, a 50- to 98-membered hetero-hydrocarbon chain, a 50- to 97-membered hetero-hydrocarbon chain, a 50- to 96-membered hetero-hydrocarbon chain, a 50- to 95-membered hetero-hydrocarbon chain, a 50- to 94-membered hetero-hydrocarbon chain, a 50- to 93-membered hetero-hydrocarbon chain, a 50- to 92-membered hetero-hydrocarbon chain, a 50- to 91-membered hetero-hydrocarbon chain, a 50- to 90-membered hetero-hydrocarbon chain, a 50- to 89-membered heterohydrocarbon chain, a 50- to 88-membered hetero-hydrocarbon chain, a 50- to 87-membered hetero-hydrocarbon chain, a 50- to 86-membered hetero-hydrocarbon chain, a 50- to 85- membered hetero-hydrocarbon chain, a 50- to 84-membered hetero-hydrocarbon chain, a 50- to 83-membered hetero-hydrocarbon chain, a 50- to 82-membered hetero-hydrocarbon chain, a 50- to 81 -membered hetero-hydrocarbon chain, a 50- to 80-membered hetero-hydrocarbon chain, a 50- to 79-membered hetero-hydrocarbon chain, a 50- to 78-membered hetero-hydrocarbon chain, a 50- to 77-membered hetero-hydrocarbon chain, a 50- to 76-membered hetero-hydrocarbon chain, a 50- to 75-membered hetero-hydrocarbon chain, a 50- to 74-membered hetero-hydrocarbon chain, a 50- to 73-membered hetero-hydrocarbon chain, a 50- to 72-membered hetero-hydrocarbon chain, a 50- to 71 -membered hetero-hydrocarbon chain, a 50- to 70- membered hetero-hydrocarbon chain, a 50- to 69-membered hetero-hydrocarbon chain, a 50- to 68-membered hetero-hydrocarbon chain, a 50- to 67-membered hetero-hydrocarbon chain, a 50- io 66-membered hetero-hydrocarbon chain, a 50- to 65-membered hetero-hydrocarbon chain, a 50- to 64-membered hetero-hydrocarbon chain, a 50- to 63-membered hetero-hydrocarbon chain, a 50- to 62-membered hetero-hydrocarbon chain, a 50- to 61 -membered hetero-hydrocarbon chain, a 50- to 60-membered hetero-hydrocarbon chain, a 50- to 59-membered heterohydrocarbon chain, a 50- to 58-membered hetero-hydrocarbon chain, a 50- to 57-membered hetero-hydrocarbon chain, a 50- to 56-membered hetero-hydrocarbon chain, a 50- to 55- membered hetero-hydrocarbon chain, a 50- to 54-membered hetero-hydrocarbon chain, a 50- to53-membered hetero-hydrocarbon chain, a 50- to 52-membered hetero-hydrocarbon chain, or a 50- to 51 -membered hetero-hydrocarbon chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted with one or more R1' .

[0090] In some embodiments, RLis a 51- to 100-membered hetero-hydrocarbon chain, a 52- to 100-membered hetero-hydrocarbon chain, a 53- to 100-membered hetero-hydrocarbon chain, a54- to 100-membered hetero-hydrocarbon chain, a 55- to 100-membered hetero-hydrocarbon chain, a 56- to 100-membered hetero-hydrocarbon chain, a 57- to 100-membered heterohydrocarbon chain, a 58- to 100-membered hetero-hydrocarbon chain, a 59- to 100-membered hetero-hydrocarbon chain, a 60- to 100-membered hetero-hydrocarbon chain, a 61- to 100- membered hetero-hydrocarbon chain, a 62- to 100-membered hetero-hydrocarbon chain, a 63- to 100-membered hetero-hydrocarbon chain, a 64- to 100-membered hetero-hydrocarbon chain, a 65- to 100-membered hetero-hydrocarbon chain, a 66- to 100-membered hetero-hydrocarbon chain, a 67- to 100-membered hetero-hydrocarbon chain, a 68- to 100-membered heterohydrocarbon chain, a 69- to 100-membered hetero-hydrocarbon chain, a 70- to 100-membered hetero-hydrocarbon chain, a 71- to 100-membered hetero-hydrocarbon chain, a 72- to 100- membered hetero-hydrocarbon chain, a 73- to 100-membered hetero-hydrocarbon chain, a 74- to 100-membered hetero-hydrocarbon chain, a 75- to 100-membered hetero-hydrocarbon chain, a 76- to 100-membered hetero-hydrocarbon chain, a 77- to 100-membered hetero-hydrocarbon chain, a 78- to 100-membered hetero-hydrocarbon chain, a 79- to 100-membered hetero-hydrocarbon chain, a 80- to 100-membered hetero-hydrocarbon chain, a 81 - to 100-membered hetero-hydrocarbon chain, a 82- to 100-membered hetero-hydrocarbon chain, a 83- to 100- membered hetero-hydrocarbon chain, a 84- to 100-membered hetero-hydrocarbon chain, a 85- to 100-membered hetero-hydrocarbon chain, a 86- to 100-membered hetero-hydrocarbon chain, a 87- to 100-membered hetero-hydrocarbon chain, a 88- to 100-membered hetero-hydrocarbon chain, a 89- to 100-membered hetero-hydrocarbon chain, a 90- to 100-membered heterohydrocarbon chain, a 91- to 100-membered hetero-hydrocarbon chain, a 92- to 100-membered hetero-hydrocarbon chain, a 93- to 100-membered hetero-hydrocarbon chain, a 94- to 100- membered hetero-hydrocarbon chain, a 95- to 100-membered hetero-hydrocarbon chain, a 96- to 100-membered hetero-hydrocarbon chain, a 97- to 100-membered hetero- hydrocarb on chain, a 98- to 100-membered hetero-hydrocarbon chain, or a 99- to 100-membered hetero-hydrocarbon chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more RL.

[0091] In some embodiments, RLis a 51- to 99-membered hetero-hydrocarbon chain, a 52- to 98-membered hetero-hydrocarbon chain, a 53- to 97-membered hetero-hydrocarbon chain, a 54- to 96-membered hetero-hydrocarbon chain, a 55- to 95-membered hetero-hydrocarbon chain, a 56- to 94-membered hetero-hydrocarbon chain, a 57- to 93-membered hetero-hydrocarbon chain, a 58- to 92-membered hetero-hydrocarbon chain, a 59- to 91-membered hetero-hydrocarbon chain, a 60- to 90-membered hetero-hydrocarbon chain, a 61- to 89-membered heterohydrocarbon chain, a 62- to 88-membered hetero-hydrocarbon chain, a 63- to 87-membered hetero-hydrocarbon chain, a 64- to 86-membered hetero-hydrocarbon chain, a 65- to 85- membered hetero-hydrocarbon chain, a 66- to 84-membered hetero-hydrocarbon chain, a 67- to 83-membered hetero-hydrocarbon chain, a 68- to 82-membered hetero-hydrocarbon chain, a 69- to 81 -membered hetero-hydrocarbon chain, a 70- to 80-membered hetero-hydrocarbon chain, a 71- to 79-membered hetero-hydrocarbon chain, a 72- to 78-membered hetero-hydrocarbon chain, a 73- to 77-membered hetero-hydrocarbon chain, or a 74- to 76-membered hetero- hydrocarb on chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted with one or more RL.

[0092] In some embodiments, RLis a 2-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a 3-membered hetero-hydrocarbon chain substituted with at least onesaccharide moiety and optionally substituted with one or more R?' . In some embodiments, RLis a 4-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RE. In some embodiments, RLis a 5-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 6-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis a 7-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, Rris a 8-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 9-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 10-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 11 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rf. In some embodiments, R1is a 12-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a 13-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis a 14-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 15-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 16-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!. In some embodiments, RLis a 17-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, R1is a 18-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 19-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 20-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted withone or more Rb. In some embodiments, RLis a 21 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1’. In some embodiments, RLis a 22-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, RLis a 23-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, R1is a 24-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 25-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, Rfis a 26-membered hetero- hydrocarb on chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis a 27-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis a 28-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, RLis a 29-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, RLis a 30-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, RLis a 31 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1-'. In some embodiments, RLis a 32-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, Rris a 33-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, RLis a 34-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, RLis a 35-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, RLis a 36-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis a 37-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RbIn some embodiments,RLis a 38-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL"In some embodiments, RLis a 39-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 40-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 41 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1’ In some embodiments, R1is a 42-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 43-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL>. In some embodiments, RLis a 44-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R1is a 45-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, Rfis a 46-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R‘ In some embodiments, RLis a 47-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 48-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis a 49-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis a 50-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, Rfis a 51 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1’. In some embodiments, R!is a 52-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a 53-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R1is a 54-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 55-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 56-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a 57-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, R1is a 58-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a 59-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 60-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, R1is a 61 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL’ In some embodiments, RLis a 62-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a 63-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1’. In some embodiments, R1' is a 64-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a 65-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a 66-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RrIn some embodiments, RLis a 67-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis a 68-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a 69-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a 70-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 71-membered hetero-hydrocarbon chain substituted with at. least, one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a 72-membered hetero-hydrocarbon chain substituted with at leastone saccharide moiety and optionally substituted with one or more RLin some embodiments, Rijis a 73-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a 74-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL", In some embodiments, RLis a 75-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 76-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R: . In some embodiments, RLis a 77-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1’. In some embodiments, R!is a 78-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL"In some embodiments, RLis a 79-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL", In some embodiments, RLis a 80-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a 81 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 82-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 83-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a 84-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 85-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 86-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis a 87-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R is a 88-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL"In some embodiments, RLis a 89-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionallysubstituted with one or more RL. tn some embodiments, RLis a 90-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a 91 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rij. In some embodiments, RLis a 92-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis a 93-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!In some embodiments, RLis a 94-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis a 95-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 96-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a 97-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RJIn some embodiments, RLis a 98-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLin some embodiments, RLis a 99-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1’. In some embodiments, R1' is a 100-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL".

[0093] In some embodiments, RLis a linear saturated hetero-hydrocarbon substituted with at least one saccharide moiety and optionally substituted with one or more RL.

[0094] In some embodiments, R!is a branched saturated hetero-hydrocarbon substituted with at least one saccharide moiety and optionally substituted with one or more RL.

[0095] In some embodiments, IV' is a saturated 2- to 19-membered hetero-hydrocarbon chain, a saturated 2- to 18-membered hetero-hydrocarbon chain, a saturated 2- to 17-membered heterohydrocarbon chain, a saturated 2- to 16-membered hetero-hydrocarbon chain, a saturated 2- to 15-membered hetero-hydrocarbon chain, a saturated 2- to 14-membered hetero-hydrocarbon chain, a saturated 2- to 13-membered hetero-hydrocarbon chain, a saturated 2- to 12-membered hetero-hydrocarbon chain, a saturated 2- to 1 1 -membered hetero-hydrocarbon chain, a saturated2- to 10-membered hetero-hydrocarbon chain, a saturated 2- to 9-membered hetero-hydrocarbon chain, a saturated 2- to 8-membered hetero-hydrocarbon chain, a saturated 2- to 7-membered hetero-hydrocarbon chain, a saturated 2- to 6-membered hetero-hydrocarbon chain, a saturated 2- to 5-membered hetero-hydrocarbon chain, a saturated 2- to 4-membered hetero-hydrocarbon chain, or a saturated 2- to 3-membered hetero-hydrocarbon chain, wherein the-membered heterohydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted with one or more Rr.

[0096] In some embodiments, IV' is a saturated 3- to 20-membered hetero-hydrocarbon chain, a saturated 4- to 20-membered hetero-hydrocarbon chain, a saturated 5- to 20-membered heterohydrocarbon chain, a saturated 6- to 20-membered hetero-hydrocarbon chain, a saturated 7- to 20-membered hetero-hydrocarbon chain, a saturated 8- to 20-membered hetero-hydrocarbon chain, a saturated 9- to 20-membered hetero-hydrocarbon chain, a saturated 10- to 20-membered hetero-hydrocarbon chain, a saturated 11- to 20-membered hetero-hydrocarbon chain, a saturated 12- to 20-membered hetero-hydrocarbon chain, a saturated 13- to 20-membered heterohydrocarbon chain, a saturated 14- to 20-membered hetero-hydrocarbon chain, a saturated 15- to 20-membered hetero-hydrocarbon chain, a saturated 16- to 20-membered hetero-hydrocarbon chain, a saturated 17- to 20-membered hetero-hydrocarbon chain, a saturated 18- to 20- membered hetero-hydrocarbon chain, or a saturated 19- to 20-membered hetero-hydrocarbon chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more RL.

[0097] In some embodiments, RLis a saturated 3- to 19-membered hetero-hydrocarbon chain, a saturated 4- to 18-membered hetero-hydrocarbon chain, a saturated 5- to 17-membered heterohydrocarbon chain, a saturated 6- to 16-membered hetero-hydrocarbon chain, a saturated 7- to 15-membered hetero-hydrocarbon chain, a saturated 8- to 14-membered hetero-hydrocarbon chain, a saturated 9- to 13 -membered hetero-hydrocarbon chain, or a saturated 10- to 12- membered hetero-hydrocarbon chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more RL.

[0098] In some embodiments, RLis a saturated 50- to 99-membered hetero-hydrocarbon chain, a saturated 50- to 98-membered hetero-hydrocarbon chain, a saturated 50- to 97-membered hetero-hydrocarbon chain, a saturated 50- to 96-membered hetero-hydrocarbon chain, a saturated 50- to 95-membered hetero-hydrocarbon chain, a saturated 50- to 94-membered hetero-hydrocarbon chain, a saturated 50- to 93-membered hetero-hydrocarbon chain, a saturated 50- to 92-membered hetero-hydrocarbon chain, a saturated 50- to 91 -membered hetero-hydrocarbon chain, a saturated 50- to 90-membered hetero-hydrocarbon chain, a saturated 50- to 89- membered hetero-hydrocarbon chain, a saturated 50- to 88-membered hetero-hydrocarbon chain, a saturated 50- to 87-membered hetero-hydrocarbon chain, a saturated 50- to 86-membered hetero-hydrocarbon chain, a saturated 50- to 85-membered hetero-hydrocarbon chain, a saturated 50- to 84-membered hetero-hydrocarbon chain, a saturated 50- to 83-membered heterohydrocarbon chain, a saturated 50- to 82-membered hetero-hydrocarbon chain, a saturated 50- to 81 -membered hetero-hydrocarbon chain, a saturated 50- to 80-membered hetero-hydrocarbon chain, a saturated 50- to 79-membered hetero-hydrocarbon chain, a saturated 50- to 78- membered hetero-hydrocarbon chain, a saturated 50- to 77-membered hetero-hydrocarbon chain, a saturated 50- to 76-membered hetero-hydrocarbon chain, a saturated 50- to 75-membered hetero-hydrocarbon chain, a saturated 50- to 74-membered hetero-hydrocarbon chain, a saturated 50- to 73-membered hetero-hydrocarbon chain, a saturated 50- to 72-membered heterohydrocarbon chain, a saturated 50- to 71 -membered hetero-hydrocarbon chain, a saturated 50- to 70-membered hetero-hydrocarbon chain, a saturated 50- to 69-membered hetero-hydrocarbon chain, a saturated 50- to 68-membered hetero-hydrocarbon chain, a saturated 50- to 67- membered hetero-hydrocarbon chain, a saturated 50- to 66-membered hetero-hydrocarbon chain, a saturated 50- to 65-membered hetero-hydrocarbon chain, a saturated 50- to 64-membered hetero-hydrocarbon chain, a saturated 50- to 63-membered hetero-hydrocarbon chain, a saturated 50- to 62-membered hetero-hydrocarbon chain, a saturated 50- to 61 -membered heterohydrocarbon chain, a saturated 50- to 60-membered hetero-hydrocarbon chain, a saturated 50- to 59-membered hetero-hydrocarbon chain, a saturated 50- to 58-membered hetero-hydrocarbon chain, a saturated 50- to 57-membered hetero-hydrocarbon chain, a saturated 50- to 56- membered hetero-hydrocarbon chain, a saturated 50- to 55-membered hetero-hydrocarbon chain, a saturated 50- to 54-membered hetero-hydrocarbon chain, a saturated 50- to 53-membered hetero-hydrocarbon chain, a saturated 50- to 52-membered hetero-hydrocarbon chain, or a saturated 50- to 51 -membered hetero-hydrocarbon chain, wherein the-membered heterohydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted with one or more RL.

[0099] In some embodiments, RLis a saturated 51 - to 100-membered hetero-hydrocarbon chain, a saturated 52- to 100-membered hetero-hydrocarbon chain, a saturated 53- to 100-membered hetero-hydrocarbon chain, a saturated 54- to 100-membered hetero-hydrocarbon chain, a saturated 55- to 100-membered hetero-hydrocarbon chain, a saturated 56- to 100-membered hetero-hydrocarbon chain, a saturated 57- to 100-membered hetero-hydrocarbon chain, a saturated 58- to 100-membered hetero-hydrocarbon chain, a saturated 59- to 100-membered hetero-hydrocarbon chain, a saturated 60- to 100-membered hetero-hydrocarbon chain, a saturated 61 - to 100-membered hetero-hydrocarbon chain, a saturated 62- to 100-membered hetero-hydrocarbon chain, a saturated 63- to 100-membered hetero-hydrocarbon chain, a saturated 64- to 100-membered hetero-hydrocarbon chain, a saturated 65- to 100-membered hetero-hydrocarbon chain, a saturated 66- to 100-membered hetero-hydrocarbon chain, a saturated 67- to 100-membered hetero-hydrocarbon chain, a saturated 68- to 100-membered hetero-hydrocarbon chain, a saturated 69- to 100-membered hetero-hydrocarbon chain, a saturated 70- to 100-membered hetero-hydrocarbon chain, a saturated 71- to 100-membered hetero-hydrocarbon chain, a saturated 72- to 100-membered hetero-hydrocarbon chain, a saturated 73- to 100-membered hetero-hydrocarbon chain, a saturated 74- to 100-membered hetero-hydrocarbon chain, a saturated 75- to 100-membered hetero-hydrocarbon chain, a saturated 76- to 100-membered hetero-hydrocarbon chain, a saturated 77- to 100-membered hetero-hydrocarbon chain, a saturated 78- to 100-membered hetero-hydrocarbon chain, a saturated 79- to 100-membered hetero-hydrocarbon chain, a saturated 80- to 100-membered hetero-hydrocarbon chain, a saturated 81- to 100-membered hetero-hydrocarbon chain, a saturated 82- to 100-membered hetero-hydrocarbon chain, a saturated 83- to 100-membered hetero-hydrocarbon chain, a saturated 84- to 100-membered hetero-hydrocarbon chain, a saturated 85- to 100-membered hetero-hydrocarbon chain, a saturated 86- to 100-membered hetero-hydrocarbon chain, a saturated 87- to 100-membered hetero-hydrocarbon chain, a saturated 88- to 100-membered hetero-hydrocarbon chain, a saturated 89- to 100-membered hetero-hydrocarbon chain, a saturated 90- to 100-membered hetero-hydrocarbon chain, a saturated 91- to 100-membered hetero-hydrocarbon chain, a saturated 92- to 100-membered hetero-hydrocarbon chain, a saturated 93- to 100-membered hetero-hydrocarbon chain, a saturated 94- to 100-membered hetero-hydrocarbon chain, a saturated 95- to 100-membered hetero-hydrocarbon chain, a saturated 96- to 100-membered hetero-hydrocarbon chain, asaturated 97- to 100-membered hetero-hydrocarbon chain, a saturated 98- to 100-membered hetero-hydrocarbon chain, or a saturated 99- to 100-membered hetero-hydrocarbon chain, wherein the-membered hetero- hydrocarb on chain is substituted with at least one saccharide moiety and is optionally substituted by one or more RL.

[0100] In some embodiments, R:is a saturated 51- to 99-membered hetero-hydrocarbon chain, a saturated 52- to 98-membered hetero-hydrocarbon chain, a saturated 53- to 97-membered hetero-hydrocarbon chain, a saturated 54- to 96-membered hetero-hydrocarbon chain, a saturated 55- to 95-membered hetero-hydrocarbon chain, a saturated 56- to 94-membered heterohydrocarbon chain, a saturated 57- to 93-membered hetero-hydrocarbon chain, a saturated 58- to 92-membered hetero-hydrocarbon chain, a saturated 59- to 91 -membered hetero-hydrocarbon chain, a saturated 60- to 90-membered hetero-hydrocarbon chain, a saturated 61- to 89- membered hetero-hydrocarbon chain, a saturated 62- to 88-membered hetero-hydrocarbon chain, a saturated 63- to 87-membered hetero-hydrocarbon chain, a saturated 64- to 86-membered hetero-hydrocarbon chain, a saturated 65- to 85-membered hetero-hydrocarbon chain, a saturated 66- to 84-membered hetero-hydrocarbon chain, a saturated 67- to 83-membered heterohydrocarbon chain, a saturated 68- to 82-membered hetero-hydrocarbon chain, a saturated 69- to 81 -membered hetero-hydrocarbon chain, a saturated 70- to 80-membered hetero-hydrocarbon chain, a saturated 71- to 79-membered hetero-hydrocarbon chain, a saturated 72- to 78- membered hetero-hydrocarbon chain, a saturated 73- to 77-membered hetero-hydrocarbon chain, or a saturated 74- to 76-membered hetero-hydrocarbon chain, wherein the-membered heterohydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted with one or more RL.

[0101] In some embodiments, RLis a saturated 2-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!. In some embodiments, RLis a saturated 3-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 4-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, Rbis a saturated 5-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated 6-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety andoptionally substituted with one or more RLIn some embodiments, RLis a saturated 7-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 8-membered heterohydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 9-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis a saturated 10-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 1 1-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R!is a saturated 12-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Ru’. In some embodiments, RLis a saturated 13-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated 14- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:. In some embodiments, R1,is a saturated 15- membered hetero-hydrocarbon chain substituted with at. least one saccharide moiety and optionally substituted with one or more Rr. In some embodiments, RLis a saturated 16- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 17- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis a saturated 18- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, R1' is a saturated 19- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R1is a saturated 20- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated 21- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:. In some embodiments, RLis a saturated 22- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety andoptionally substituted with one or more RLIn some embodiments, RLis a saturated 23- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R? . In some embodiments, RLis a saturated 24- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rr’. In some embodiments, RLis a saturated 25- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!j. In some embodiments, RLis a saturated 26- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:. In some embodiments, RLis a saturated 27- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!In some embodiments, RLis a saturated 28- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, R1' is a saturated 29- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 30- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!. In some embodiments, RLis a saturated 31- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a saturated 32- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 33- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rr’ In some embodiments, RLis a saturated 34- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated 35- membered hetero-hydrocarbon chain substituted with at. least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis a saturated 36- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, Rbis a saturated 37- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' In some embodiments, RLis a saturated 38-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rij. In some embodiments, RLis a saturated 39- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R1is a saturated 40- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R‘ . In some embodiments, RLis a saturated 41- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1,. In some embodiments, R1is a saturated 42- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis a saturated 43- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!' . In some embodiments, RLis a saturated 44- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated 45- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R' . In some embodiments, R1' is a saturated 46- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1’. In some embodiments, RLis a saturated 47- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 48- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis a saturated 49- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!In some embodiments, R1' is a saturated 50- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R1is a saturated 51- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated 52- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 53- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety andoptionally substituted with one or more RLIn some embodiments, RLis a saturated 54- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R? . In some embodiments, RLis a saturated 55- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rr’. In some embodiments, RLis a saturated 56- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!j. In some embodiments, RLis a saturated 57- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:. In some embodiments, RLis a saturated 58- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!In some embodiments, RLis a saturated 59- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, R1' is a saturated 60- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 61- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!. In some embodiments, RLis a saturated 62- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a saturated 63- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 64- niembered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rr’ In some embodiments, RLis a saturated 65- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated 66- membered hetero-hydrocarbon chain substituted with at. least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis a saturated 67- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, Rbis a saturated 68- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' In some embodiments, RLis a saturated 69-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rij. In some embodiments, RLis a saturated 70- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R1is a saturated 71- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R‘ . In some embodiments, RLis a saturated 72- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R’ . In some embodiments, R1is a saturated 73- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis a saturated 74- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!' . In some embodiments, RLis a saturated 75- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated 76- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R' . In some embodiments, R1' is a saturated 77- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1’. In some embodiments, RLis a saturated 78- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 79- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis a saturated 80- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!In some embodiments, R1' is a saturated 81- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R1is a saturated 82- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated 83- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:. In some embodiments, RLis a saturated 84- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety andoptionally substituted with one or more RLIn some embodiments, RLis a saturated 85- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R? . In some embodiments, RLis a saturated 86- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rr’. In some embodiments, RLis a saturated 87- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!j. In some embodiments, RLis a saturated 88- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:. In some embodiments, RLis a saturated 89- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!In some embodiments, RLis a saturated 90- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, R1' is a saturated 91- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 92- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R!. In some embodiments, RLis a saturated 93- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a saturated 94- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated 95- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rr’ In some embodiments, RLis a saturated 96- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated 97- membered hetero-hydrocarbon chain substituted with at. least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis a saturated 98- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, Rbis a saturated 99- membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' In some embodiments, RLis a saturated 100-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rij.

[0102] In some embodiments,is a linear unsaturated hetero-hydrocarbon substituted with at least one saccharide moiety and optionally substituted with one or more RL.

[0103] In some embodiments, R:is a branched unsaturated hetero-hydrocarbon substituted with at least one saccharide moiety and optionally substituted with one or more RL".

[0104] In some embodiments, RJ is an unsaturated 2- to 19-membered hetero-hydrocarbon chain, an unsaturated 2- to 18-membered hetero-hydrocarbon chain, an unsaturated 2- to 17- membered hetero-hydrocarbon chain, an unsaturated 2- to 16-membered hetero-hydrocarbon chain, an unsaturated 2- to 15-membered hetero-hydrocarbon chain, an unsaturated 2- to 14- membered hetero-hydrocarbon chain, an unsaturated 2- to 13 -membered hetero-hydrocarbon chain, an unsaturated 2- to 12-membered hetero-hydrocarbon chain, an unsaturated 2- to 11- membered hetero-hydrocarbon chain, an unsaturated 2- to 10-membered hetero-hydrocarbon chain, an unsaturated 2- to 9-membered hetero-hydrocarbon chain, an unsaturated 2- to 8- membered hetero-hydrocarbon chain, an unsaturated 2- to 7-membered hetero-hydrocarbon chain, an unsaturated 2- to 6-membered hetero-hydrocarbon chain, an unsaturated 2- to 5- membered hetero-hydrocarbon chain, an unsaturated 2- to 4-membered hetero-hydrocarbon chain, or an unsaturated 2- to 3 -membered hetero-hydrocarbon chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted with one or more RL.

[0105] In some embodiments, R:' is an unsaturated 3- to 20-membered hetero-hydrocarbon chain, an unsaturated 4- to 20-membered hetero-hydrocarbon chain, an unsaturated 5- to 20- membered hetero-hydrocarbon chain, an unsaturated 6- to 20-membered hetero-hydrocarbon chain, an unsaturated 7- to 20-membered hetero-hydrocarbon chain, an unsaturated 8- to 20- membered hetero-hydrocarbon chain, an unsaturated 9- to 20-membered hetero-hydrocarbon chain, an unsaturated 10- to 20-membered hetero-hydrocarbon chain, an unsaturated 11- to 20- membered hetero-hydrocarbon chain, an unsaturated 12- to 20-membered hetero-hydrocarbon chain, an unsaturated 13- to 20-membered hetero-hydrocarbon chain, an unsaturated 14- to 20- membered hetero-hydrocarbon chain, an unsaturated 15- to 20-membered hetero-hydrocarbon chain, an unsaturated 16- to 20-membered hetero-hydrocarbon chain, an unsaturated 17- to 20- membered hetero-hvdrocarbon chain, an unsaturated 18- to 20-membered hetero-hvdrocarbonchain, or an unsaturated 19- to 20-membered hetero-hydrocarbon chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more RL.

[0106] In some embodiments, R1' is an unsaturated 3- to 19-membered hetero-hydrocarbon chain, an unsaturated 4- to 18-membered hetero-hydrocarbon chain, an unsaturated 5- to 17- membered hetero-hydrocarbon chain, an unsaturated 6- to 16-membered hetero-hydrocarbon chain, an unsaturated 7- to 15-membered hetero-hydrocarbon chain, an unsaturated 8- to 14- membered hetero-hydrocarbon chain, an unsaturated 9- to 13-membered hetero-hydrocarbon chain, or an unsaturated 10- to 12-membered hetero-hydrocarbon chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more R1.

[0107] In some embodiments, REis an unsaturated 50- to 99-membered hetero-hydrocarbon chain, an unsaturated 50- to 98-membered hetero-hydrocarbon chain, an unsaturated 50- to 97- membered hetero-hydrocarbon chain, an unsaturated 50- to 96-membered hetero-hydrocarbon chain, an unsaturated 50- to 95-membered hetero-hydrocarbon chain, an unsaturated 50- to 94- membered hetero-hydrocarbon chain, an unsaturated 50- to 93-membered hetero-hydrocarbon chain, an unsaturated 50- to 92-membered hetero-hydrocarbon chain, an unsaturated 50- to 91- membered hetero-hydrocarbon chain, an unsaturated 50- to 90-membered hetero-hydrocarbon chain, an unsaturated 50- to 89-membered hetero-hydrocarbon chain, an unsaturated 50- to 88- membered hetero-hydrocarbon chain, an unsaturated 50- to 87-membered hetero-hydrocarbon chain, an unsaturated 50- to 86-membered hetero-hydrocarbon chain, an unsaturated 50- to 85- membered hetero-hydrocarbon chain, an unsaturated 50- to 84-membered hetero-hydrocarbon chain, an unsaturated 50- to 83-membered hetero-hydrocarbon chain, an unsaturated 50- to 82- membered hetero-hydrocarbon chain, an unsaturated 50- to 81-membered hetero-hydrocarbon chain, an unsaturated 50- to 80-membered hetero-hydrocarbon chain, an unsaturated 50- to 79- membered hetero-hydrocarbon chain, an unsaturated 50- to 78-membered hetero-hydrocarbon chain, an unsaturated 50- to 77-membered hetero-hydrocarbon chain, an unsaturated 50- to 76- membered hetero-hydrocarbon chain, an unsaturated 50- to 75-membered hetero-hydrocarbon chain, an unsaturated 50- to 74-membered hetero-hydrocarbon chain, an unsaturated 50- to 73- membered hetero-hydrocarbon chain, an unsaturated 50- to 72-membered hetero-hydrocarbon chain, an unsaturated 50- to 71 -membered hetero-hydrocarbon chain, an unsaturated 50- to 70-membered hetero-hydrocarbon chain, an unsaturated 50- to 69-membered hetero-hydrocarbon chain, an unsaturated 50- to 68-membered hetero-hydrocarbon chain, an unsaturated 50- to 67- membered hetero-hydrocarbon chain, an unsaturated 50- to 66-membered hetero-hydrocarbon chain, an unsaturated 50- to 65-membered hetero-hydrocarbon chain, an unsaturated 50- to 64- membered hetero-hydrocarbon chain, an unsaturated 50- to 63-membered hetero-hydrocarbon chain, an unsaturated 50- to 62-membered hetero-hydrocarbon chain, an unsaturated 50- to 61- membered hetero-hydrocarbon chain, an unsaturated 50- to 60-membered hetero-hydrocarbon chain, an unsaturated 50- to 59-membered hetero-hydrocarbon chain, an unsaturated 50- to 58- membered hetero-hydrocarbon chain, an unsaturated 50- to 57-membered hetero-hydrocarbon chain, an unsaturated 50- to 56-membered hetero-hydrocarbon chain, an unsaturated 50- to 55- menibered hetero-hydrocarbon chain, an unsaturated 50- to 54-membered hetero-hydrocarbon chain, an unsaturated 50- to 53-membered hetero-hydrocarbon chain, an unsaturated 50- to 52- membered hetero-hydrocarbon chain, or an unsaturated 50- to 51 -membered hetero-hydrocarbon chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety7and is optionally substituted with one or more R1.

[0108] In some embodiments, R!' is an unsaturated 51- to 100-membered hetero-hydrocarbon chain, an unsaturated 52- to 100-membered hetero-hydrocarbon chain, an unsaturated 53- to 100- membered hetero-hydrocarbon chain, an unsaturated 54- to 100-membered hetero-hydrocarbon chain, an unsaturated 55- to 100-membered hetero-hydrocarbon chain, an unsaturated 56- to 100- membered hetero-hydrocarbon chain, an unsaturated 57- to 100-membered hetero-hydrocarbon chain, an unsaturated 58- to 100-membered hetero-hydrocarbon chain, an unsaturated 59- to 100- membered hetero-hydrocarbon chain, an unsaturated 60- to 100-membered hetero-hydrocarbon chain, an unsaturated 61- to 100-membered hetero-hydrocarbon chain, an unsaturated 62- to 100- membered hetero-hydrocarbon chain, an unsaturated 63- to 100-membered hetero-hydrocarbon chain, an unsaturated 64- to 100-membered hetero-hydrocarbon chain, an unsaturated 65- to 100- membered hetero-hydrocarbon chain, an unsaturated 66- to 100-membered hetero-hydrocarbon chain, an unsaturated 67- to 100-membered hetero-hydrocarbon chain, an unsaturated 68- to 100- membered hetero-hydrocarbon chain, an unsaturated 69- to 100-membered hetero-hydrocarbon chain, an unsaturated 70- to 100-membered hetero-hydrocarbon chain, an unsaturated 71- to 100- membered hetero-hydrocarbon chain, an unsaturated 72- to 100-membered hetero-hydrocarbon chain, an unsaturated 73- to 100-membered hetero-hydrocarbon chain, an unsaturated 74- to 100-membered hetero-hydrocarbon chain, an unsaturated 75- to 100-membered hetero-hydrocarbon chain, an unsaturated 76- to 100-membered hetero-hydrocarbon chain, an unsaturated 77- to 100- membered hetero-hydrocarbon chain, an unsaturated 78- to 100-membered hetero-hydrocarbon chain, an unsaturated 79- to 100-membered hetero-hydrocarbon chain, an unsaturated 80- to 100- membered hetero-hydrocarbon chain, an unsaturated 81- to 100-membered hetero-hydrocarbon chain, an unsaturated 82- to 100-membered hetero-hydrocarbon chain, an unsaturated 83- to 100- membered hetero-hydrocarbon chain, an unsaturated 84- to 100-membered hetero-hydrocarbon chain, an unsaturated 85- to 100-membered hetero-hydrocarbon chain, an unsaturated 86- to 100- membered hetero-hydrocarbon chain, an unsaturated 87- to 100-membered hetero-hydrocarbon chain, an unsaturated 88- to 100-membered hetero-hydrocarbon chain, an unsaturated 89- to 100- membered hetero-hydrocarbon chain, an unsaturated 90- to 100-membered hetero-hydrocarbon chain, an unsaturated 91- to 100-membered hetero-hydrocarbon chain, an unsaturated 92- to 100- membered hetero-hydrocarbon chain, an unsaturated 93- to 100-membered hetero-hydrocarbon chain, an unsaturated 94- to 100-membered hetero-hydrocarbon chain, an unsaturated 95- to 100- membered hetero-hydrocarbon chain, an unsaturated 96- to 100-membered hetero-hydrocarbon chain, an unsaturated 97- to 100-membered hetero-hydrocarbon chain, an unsaturated 98- to 100- membered hetero-hydrocarbon chain, or an unsaturated 99- to 100-membered heterohydrocarbon chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted by one or more R:\

[0109] In some embodiments, Rijis an unsaturated 51- to 99-membered hetero-hydrocarbon chain, an unsaturated 52- to 98-membered hetero-hydrocarbon chain, an unsaturated 53- to 97- membered hetero-hydrocarbon chain, an unsaturated 54- to 96-membered hetero-hydrocarbon chain, an unsaturated 55- to 95-membered hetero-hydrocarbon chain, an unsaturated 56- to 94- membered hetero-hydrocarbon chain, an unsaturated 57- to 93-membered hetero-hydrocarbon chain, an unsaturated 58- to 92-membered hetero-hydrocarbon chain, an unsaturated 59- to 91- membered hetero-hydrocarbon chain, an unsaturated 60- to 90-membered hetero-hydrocarbon chain, an unsaturated 61- to 89-membered hetero-hydrocarbon chain, an unsaturated 62- to 88- membered hetero-hydrocarbon chain, an unsaturated 63- to 87-membered hetero-hydrocarbon chain, an unsaturated 64- to 86-membered hetero-hydrocarbon chain, an unsaturated 65- to 85- membered hetero-hydrocarbon chain, an unsaturated 66- to 84-membered hetero-hydrocarbon chain, an unsaturated 67- to 83 -membered hetero-hydrocarbon chain, an unsaturated 68- to 82-membered hetero-hydrocarbon chain, an unsaturated 69- to 81 -membered hetero-hydrocarbon chain, an unsaturated 70- to 80-membered hetero-hydrocarbon chain, an unsaturated 71- to 79- membered hetero-hydrocarbon chain, an unsaturated 72- to 78-membered hetero-hydrocarbon chain, an unsaturated 73- to 77-membered hetero-hydrocarbon chain, or an unsaturated 74- to 76-membered hetero-hydrocarbon chain, wherein the-membered hetero-hydrocarbon chain is substituted with at least one saccharide moiety and is optionally substituted with one or more RL'.

[0110] In some embodiments, IV' is an unsaturated 2-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R:. In some embodiments, iV' is an unsaturated 3-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL'. In some embodiments, RLis an unsaturated 4-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis an unsaturated 5-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1' is an unsaturated 6-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis an unsaturated 7-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis an unsaturated 8-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is an unsaturated 9-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1' is an unsaturated 10-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 11-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 12-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis an unsaturated 13-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn someembodiments, RLis an unsaturated 14-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 15-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 16-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis an unsaturated 17-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 18-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rl\ In some embodiments, RLis an unsaturated 19-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 20-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated 21 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R is an unsaturated 22-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R!is an unsaturated 23-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 24-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 25-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R5In some embodiments, RLis an unsaturated 26-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 27-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 28-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is an unsaturated 29-membered hetero-hydrocarbon chain substituted with atleast one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis an unsaturated 30-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 31 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated 32-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 33-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 34-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis an unsaturated 35-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis an unsaturated 36-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 37-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 38-membered hetero-hvdrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis an unsaturated 39-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is an unsaturated 40-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, Rbis an unsaturated 41 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 42-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 43-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis an unsaturated 44-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn someembodiments, RLis an unsaturated 45-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 46-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 47-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis an unsaturated 48-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 49-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rl\ In some embodiments, RLis an unsaturated 50-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 51 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated 52-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R is an unsaturated 53-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R!is an unsaturated 54-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 55-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 56-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R5In some embodiments, RLis an unsaturated 57-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 58-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 59-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is an unsaturated 60-membered hetero-hydrocarbon chain substituted with atleast one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis an unsaturated 61 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 62-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated 63-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 64-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 65-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis an unsaturated 66-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis an unsaturated 67-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 68-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 69-membered hetero-hvdrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis an unsaturated 70-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is an unsaturated 71 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, Rbis an unsaturated 72-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 73-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 74-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis an unsaturated 75-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn someembodiments, RLis an unsaturated 76-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 77-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 78-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1. In some embodiments, RLis an unsaturated 79-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 80-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more Rl\ In some embodiments, RLis an unsaturated 81 -membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 82-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated 83-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, R is an unsaturated 84-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R!is an unsaturated 85-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 86-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 87-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R5In some embodiments, RLis an unsaturated 88-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 89-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 90-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is an unsaturated 91 -membered hetero-hydrocarbon chain substituted with atleast one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis an unsaturated 92-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 93-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated 94-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 95-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 96-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis an unsaturated 97-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, RLis an unsaturated 98-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 99-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated 100-membered hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1.[Oi l 1] In some embodiments, Rijis a hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL’.

[0112] In some embodiments, R1' is a hetero-hydrocarbon chain with at least one O, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, Rbis a hetero-hydrocarbon chain with at least one N, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, Rlis a heterohydrocarbon chain with at least one S, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more RL'. In some embodiments, RLis a hetero-hydrocarbon chain with at least one P, wherein the heterohydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more RLIn some embodiments, R1' is a hetero-hydrocarbon chain with at least oneSe, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more Rb.

[0113] In some embodiments,is a hetero-hydrocarbon chain with one O, wherein the heterohydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more R:' . In some embodiments, R:is a hetero-hydrocarbon chain with one N, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, RLis a hetero-hydrocarbon chain with one S, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more Rb. In some embodiments, Rbis a hetero-hydrocarbon chain with one P, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more R!In some embodiments, RLis a hetero-hydrocarbon chain with one Se, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more R ' .

[0114] In some embodiments, RLis a saturated hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more RL.

[0115] In some embodiments, IV is a saturated hetero-hydrocarbon chain with at least one O, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a saturated heterohydrocarbon chain with at least one N, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, R1is a saturated hetero-hydrocarbon chain with at least one S, wherein the heterohydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more IV' In some embodiments, R1is a saturated hetero-hydrocarbon chain with at least one P, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis a saturated hetero-hydrocarbon chain with at least one Se, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more IV’.

[0116] In some embodiments, RLis a saturated hetero-hydrocarbon chain with one O, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated hetero-hydrocarbonchain with one N, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more RL’. In some embodiments, RLis a saturated hetero-hydrocarbon chain with one S, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more Rij. In some embodiments, RLis a saturated hetero-hydrocarbon chain with one P, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis a saturated hetero-hydrocarbon chain with one Se, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more R; .

[0117] In some embodiments, RLis an unsaturated hetero-hydrocarbon chain substituted with at least one saccharide moiety and optionally substituted with one or more R1

[0118] In some embodiments, REis an unsaturated hetero-hydrocarbon chain with at least one O, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more RL". In some embodiments, RLis an unsaturated heterohydrocarbon chain with at least one N, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more R1,. In some embodiments, RLis an unsaturated hetero-hydrocarbon chain with at least one S, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more R1’. In some embodiments, RLis an unsaturated heterohydrocarbon chain with at least one P, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted w'ith one or more RL. In some embodiments, R1is an unsaturated hetero-hydrocarbon chain with at least one Se, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more R1

[0119] In some embodiments, R!is an unsaturated hetero-hydrocarbon chain with one O, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more R1In some embodiments, RLis an unsaturated heterohydrocarbon chain with one N, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more R1' . In some embodiments, RLis an unsaturated hetero-hydrocarbon chain with one S, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or moreRL. In some embodiments, RLis an unsaturated hetero-hydrocarbon chain with one P, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more RL. In some embodiments, RLis an unsaturated heterohydrocarbon chain with one Se, wherein the hetero-hydrocarbon chain is substituted with at least one saccharide moiety and optionally substituted with one or more RL".

[0120] In some embodiments, RLis substituted with one, two, or three saccharide moieties. In some embodiments, RLis substituted with one saccharide moiety. In some embodiments, RLis substituted with two saccharide moieties. In some embodiments, RLis substituted with three saccharide moieties.

[0121] In some embodiments, RLis a hetero-hydrocarbon chain comprising one or more -NH-.

[0122] In some embodiments, R'ris a hetero-hydrocarbon chain comprising one or more -O-.

[0123] In some embodiments, RHs a hetero-hydrocarbon chain optionally substituted with oxo.

[0124] In some embodiments, R’ is a hetero-hydrocarbon chain substituted with oxo.

[0125] In some embodiments, RLis a hetero-hydrocarbon chain comprising one or more -NH- and is optionally substituted with oxo.

[0126] In some embodiments, R'ris a hetero-hydrocarbon chain comprising one or more -NH- and is substituted with oxo.

[0127] In some embodiments, RLis a hetero-hydrocarbon chain substituted with one or more R!’, and the substituted hetero-hydrocarbon chain comprises one or more -C(:;;:O)-NH-.

[0128] In some embodiments, Rijis a hetero-hydrocarbon chain substituted with one or moreR1J’, and the substituted hetero-hydrocarbon chain comprises one or more, wherein denotes attachment to the rest of the hetero-hydrocarbon chain.

[0129] In some embodiments, RHs a hetero-hydrocarbon chain substituted with one or more R1’, and the substituted hetero-hydrocarbon chain comprises one or more phenylene.

[0130] In some embodiments, at least one internal position of the hetero-hydrocarbon chain is substituted with a saccharide moiety In some embodiments, at least one terminal position of the hetero-hydrocarbon chain is substituted with a saccharide moiety.

[0131] In some embodiments, at least one internal position of RLis substituted with a saccharide moiety.

[0132] In some embodiments, at least one terminal position of Rf' is substituted with a saccharide moiety.

[0133] In some embodiments, L is of Formula (A),wherein:indicates the point of attachment to the rest of the Saccharide-Based Ligand Agent, Saccharide-Based Ligand Scaffold, Saccharide-Based Ligand Unit, or conjugate.

[0134] In some embodiments, of L indicates the point of attachment to the rest of theSaccharide-Based Ligand Agent.

[0135] In some embodiments,of L indicates the point of attachment to the rest of the Saccharide-Based Ligand Scaffold.

[0136] In some embodiments,of L indicates the point of attachment to the rest of the Saccharide-Based Ligand Unit.

[0137] In some embodiments,of L indicates the point of attachment to the rest of the conjugate (e.g., a direct or indirect attachment to one or more Nucleic Acid Agent).

[0138] In some embodiments, E is O.

[0139] In some embodiments, E is S.

[0140] In some embodiments, R" is -ORE1.

[0141] In some embodiments Rris ~N(RE2)2

[0236] In some embodiments, at least one RL1is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, or Br).

[0237] In some embodiments, ml is an integer ranging from 0 to about 90. In some embodiments, ml is an integer ranging from 0 to about 80 In some embodiments, mi ls an integer ranging from 0 to about 70. In some embodiments, ml is an integer ranging from 0 to about 60. In some embodiments, ml is an integer ranging from 0 to about 50. In some embodiments, ml is an integer ranging from 0 to about 40. In some embodiments, ml is an integer ranging from 0 to about 30. In some embodiments, m l is an integer ranging from 0 to about 20. In some embodiments, ml is an integer ranging from 0 to about 10.

[0238] In some embodiments, ml is an integer ranging from about 10 to about 100. In some embodiments, ml is an integer ranging from about 20 to about 100. In some embodiments, ml is an integer ranging from about 30 to about 100. In some embodiments, ml is an integer ranging from about 40 to about 100. In some embodiments, ml is an integer ranging from about 50 to about 100. In some embodiments, m l is an integer ranging from about 60 to about 100. In some embodiments, ml is an integer ranging from about 70 to about 100. In some embodiments, ml is an integer ranging from about 80 to about 100. In some embodiments, ml is an integer ranging from about 90 to about 100.

[0239] In some embodiments, ml is an integer ranging from about 10 to about 90. In some embodiments, ml is an integer ranging from about 20 to about 80 In some embodiments, ml is an integer ranging from about 30 to about 70. In some embodiments, ml is an integer ranging from about 40 to about 60.

[0240] In some embodiments, nil is 0. In some embodiments, ml is about 10. In some embodiments, ml is about 20. In some embodiments, ml is about 30, In some embodiments, m l is about 40. In some embodiments, ml is about 50. In some embodiments, ml is about 60. In some embodiments, ml is about 70. In some embodiments, ml is about 80. In some embodiments, ml is about. 90. In some embodiments, ml is about 100.

[0241] In some embodiments, at least one pl is an integer ranging from 0 to about 90. In some embodiments, at. least one pl is an integer ranging from 0 to about 80. In some embodiments, at least one pl is an integer ranging from 0 to about 70 In some embodiments, at least one pl is an integer ranging from 0 to about 60. In some embodiments, at least one pl is an integer ranging from 0 to about 50. In some embodiments, at least one pl is an integer ranging from 0 to about 40 In some embodiments, at least one pl is an integer ranging from 0 to about 30. In some embodiments, at least one pl is an integer ranging from 0 to about 20. In some embodiments, at least one pl is an integer ranging from 0 to about 10.

[0242] In some embodiments, at least one pl is an integer ranging from about 10 to about 100. In some embodiments, at least one p l is an integer ranging from about 20 to about 100. In some embodiments, at least one pl is an integer ranging from about 30 to about 100. In some embodiments, at least one pl is an integer ranging from about 40 to about 100. In some embodiments, at least one pl is an integer ranging from about 50 to about 100. In some embodiments, at least one pl is an integer ranging from about 60 to about 100. In someembodiments, at least one pl is an integer ranging from about 70 to about 100. In some embodiments, at least one pl is an integer ranging from about 80 to about 100. In some embodiments, at least one pl is an integer ranging from about 90 to about 100.

[0243] In some embodiments, at least one pl is an integer ranging from about 10 to about 90. In some embodiments, at least one pl is an integer ranging from about 20 to about 80. In some embodiments, at least one pl is an integer ranging from about 30 to about 70. In some embodiments, at least one pl is an integer ranging from about 40 to about 60.

[0244] In some embodiments, at least one pl is 0 In some embodiments, at least one pl is about 10. In some embodiments, at least one pl is about 20. In some embodiments, at least one pl is about 30. In some embodiments, at least one pl is about. 40. in some embodiments, at least one pl is about 50. In some embodiments, at least one pl is about 60. In some embodiments, at least one pl is about 70 In some embodiments, at least one pl is about 80. In some embodiments, at least one pl is about 90. In some embodiments, at least one pl is about 100.

[0245] In some embodiments, W is a bond or C(RW)2, i.e.,

[0246] In some embodiments,

[0247] In some embodiments,

[0248] In some embodiments,

[0249] In some embodiments,

[0250] In some embodiments,

[0251] In some embodiments, W is a bond.

[0252] In some embodiments, q is 1

[0253] In some embodiments, q is 2.

[0254] In some embodiments, q is 3.

[0255] In some embodiments, q is 1, and W is a bond or C(Rw)z, i.e.,

[0256] In some embodiments, q is 1, and W is a bond.

[0257] In some embodiments,

[0258] In some embodiments, q

[0261] In some embodiments,

[0262] In some embodiments, at least one Rwis H.

[0263] In some embodiments, each Rwis H.

[0264] In some embodiments, at least one Rwis halogen (e.g., F, Cl, or Br).

[0265] In some embodiments, at least one Rwis C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0266] In some embodiments, at least one Rwis , alkyl (eC.g1.-,C6methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, or Br).

[0267] In some embodiments, at least one Rwis C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, or Br).

[0268] In some embodiments, at least one SA is a saccharide (e.g., monosaccharide, di saccharide, polysaccharide) moiety.

[0269] In some embodiments, at least one SA is a mannose (e.g., monomannose, dimannose, polymannose) moiety .

[0270] In some embodiments, at least one SA is a fucose (e.g., monofucose, difucose, poly fucose) moiety.

[0271] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound of Formula (AA-1),(AA-1) or a pharmaceutically acceptable salt thereof, wherein variables E, R1', L2, W, SA, m2, p2, and q are described herein.

[0272] In some embodiments, L is of Formula (A-l),(A-l) wherein: variables E W SA and q are described herein;

[0273] In some embodiments, at least one L2is -CH2CH2O-, -OCH2CH2-, -C^Oj-NH-, - NH-C(=O)-, or Ci-Cn alkylene optionally substituted with one or more halogen, -OH, -NHz, - NH-C(=O)-(Ci-Ci2 alkyl), or -NH-C(=O)-(Ci-Ci2 haloalkyl).

[0274] In some embodiments, at least one L2is --CH2CH2O--

[0275] In some embodiments, at least one L2is -OCH2CH2-.

[0276] In some embodiments, at least one L2is C( O) \H

[0277] In some embodiments, at least one L2is XI 1 C( ())

[0287] In some embodiments, at least one L2is phenylene or triazoiylene.

[0288] In some embodiments, at least one L2is -O-.

[0289] In some embodiments, at least one L2is -NH-.

[0290] In some embodiments, m2 is an integer ranging from 0 to about 40. In some embodiments, m2 is an integer ranging from 0 to about 30. In some embodiments, m2 is an integer ranging from 0 to about 20. In some embodiments, m2 is an integer ranging from 0 to about 10,

[0291] In some embodiments, m2 is an integer ranging from about 10 to about 50. In some embodiments, m2 is an integer ranging from about 20 to about 50. In some embodiments, m2 is an integer ranging from about 30 to about 50. In some embodiments, m2 is an integer ranging from about 40 to about 50.

[0292] In some embodiments, m2 is an integer ranging from about 10 to about 40 In some embodiments, m2 is an integer ranging from about 20 to about 30.

[0293] In some embodiments, m2 is 0. In some embodiments, m2 is about 10. In some embodiments, m2 is about 20. In some embodiments, m2 is about 30. In some embodiments, m2 is about 40. In some embodiments, m2 is about 50.

[0294] In some embodiments, at least one p2 is an integer ranging from 0 to about 40. In some embodiments, at least one p2 is an integer ranging from 0 to about 30. In some embodiments, at least one p2 is an integer ranging from 0 to about 20. In some embodiments, at least one p2 is an integer ranging from 0 to about 10.

[0295] In some embodiments, at least one p2 is an integer ranging from about. 10 to about 50. In some embodiments, at least one p2 is an integer ranging from about 20 to about 50. In some embodiments, at least one p2 is an integer ranging from about 30 to about 50. In some embodiments, at least one p2 is an integer ranging from about 40 to about 50.

[0296] In some embodiments, at least one p2 is an integer ranging from about 10 to about 40. In some embodiments, at least one p2 is an integer ranging from about 20 to about 30.

[0297] In some embodiments, at least one p2 is 0. In some embodiments, at least one p2 is about 10. In some embodiments, at least one p2 is about 20. In some embodiments, at least one p2 is about 30. In some embodiments, at least one p2 is about 40. In some embodiments, at least one p2 is about 50.

[0298] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound of Formula(AA-i), (AA-ii), (AA-iii), or (AA-iv):or a pharmaceutically acceptable salt thereof, wherein variables E, RELl, R\ ml, pl, and SA are described herein.

[0299] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound of Formula(AA-l-i), (AA-l-ii), (AA-l-iii), or (AA-l -iv):

[0300] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound of Formula(AA-a), (AA-b), (AA-c), (AA-d), (AA-e), or (AA-f):or a pharmaceutically acceptable salt thereof, wherein variables REand SA are described herein.

[0301] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound of Formula (C),or a pharmaceutically acceptable salt thereof, wherein variable L is as described herein.

[0302] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound of Formula(C),or a pharmaceutically acceptable salt thereof, wherein variables E, L1, W, SA, m 1, pl, and q are described herein.

[0303] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound of Formula (C-l),(C-l ) or a pharmaceutically acceptable salt thereof, wherein variables E, L2, W, SA, m2, p2, and q are described herein.

[0304] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound of Formula(C-i), (C-ii), (C-ii i ), or (C-iv):or a pharmaceutically acceptable salt thereof, wherein variables E, L1, R* , ml , pl , and SA are described herein.

[0305] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound of Formula(C-l-i), (C-l-ii), (C-l-iii), or (C-l-iv):or a pharmaceutically acceptable salt thereof, wherein variables E, L2, R\ m2, p2, and SA are described herein

[0306] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound of Formula(C-a), (C-b), (C-c), (C-d), (C-e), or (C-f):or a pharmaceutically acceptable salt thereof, wherein variable SA is described herein

[0307] In some embodiments, L is of Formula (A-i), (A-ii), (A-iii), or (A-iv):-iv), wherein variables E, Ll, Rw, ml, pl, and SA are described herein.

[0308] In some embodiments, L is of Formula (A-l -i), (A-1-ii), (A-l-iii), or (A-l-iv):wherein variables E, L2, R* m2, p2, and SA are described herein.

[0309] In some embodiments, L is of Formula (A-a), (A-b), (A-c), (A-d), (A-e), or (A-f):

[0310] In some embodiments, at least one saccharide moiety is (e.g., each saccharide moiety independently is) of Formula (B):whereinhalogen,independently, II, halogen, Ci-Cb alkyl optionally substituted with one or more halogen, -OH, -SChH, -OSChH, or C1-C6, alkoxy optionally substituted with one or more halogen, wherein* indicates the point of attachment to the rest of Formula (B), and wherein one is present for eachwhereinindicates the point of attachment to the rest of L, and wherein oneis present in Formula (B).[03 I I] In some embodiments, at least one saccharide moiety is (e.g. , each saccharide moiety independently is) of Formula (B-l), (B-2), (B-3), or (B-4):

[0312] In some embodiments, at least one saccharide moiety is (e.g., each saccharide moiety

[0313] In some embodiments, at least one saccharide moiety is (e.g. , each saccharide moiety

[0314] In some embodiments, at least one saccharide moiety is (e.g., each saccharide moiety

[0315] In some embodiments, at least one saccharide moiety is (e.g., each saccharide moiety

[0316] In some embodiments, at least one saccharide moiety is (e.g. , each saccharide moiety independently is) selected from

[0317] In some embodiments, at least one saccharide moiety is (e.g., each saccharide moiety independently is) selected from

[0318] In some embodiments, at least one saccharide moiety is (e.g., each saccharide moiety

[0319] In some embodiments, at least one saccharide moiety is (e.g. , each saccharide moiety independently is) selected from

[0320] In some embodiments, R1’ is H.

[0321] In some embodiments, R1’ is halogen (e.g., F, Cl, or Br).

[0322] In some embodiments, R1’ is Ci-Cs alkyl (e g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0323] In some embodiments, R1’ is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F,Cl, or Br).

[0324] In some embodiments, R1’ is C1-C6 alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, or Br).

[0325] In some embodiments, R1’ is -ORa’.- •

[0326] In some embodiments, R is , wherein indicates the point of attachment tothe rest of L.

[0327] In some embodiments, R1’ is -OH

[0328] In some embodiments, R!’ is -O-(C1-C6alkyl) (e g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).[0.329] In some embodiments, R1’ is -O-(C1-C6alkyl) (e g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, or Br).

[0330] In some embodiments, Rf’ is -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, or Br).

[0331] In some embodiments, R1’ is -OSOJH.

[0332] In some embodiments, R’ ’ is -ORa’, whereini -1- -i-

[0333] In some embodiments, R is * . wherein5indicates the point of attachment to the rest of L.

[0334] In some embodiments, R2’ is H.

[0335] In some embodiments, R2’ is halogen (e.g., F, Cl, or Br).

[0336] In some embodiments, R2’ is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0337] In some embodiments, R2’ is Ci-Ct, alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, or Br)

[0338] In some embodiments, R2’ is , alkCy1l- (C6e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, or Br).

[0339] In some embodiments, R2’ is -ORa’.

[0340] In some embodiments, R2’ is, whereinindicates the point of attachment to the rest of L.

[0341] In some embodiments, R2’ is -OH.

[0342] In some embodiments, R2’ is -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0343] In some embodiments, R2’ is -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, or Br).

[0344] In some embodiments, R2’ is -O-(C1-C6alkyl) (e.g., wherein the C1-C6 alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, or Br).

[0345] In some embodiments, R2’ is -OSOsH.

[0346] In some embodiments, R2’ is -ORa’, wherein

[0347] In some embodiments, R2’ is, whereinindicates the point of attachment to the rest of L.

[0348] In some embodiments, R3’ is H.

[0349] In some embodiments, R3’ is halogen (e.g., F, Cl, or Br).

[0350] In some embodiments, R3’ is C1-C6alkyl (e g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0351] In some embodiments, R3’ is Ci-C-6 alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, or Br).

[0352] In some embodiments, R3’ is C1-C6alkyl (e g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, CI, or Br).

[0353] In some embodiments, R3’ is -OR‘r.— (2) — t— - -1

[0354] In some embodiments, R is5. wherein * indicates the point of attachment to the rest of L.

[0355] In some embodiments, R3’ is -OH

[0356] In some embodiments, R3’ is -O-(Ci-Cf. alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0357] In some embodiments, R3’ is -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, or Br).

[0358] In some embodiments, R3’ is -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, or Br).

[0359] In some embodiments, R3’ is -OSChH.

[0360] In some embodiments, R3’ is -ORa’, wherein

[0361] In some embodiments, R3’ is, whereinindicates the point of attachment to the rest of L.

[0362] In some embodiments, R4’ is H.

[0363] In some embodiments, R4’ is halogen (e.g., F, Cl, or Br).

[0364] In some embodiments, R4’ is C1-C6alkyl (e g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0365] In some embodiments, R4’ is Ci-C-6 alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, or Br).

[0366] In some embodiments, R4’ is C1-C6alkyl (e g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, or Br).

[0367] In some embodiments, R4’ is -OR‘r.— O"'£— -- -I

[0368] In some embodiments, R4’ is « , wherein « indicates the point of attachment to the rest of L.

[0369] In some embodiments, R4’ is -OH

[0370] In some embodiments, R4’ is -O-(Ci-Cf. alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0371] In some embodiments, R4’ is -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, or Br).

[0372] In some embodiments, R4’ is -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, or Br).

[0373] In some embodiments, R4’ is -OSChH.

[0374] In some embodiments, R4’ is -ORa’, wherein

[0375] In some embodiments, R4’ is, whereinindicates the point of attachment to the rest of L.

[0376] In some embodiments, R” is H.

[0377] In some embodiments, R5’ is halogen (e.g., F, Cl, or Br).

[0378] In some embodiments, R3’ is C1-C6alkyl (e g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0379] In some embodiments, R5’ is Ci-C-6 alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, or Br).

[0380] In some embodiments, R5’ is C1-C6alkyl (e g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, or Br).

[0381] In some embodiments, R3’ is -OR‘r.

[0382] In some embodiments, R3' is. whereinindicates the point of attachment to the rest of L.

[0383] In some embodiments, R3’ is -OH

[0384] In some embodiments, R5’ is -O-(Ci-Cf. alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0385] In some embodiments, R5’ is -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, or Br).

[0386] In some embodiments, R3’ is -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, or Br).

[0387] In some embodiments, R3’ is -OSChH.

[0388] In some embodiments, R” is -ORa’, wherein

[0389] In some embodiments, R5' is, whereinindicates the point of attachment to the rest of L.[0.390] In some embodiments, at least one Ra’ is / wherein indicates the point ofattachment to the rest of L.

[0391] In some embodiments, at least one R:i' is H.

[0392] In some embodiments, at least one Ra’ is Cj-Cr, alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0393] In some embodiments, at least one Ra’ is C1-C6alkyl (e g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, or Br).

[0394] In some embodiments, at least one Ra’ is Cj-Ce alkyl (e g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, or Br).

[0395] In some embodiments, at least one Ra’ is -SChH.

[0396] In some embodiments, at least one

[0397] In some embodiments, at least one Rlais, wherein* indicates the point of attachment to the rest of Formula (B).

[0398] In some embodiments, at least one R13is H

[0399] In some embodiments, at least one R! ais halogen (e.g., F, Cl, or Br).

[0400] In some embodiments, at least one Rlais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0401] In some embodiments, at least one Rlais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyi, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0402] In some embodiments, at least one Rlais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g , F, CL Br, or I).

[0403] In some embodiments, at least one Riais -OH.

[0404] In some embodiments, at least one Rlais -SO3H.

[0405] In some embodiments, at least one R1 ais -OSO3H.

[0406] In some embodiments, at least one Riais C1-C6alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy).

[0407] In some embodiments, at least one Rlais C1-C6alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0408] In some embodiments, at least one Rlais C1-C6alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy) substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0409] In some embodiments, at least one Rlais, wherein* indicates the point of attachment to the rest of Formula (B).

[0410] In some embodiments, at least one R2ais H.

[0411] In some embodiments, at least, one R2ais halogen (e.g., F, Cl, or Br).

[0412] In some embodiments, at least one R2ais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0413] In some embodiments, at least one R2ais Ci-Cg alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0414] In some embodiments, at least one R2ais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, CL Br, or I).

[0415] In some embodiments, at least one R2ais -OH

[0416] In some embodiments, at least one R2ais -SOsH.

[0417] In some embodiments, at least one R2ais -OSO3H.

[0418] In some embodiments, at least one R2ais C1-C6alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy).

[0419] In some embodiments, at least one R2ais C1-C6alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy) optionally substituted with one or more halogen (e.g., F, CI, Br, or I).

[0420] In some embodiments, at least one R2ais C1-C6alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy) substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0421] In some embodiments, at least one Rais, wherein * indicates the point otattachment to the rest of Formula (B).

[0422] In some embodiments, at least one R3ais H.

[0423] In some embodiments, at least one RJais halogen (e.g., F, Ci, or Br).

[0424] In some embodiments, at least one R3ais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0425] In some embodiments, at least one R3ais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0426] In some embodiments, at least one R3ais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, CI, Br, or I)

[0427] In some embodiments, at least one R ’ais -OH.

[0428] In some embodiments, at least one R3ais -SO3H.

[0429] In some embodiments, at least one R3ais -OSO3II.

[0430] In some embodiments, at least one R3ais C1-C6alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy).

[0431] In some embodiments, at least one R ’“ is C1-C6alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hex oxy) optionally substituted with one or more halogen (e.g., F, Cl, Br, or 1).

[0432] In some embodiments, at least one R3ais C1-C6alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy) substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0433] In some embodiments, at least one R is5*, wherein2* indicates the point of attachment to the rest of Formula (B).

[0434] In some embodiments, at least one R4ais H.

[0435] In some embodiments, at least one R43is halogen (e.g., F, Ci, or Br).

[0436] In some embodiments, at least one R4ais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0437] In some embodiments, at least one R4ais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0438] In some embodiments, at least one R4ais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0439] In some embodiments, at least one R4ais -OH.

[0440] In some embodiments, at least one R4ais -SChH.

[0441] In some embodiments, at least one R4ais -OSO3H.

[0442] In some embodiments, at least one R4® is C1-C6alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy) .

[0443] In some embodiments, at least one R4ais Ci-Ct, alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0444] In some embodiments, at least one R4ais C1-C6alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy) substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0445] In some embodiments, at least one R5® is, wherein* indicates the point of attachment to the rest of Formula (B).

[0446] In some embodiments, at least one R'3is H

[0447] In some embodiments, at least one R3ais halogen (e.g., F, Cl, or Br).

[0448] In some embodiments, at least one R5® is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyi, t-butyl, pentyl, or hexyl).

[0449] In some embodiments, at least one R5ais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I)

[0450] In some embodiments, at least one R5® is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, Br, or I)

[0451] In some embodiments, at least one R3ais -OH.

[0452] In some embodiments, at least one R5ais -SChH.

[0453] Ln some embodiments, at least one R5ais -OSO3H.

[0454] In some embodiments, at least one R'ais C1-C6alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy).

[0455] In some embodiments, at least one Raais Ci-Co alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0469] In some embodiments, at least one RLis -N(Ci-Ci2 alky1)(Ci-Ci2 haloalkyl) (e.g., -N(Ci, C2, Cs, C4, Cs, Cs, C7, Cs, C9, Cio, CH, or C12 alkyl)(Ci, C2, Cs, C4, Cs, Ce, C7, Cs, C9, Cio, Cii, or C12 haloalkyl)).

[0470] In some embodiments, at least one R1is -N(Ci-Cn haloalkyl); (e.g., -N(Ci, C2, Cs, C4, C5, Cs, C7, Cs, C9, Cio, C11, or C12 haloalkyl);).

[0471] In some embodiments, at least one RLis Cs-Cs cycloalkyl (e.g., C3, C4, Cs, Cs, C7, or Cs cycloalkyl).

[0472] In some embodiments, at least one R1’ is 3- to 8-membered heterocycloalkyl (e.g., 3-, 4-, 5-, 6-, 7-, or 8-membered heterocycloalkyl).

[0473] In some embodiments, at least one R1' is Cs-Cio aryl (e.g., phenyl or naphthyl).

[0474] In some embodiments, at least one RLis 5- to 10-membered heteroaryl (e.g., 5-, 6-, 7-, 8-, 9~, or 10-membered heteroaryl).

[0475] In some embodiments, two R1, together with the one or more intervening atoms, form C3-C8 cycloalkyl (e.g., C3, C4, Cs, Cs, C7, or Cs cycloalkyl).

[0478] In some embodiments, two RL’, together with the one or more intervening atoms, form 3- to 8-membered heterocycloalkyl (e.g, 3-, 4-, 5-, 6-, 7-, or 8-membered heterocycloalkyl).

[0479] In some embodiments, two RL, together with the one or more intervening atoms, form 3- to 8-membered heterocycloalkyl (e g, 3-, 4-, 5-, 6-, 7-, or 8-membered heterocycloalkyl) optionally substituted with one or more oxo, cyano, halogen (e.g, F, Cl, or Br), -OH, -O(Cj-Ci2

[0480] In some embodiments, two RL", together with the one or more intervening atoms, form 3- to 8-membered heterocycloalkyl (e.g., 3-, 4-, 5-, 6-, 7-, or 8-membered heterocycloalkyl)y

[0482] In some embodiments, two RLtogether with the one or more intervening atoms, formheterocycloalkyl), Cs-Cio aryl (e.g., phenyl or naphthyl), or 5- to 10-membered heteroaryl (e g., 5-, 6-, 7-, 8-, 9-, or 10-membered heteroaryl)..

[0483] Ln some embodiments, two R!' , together with the one or more intervening atoms, form

[0484] In some embodiments, two RLtogether with the one or more intervening atoms, form 5- to 10-membered heteroaryl (e.g., 5-, 6-, 7-, 8-, 9-, or 10-membered heteroaryl).

[0485] In some embodiments, two Rij, together with the one or more intervening atoms, form 5-10-membered heteroaryl (e.g., 5-, 6-, 7-, 8-, 9-, or 10-membered heteroaryl)..

[0486] In some embodiments, two R1' , together with the one or more intervening atoms, form 5-

[0487] In some embodiments, two R; together with the one or more intervening atoms, form triazolyl.

[0488] In some embodiments, two R:' , together with the one or more intervening atoms, form 1,2,3 -triazolyl.

[0489] In some embodiments, two RL’, together with the one or more intervening atoms, form, independently indicates the point of attachment to the rest of L.wherein each SA is independently a saccharide moiety, and * indicates the point of attachment to the rest of the Saccharide-Based Ligand Agent, Saccharide-Based Ligand Scaffold, Saccharide-Based Ligand Unit, or conjugate.wherein each SA is independently a saccharide moiety, and ’ indicates the point of attachment to the rest of the Saccharide-Based Ligand Agent, Saccharide-Based Ligand Scaffold, Saccharide-Based Ligand Unit, or conjugate.

[0492] In some embodiments, RLcomprisesj_ -i- wherein2indicates the point of attachment to a saccharide moiety and?indicates the point of attachment to the rest of L.attachment to a saccharide moiety and indicates the point of attachment to the rest of L.

[0494] In some embodiments, L is selected from the structures described in Table X, and stereoisomers thereof, wherein indicates the point of attachment to the rest of theSaccharide-Based Ligand Agent, Saccharide-Based Ligand Scaffold, Saccharide-Based Ligand Unit, or conjugate.0495] In some embodiments, L is selected from the structures described in Table X.

[0496] In some embodiments, L is a stereoisomer of a structure described in Table X

[0497] In some embodiments, L is selected from X-2, X-3, X-4, X-5, X-6, X-l 1, X-13, X- 14, X-I 5, X-l 6, X-l 7, X-l 8, X-l 9, X-20, and X-21.

[0498] In some embodiments, L is X-l . In some embodiments, L is X-2. In some embodiments, L is X-3. In some embodiments, L is X-4. In some embodiments, L is X-5. In some embodiments, L is X-6. In some embodiments, L is X-7. In some embodiments, L is X-8. In some embodiments, L is X-9. In some embodiments, L is X-10. In some embodiments, L is X- I I . In some embodiments, L is X-12. In some embodiments, L is X-13. In some embodiments, L is X-14. In some embodiments, L is X-l 5. In some embodiments, L is X-16. In some embodiments, L is X-17. In some embodiments, L is X-18. In some embodiments, I., is X-19. In some embodiments, L is X-20. In some embodiments, L is X-21.

[0499] In some embodiments, L, is directly or indirectly (e.g., via a Linker Unit) attached to a Nucleic Acid .Agent at the 5’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0500] In some embodiments, L is directly attached to a Nucleic Acid Agent at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0501] In some embodiments, L is indirectly (e.g., via a Linker Unit) attached a Nucleic Acid Agent at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0502] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound is described in Table Y or a compound in Table Y, wherein one or more the moi eties in the compound (e.g., -OH) are protected with a protection group described herein, or a pharmaceutically acceptable salt or stereoisomer thereof.Table Y

[0503] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound is described in Table Y or a compound in Table Y, wherein one or more the moieties in the compound (e.g., -OH) are protected with a protection group, or a pharmaceutically acceptable salt thereof.

[0504] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound is described in Table Y or a compound in Table Y, wherein one or more the moieties in the compound (e.g., -OH) are protected with a protection group, or a stereoisomer thereof.

[0505] In some embodiments, the Saccharide-Based Ligand Scaffold is a compound is described in Table Y or a compound in Table Y, wherein one or more the moieties in the compound (e.g., -OH) are protected with a protection group.

[0506] In some embodiments, the Saccharide-Based Ligand Scaffold is a stereoisomer of a compound described in Table Y or of a compound in Table Y, wherein one or more the moieties in the compound (e.g., -OH) are protected with a protection group.

[0507] In some embodiments, the Saccharide-Based Ligand Scaffold is a pharmaceutically acceptable salt of a compound described in Table Y or of a compound in Table Y, wherein one or more the moieties in the compound (e g., -OH) are protected with a protection group.Variable B

[0508] In some embodiments, B is H.

[0509] In some embodiments, B is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0510] In some embodiments, B is methyl, ethyl, or propyl.

[0511] In some embodiments, B is a nucleobase moiety.

[0512] The term, “nucleobase moiety”, as used herein, refers to a nucleobase that is attached to the rest of the compound, e.g., via an atom of the nucleobase or a functional group thereof.

[0513] In some embodiments, the nucleobase moiety is adenine (A), cytosine (C), guanine (G), thymine (T), or uracil (U).the Saccharide-Based Ligand Agent or Saccharide-Based Ligand Unit.

[0515] In some embodiments, the nucleobase moiety is a modified nucleobase.

[0516] In some embodiments, the modified nucleobase is 5-methylcytosine.

[0517] In some embodiments, the modified nucleobase is hypoxanthine, xanthine, or 7- niethylguanine.

[0518] In some embodiments, the modified nucleobase is 5,6-dihydrouracil, 5-methylcytosine, or 5-hydroxymethylcytosine.

[0519] In some embodiments, the nucleobase moiety is an artificial nucleobase.

[0520] In some embodiments, the artificial nucleobase is isoguanine, isocytosine, 2-amino-6-(2- thienyl)purine, or pyrrole-2-carbaldehyde.Variables V and R

[0521] In some embodiments, V is -O-.

[0522] In some embodiments, V is -NRV~.

[0523] In some embodiments, V is -NH-.

[0524]

[0525]

[0526]

[0527]

[0528] In some embodiments, at least one RVis C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-buty I, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0529] In some embodiments, at least one Rvis C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0530] In some embodiments, at least one is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0531] In some embodiments, each Rvis C1-C6alkyl (e g., methyl, ethyl, n-propyl, i-propyl, n- butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I)

[0532] In some embodiments, each Rvis Cf-Ce alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n- butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0533] In some embodiments, each Rvis C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n- butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g , F, Cl, Br, or I).

[0534] In some embodiments, X is H.

[0535] In some embodiments, X is halogen (e g., F, Cl, Br, or I).

[0536] In some embodiments, X is F or Cl.

[0537] In some embodiments, X is F.

[0538] In some embodiments, X is -ORX

[0539] In some embodiments, X is -OH

[0540] In some embodiments, X is -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more RXa

[0541] In some embodiments, X is -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0542] In some embodiments, X is -OCH3.

[0543] In some embodiments, X is -O-(C1-C6alkyl)-O-(C1-C6alkyl) (e.g., wherein each C1-C6alkyl is independently methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0544] In some embodiments, X is -OCH2CH2OCH3.

[0545] In some embodiments, X is -O-(C1-C6alkyl)-(C6-Cio aryl) optionally substituted with one or more RXa.

[0546] In some embodiments, X is -O-(C1-C6alkyl)-(C6-Cio aryl).

[0547] In some embodiments,

[0548] In some embodiments, X isoptionally substituted with one or more R

[0549] In some embodiments, X isoptionally substituted with one or more halogen.

[0550] In some embodiments, X isoptionally substituted with one or more Ci-C6alkyl or -0-(C1-C6alkyl), wherein the C1-C6alkyl or -0-(Ct-C6 alkyl) is optionally substituted with one or more halogen.

[0551] In some embodiments, R? is H.

[0552] In some embodiments, Rxis C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more RXa.

[0553] In some embodiments, Rxis Ci-C’g alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I) or -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen.

[0554] In some embodiments, Rxis Ci-Cb alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl)

[0555] In some embodiments, Rxis methyl, ethyl, or propyl

[0556] In some embodiments, Rxis methyl.

[0557] In some embodiments, Rxis C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0558] In some embodiments, Rxis C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more -O-(C1-C6alkyl) (e g., wherein the C1-C6, alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl), wherein the -0-(CJ-C6 alkyl) is optionally substituted with one or more halogen.

[0559] In some embodiments, Rxis -(C1-C6alkyl)-(C6-C10aryl) optionally substituted with one or more RXa.

[0560] In some embodiments, RAis -(C1-C6alkyl)-(C6-C10aryl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I), C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n- butyi, i-butyl, s-butyl, t-butyl, pentyl, or hexyl), or -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl), wherein the C1-C6alkyl or -O-(C1-C6alkyl) is optionally substituted with one or more halogen.

[0561] In some embodiments, Rxis -(C1-C6alkyl)-(C6-Cio aryl).

[0562] In some embodiments, Rxand R4together form C1-C6alkylene (e.g., methylene, ethylene, propylene, butylene, pentylene, or hexylene).

[0563] In some embodiments, Rxand R4together form methylene, ethylene, or propylene

[0564] In some embodiments, Rxand R4together form methylene.

[0565] In some embodiments, Rxand R4together form ethylene.

[0566] In some embodiments, Rxand R4together form propylene.

[0567] In some embodiments, at least one RXais halogen (e.g., F, Cl, Br, or I).

[0568] In some embodiments, at least one RXais F or Cl.

[0569] Ln some embodiments, at least one RXais F.

[0570] In some embodiments, at least one RXais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0571] In some embodiments, at least one RXais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0572] In some embodiments, at least one RXais -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0573] In some embodiments, at least one RXais -O-(C1-C6alkyl) (e.g., wherein the C1-C6alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0574] In some embodiments, Y is H.

[0575] In some embodiments, Y is C1-C6, alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i- butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0576] In some embodiments, Y is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i- butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0577] In some embodiments, Y is methyl, ethyl, or propyl.

[0578] In some embodiments, Y is -P(R ' R -P(ORY)(N(RY)2), ~P(-O)(ORY)RY, -P( S)(OlV )R ’ , -P(=O)(SRY)RY, -P(=S)(SRY)RY, -P(=O)(ORY)2, -P(=S)(ORY)2, -P(=O)(SRY)2, or -P(=S)(SRY)2.

[0579] In some embodiments, Y is -PfR1)2-

[0580] In some embodiments, Y is -PH?..

[0581] In some embodiments, Y is -P(OR’1)(N(RY)2).

[0582] In some embodiments, Y is -P(OH)(NH2).

[0583] In some embodiments, Y is -P(O(C1-C6alkyl))(N(C1-C6alkyl)2), wherein each C1-C6alkyl is independently optionally substituted with one or more halogen or cyano.

[0584] In some embodiments, Y is -P(=O)(OR')RV.

[0585] In some embodiments, Y is -P(=O)(OH)(C1-C6alkyl), wherein the C1-C6alkyl is optionally substituted with one or more halogen or cyano.

[0586] In some embodiments, Y is -P(=S)(()RV)RV.

[0587] In some embodiments, Y is -P(=S)(OH)(CI-C6 alkyl), wherein the C1-C6alkyl is optionally substituted with one or more halogen or cyano.

[0588] In some embodiments, ¥ is -P(=O)(SRY)RX.

[0589] In some embodiments, Y is -P(=O)(SH)(CI-C6 alkyl), wherein the C1-C6alkyl is optionally substituted with one or more halogen or cyano.

[0590] In some embodiments, Y is -P(==S)(SR^)RV.

[0591] In some embodiments, Y is -P(=S)(SH)(CI-C6 alkyl), wherein the C1-C6alkyl is optionally substituted with one or more halogen or cyano.

[0592] In some embodiments, Y is -P(::=O)(ORVh.

[0593] In some embodiments, Y is -P(=O)(OH)2.

[0594] In some embodiments, Y is -P(===S)(ORY)2.

[0595] In some embodiments, Y is -P(=S)(OH)2.

[0596] In some embodiments, Y is -P(=O)(SRY)2.

[0597] In some embodiments, Y is -P(=O)(SH)2.

[0598] In some embodiments, Y is -P(=S)(SB?)2.

[0599] In some embodiments, Y is -P(=S)(SH)2.

[0600] In some embodiments, Y is a hydroxy protecting group.

[0601] In some embodiments, Y is silyl (e.g., trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, tert-butyl diphenyl silyl, or triisopropylsilyl).

[0602] In some embodiments, Y is triphenylmethyl (Tr) or 4,4'-dimethoxytrityl (DMTr).

[0603] In some embodiments, Y is optionally substituted acyl (e.g., optionally substituted acetyl) or benzyl .

[0604] In some embodiments, at least one RYis H.

[0605] In some embodiments, each RYis H.

[0606] In some embodiments, at least one Rvis C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I) or cyano.

[0607] In some embodiments, each Rvis C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n- butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g , F, Ci, Br, or I) or cyano

[0608] In some embodiments, at least one R‘ is H, and at least one RYis C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen or cyano.

[0609] In some embodiments, when X is -OH, then Y is not H or a hydroxy protecting group.

[0610] In some embodiments, when X is -Oil, then Y is C1-C6alkyl optionally substituted with

[0611] In some embodiments, when Y is H or a hydroxy protecting group, then X is not -OH.

[0612] In some embodiments, when Y is H or a hydroxy protecting group, then X is H, halogen, or -ORX, and RAis C1-C6alkyl or -(C1-C6alkyl)-(C6-Cio aryl), wherein the C1-C6alkyl or -(Ci- Ce alkyl)-(C6-Cio aryl) is optionally substituted with one or more RXa.

[0613] In some embodiments, Z is H

[0614] In some embodiments, Z is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i- butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).y p y y

[0641] In some embodiments, Z is triphenylmethyl (Tr) or 4,4'-dimethoxytrityl (DMTr).

[0642] In some embodiments, Z is substituted acyl (e.g., optionally substituted acetyl) or benzyl.

[0643] In some embodiments, at least one Rzis H.

[0644] In some embodiments, each Rzis II.

[0645] In some embodiments, at least one Rzis C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I) or cyano.

[0646] In some embodiments, each Rzis C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n- butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I) or cyano.Variables R:\ R], R2, R3, R4, R5, and n[066.3] In some embodiments, each Rais FI.

[0664] In some embodiments, at least one Rais H

[0665] In some embodiments, at least one R3is halogen (e g , F, Cl, Br, or I) or C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0666] In some embodiments, at least one Rais halogen (e.g., F, Cl, Br, or I).

[0667] In some embodiments, at least one R3is F or Cl.

[0668] In some embodiments, at least one Rais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0669] In some embodiments, at least one Rais Ci-C« alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl)

[0670] In some embodiments, at least one Rais C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0671] In some embodiments, two vicinal Raform a bond.

[0672] In some embodiments, R1is H.

[0673] In some embodiments, R!is halogen (e.g., F, Cl, Br, or I).

[0674] In some embodiments, R‘ is F or Cl.

[0675] In some embodiments, R' is , alkCy1l-C (6e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0676] In some embodiments, R1is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0677] In some embodiments, R1is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0678] In some embodiments, Rzis H.

[0679] In some embodiments, Rzis halogen (e.g., F, Cl, Br, or I).

[0680] In some embodiments, R2is F or Cl.

[0681] In some embodiments, R2is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0682] In some embodiments, R2is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0683] Ln some embodiments, R2is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0684] In some embodiments, R3is H.

[0685] In some embodiments, R3is halogen (e.g., F, Cl, Br, or I).

[0686] In some embodiments, R3is F or Cl.

[0687] In some embodiments, R3is C1-C6, alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0688] In some embodiments, R3is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0689] In some embodiments, R3is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0690] In some embodiments, R4is H.

[0691] In some embodiments, R4is halogen (e.g., F, Cl, Br, or I).

[0692] In some embodiments, R4is F or Cl.

[0693] In some embodiments, R4is C1-C6alkyl (e g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0694] In some embodiments, R4is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl).

[0695] In some embodiments, R4is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0696] In some embodiments, R4and Rxtogether form C1-C6alkylene (e.g., methylene, ethylene, propylene, butylene, pentylene, or hexylene).

[0697] In some embodiments, R4and Rxtogether form methylene, ethylene, or propylene.

[0698] In some embodiments, R4and Rxtogether form methylene.

[0699] In some embodiments, R4and Rxtogether form ethylene.

[0700] In some embodiments, R4and Rxtogether form propylene.

[0701] Ln some embodiments, each R3is H.

[0702] In some embodiments, at least one R3is H.

[0703] In some embodiments, at least one R3is halogen (e.g., F, Cl, Br, or I) or C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyi, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0704] In some embodiments, at least one R5is halogen (e g., F, Cl, Br, or I).

[0705] In some embodiments, at least one R5is F or Cl.

[0706] In some embodiments, at least one R3is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) optionally substituted with one or more halogen (e.g., F, Cl, Br, or I).

[0707] In some embodiments, at least one R5is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl)

[0708] In some embodiments, at least one R3is C1-C6alkyl (e.g., methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, or hexyl) substituted with one or more halogen (e.g , F, Cl, Br, or I).

[0709] In some embodiments, each of R\ R1, R2, R3, R4, and R5is H.

[0710] In some embodiments, n is an integer ranging from about 1 to about 10.

[0711] In some embodiments, n is an integer ranging from about 2 to about 10

[0712] In some embodiments, n is an integer ranging from about 3 to about 10, from about 4 to about 10, from about 5 to about 10, or from about 6 to about 10.

[0713] In some embodiments, n is an integer ranging from about 1 to about 8, from about 1 to about 7, from about 1 to about 6, from about 1 to about 5, from about 1 to about 4, or from about1 to about 3.

[0714] In some embodiments, n is an integer ranging from about 2 to about 8, from about 2 to about 7, from about 2 to about 6, from about 2 to about 5, from about 2 to about 4, or from about2 to about 3.

[0715] In some embodiments, n is 0.

[0716] In some embodiments, n is 1.

[0717] In some embodiments, n is 2

[0718] In some embodiments, n is 3.

[0719] In some embodiments, n is 4.

[0720] Ln some embodiments, n is 5.

[0721] In some embodiments, n is 6.

[0722] In some embodiments, n is 7.

[0723] In some embodiments, n is 8.

[0724] In some embodiments, n is 9

[0725] In some embodiments, n is 10Exemplary Embodiments of the Saccharide-Based Ligand Agents

[0726] In some embodiments, the Saccharide-Based Ligand Agent is a compound of Formula

[0727] In some embodiments, the Saccharide-Based Ligand Agent is a compound of Formula (I- A), (II- A), (III- A), or (IV- A):[0 / 28] In some embodiments, the Saccharide-Based Ligand Agent is a compound of Formula[0 / 29] In some embodiments, the Saccharide-Based Ligand Agent is a compound of Formula ( I -B), (II-B), (III-B), or (IV-B):

[0730] In some embodiments, the Saccharide-Based Ligand Agent is a compound of Formula

[0731] In some embodiments, the Saccharide-Based Ligand Agent is a compound of Formula (I-C), (II-C), (III-C), (TV-C), (V-C), (VI-C), (VII-C), or (VIII-C):[0 / 32] In some embodiments, the Saccharide-Based Ligand Agent is a compound of Formula

[0733] In some embodiments, the Saccharide-Based Ligand Agent is:of a pharmaceutically acceptable salt thereof, wherein:each Rzindependently is H or C1-C6alkyl optionally- substituted with one or more halogen or cyano.

[0734] In some embodiments, the Saccharide-Based Ligand Agent is selected from the compounds described in Table L and pharmaceutically acceptable salts thereof.

[0735] In some embodiments, the Saccharide-Based Ligand Agent is selected from the compounds described in Table L.Table Lwherein variables L and B are as described herein, and R1 ;;is -OH or -OMe.

[0736] In some embodiments, R: !is -OH

[0737] In some embodiments, R''3is -OMe.

[0738] In some embodiments, the Saccharide-Based Ligand Agent is selected from L-l, L-2, and L-3 and pharmaceutically acceptable salts thereof.

[0739] In some embodiments, the Saccharide-Based Ligand Agent is L-l or a pharmaceutically acceptable salt thereof. In some embodiments, the Saccharide-Based Ligand Agent is L-2 or a pharmaceutically acceptable salt thereof. In some embodiments, the Saccharide-Based Ligand Agent is L-3 or a pharmaceutically acceptable salt thereof,

[0740] In some embodiments, the Saccharide-Based Ligand Agent is selected from L-l, L-2, and L-3.

[0741] In some embodiments, the Saccharide-Based Ligand Agent is L-l. In some embodiments, the Saccharide-Based Ligand Agent is L-2. In some embodiments, the Saccharide-Based Ligand Agent is L-3

[0742] In some embodiments, the Saccharide-Based Ligand Agent is selected from the compounds described in Table L (e.g., any one of L-l to L-68), wherein, as applicable, the protected hydroxy group(s) at the 3’- and / or 5’-position(s) exist in the unprotected form, i.e., OH, and pharmaceutically acceptable salts thereof.

[0743] In some embodiments, the Saccharide-Based Ligand Agent is selected from the compounds described in Table L (e.g., any one of L-l to L-68), wherein, as applicable, the protected hydroxy group(s) at the 3’- and / or 5’-position(s) exist in the unprotected form, i.e., OH.

[0744] In some aspects, the present disclosure provides an isotopic derivative (e g., isotopically labeled compound) of a Saccharide-Based Ligand Scaffold disclosed herein.

[0745] In some aspects, the present disclosure provides an isotopic derivative (e.g , isotopically labeled compound) of a Saccharide-Based Ligand Agent disclosed herein.

[0746] In some aspects, the present disclosure provides an isotopic derivative (e.g., isotopically labeled compound) of a Saccharide-Based Ligand disclosed herein.

[0747] In some aspects, the present disclosure provides an isotopic derivative (e.g., isotopically labeled compound) of a Saccharide-Based Ligand Unit disclosed herein.

[0748] In some aspects, the present disclosure provides an isotopic derivative (e.g., isotopically labeled compound) of a compound disclosed herein.

[0749] In some aspects, the present disclosure provides an isotopic derivative (e g , isotopicallylabeled compound) of a conjugate disclosed herein

[0750] It is understood that the isotopic derivative can be prepared using any of a variety of art- recognized techniques. For example, the isotopic derivative can generally be prepared by carrying out the procedures disclosed in the Schemes and / or in the Examples herein, by substituting an isotopically labeled reagent for a non-isotopically labeled reagent.

[0751] In some embodiments, the isotopic derivative is a deuterium labeled derivative.

[0752] The term “isotopic derivative”, as used herein, refers to a derivative of a chemical structure in which one or more atoms are isotopically enriched or labelled. For example, an isotopic derivative of an agent is isotopically enriched with regard to, or labelled with, one or more isotopes as compared to the corresponding agent. In some embodiments, the isotopic derivative is enriched with regard to, or labelled with, one or more atoms selected from2H,i3C,14C,15N,18O,29Si,32P, andj4S Tn some embodiments, the isotopic derivative is a deuterium labeled derivative (i.e., being enriched with2H with regard to one or more atoms thereof). In some embodiments, the derivative is a2H labeled derivative In some embodiments, the derivative is a13C labeled derivative or a14C labeled derivative. In some embodiments, the derivative is a1 SF labeled derivative. In some embodiments, the derivative is a ’!ZT labeled derivative, a, 241 labeled derivative, a125I labeled derivative, a129l labeled derivative, a!’!I labeled derivative, al35I labeled derivative, or any combination thereof. In some embodiments, the derivative is a15P labeled derivative or a32P labeled derivative, fa some embodiments, the derivative is a33S labeled derivative, aj4S labeled derivative, a33S labeled derivative, a3cS labeled derivative, or any combination thereof.

[0753] It is understood that the isotopic derivatives can be prepared using any of a variety' of art- recognized techniques. For example, the isotopic derivatives can generally be prepared by carrying out the procedures disclosed in the Schemes and / or in the Examples described herein, by substituting an isotope labeled reagent for a non-isotope labeled reagent.

[0754] It is also understood that isotopical substitution may afford certain therapeutic advantages resulting from greater metabolic stability, e.g,, increased in vivo half-life or reduced dosage requirements.

[0755] For the avoidance of doubt it is to be understood that, where in this specification a group is qualified by “described herein”, the said group encompasses the first occurring and broadest definition as well as each and all of the particular definitions for that group.

[0756] Values may be expressed as approximations by the use of the antecedent '‘about” or as a range with the use of “±”. When values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. As used herein, “about X” {where X is a numerical value) preferably refers to ±10%, ±5%, ±4%, ±3%, ±2%, or ±1% of the recited value, inclusive. It should be understood that, unless clearly indicated to the contrary', the disclosure of numerical values and ranges of numerical values in the specification includes both i) the exact value(s) or range specified, and ii) values that are “about” the value(s) or ranges specified (e g., values or ranges falling within a reasonable range.

[0757] In some embodiments, “about X” refers to ±10% of the recited value, inclusive.

[0758] In some embodiments, “about X” refers to ±5% of the recited value, inclusive.

[0759] In some embodiments, “about X” refers to ±4% of the recited value, inclusive.

[0760] In some embodiments, “about X” refers to ±3% of the recited value, inclusive.

[0761] In some embodiments, “about X” refers to ±2% of the recited value, inclusive.

[0762] In some embodiments, “about X” refers to ±1% of the recited value, inclusive.

[0763] It will be understood that while compounds disclosed herein may be presented in one particular configuration. Such particular configuration is not to be construed as limiting the disclosure to one or another isomer, tautomer, regioisomer or stereoisomer, nor does it exclude mixtures of isomers, tautomers, regioisomers or stereoisomers. In some embodiments, the presentation of a compound herein in a particular configuration intends to encompass, and to refer to, each of the available isomers, tautomers, regioisomers, and stereoisomers of the compound, or any mixture thereof; while the presentation further intends to refer to the specific configuration of the compound.

[0764] It will be understood that while compounds disclosed herein may be presented without specified configuration (e.g., without specified stereochemistry). Such presentation intends to encompass all available isomers, tautomers, regioisomers, and stereoisomers of the compound. In some embodiments, the presentation of a compound herein without specified configuration intends to refer to each of the available isomers, tautomers, regioisomers, and stereoisomers of the compound, or any mixture thereof.

[0765] ,4s used herein, the term “isomerism” means compounds that have identical molecular formulae but differ in the sequence of bonding of their atoms or in the arrangement of their atoms in space. Compounds that have the same molecular formula but differ in the nature orsequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”. Stereoisomers that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers”. When a compound has an asymmetric center, for example, it is bonded to four different groups, a pair of enantiomers is possible. An enantiomer can be characterised by the absolute configuration of its asymmetric center and is described by the R~ and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+) or (-)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”.

[0766] The compounds of this disclosure may possess one or more asymmetric centers; such compounds can therefore be produced as individual (R)- or (S)-stereoi somers or as mixtures thereof. Unless indicated otherwise, the description or naming of a particular compound in the specification and claims is intended to include both individual enantiomers and mixtures, racemic or otherwise, thereof. The methods for the determination of stereochemistry' and the separation of stereoisomers are well-known in the art, for example by synthesis from optically active starting materials or by resolution of a racemic form. Some of the compounds of the disclosure may have geometric isomeric centers (E- and Z- isomers). It is to be understood that the present disclosure encompasses all optical, diastereoisomers and geometric isomers and mixtures thereof that possess the biological activity defined herein.

[0767] As used herein, the term “chiral center” refers to a carbon atom bonded to four nonidenti cal substituents.

[0768] As used herein, the term “chiral isomer” means a compound with at least one chiral center. Compounds with more than one chiral center may exist either as an individual diastereomer or as a mixture of diastereomers, termed “diastereomeric mixture.” When one chiral center is present, a stereoisomer may be characterized by the absolute configuration (R or S) of that chiral center. Absolute configuration refers to the arrangement in space of the substituents attached to the chiral center. The substituents attached to the chiral center under consideration are ranked in accordance with the Sequence Rule of Cahn, Ingold and Prelog, as known in the art.

[0769] As used herein, the term “geometric isomer” means the diastereomers that owe their existence to hindered rotation about double bonds or a cycloalkyl linker (e.g., 1,3-cyclobutyl). These configurations are differentiated in their names by the prefixes cis and trans, or Z and E, which indicate that the groups are on the same or opposite side of the double bond in the molecule according to the Cahn-Ingold-Prelog rules.

[0770] It is to be understood that the compounds of the present disclosure may be depicted as different chiral isomers or geometric isomers. It is also to be understood that when compounds have chiral isomeric or geometric isomeric forms, all isomeric forms are intended to be included in the scope of the present disclosure, and the naming of the compounds does not exclude any isomeric forms, it being understood that not all isomers may have the same level of activity.

[0771] It is to be understood that the structures and other compounds discussed in this disclosure include all atropic isomers thereof. It is also to be understood that not all atropic isomers may have the same level of activity.

[0772] As used herein, the term “atropic isomers” are a type of stereoisomer in which the atoms of two isomers are arranged differently in space. Atropic isomers owe their existence to a restricted rotation caused by hindrance of rotation of large groups about a central bond. Such atropic isomers typically exist as a mixture, however as a result of recent advances in chromatography techniques, it has been possible to separate mixtures of two atropic isomers in select, cases.

[0773] As used herein, the term “tautomer” is one of two or more structural isomers that exist in equilibrium and is readily converted from one isomeric form to another This conversion results in the formal migration of a hydrogen atom accompanied by a swatch of adjacent conjugated double bonds. Tautomers exi st as a mixture of a tautomeric set in solution. In solutions where tautomerization is possible, a chemical equilibrium of the tautomers will be reached. The exact ratio of the tautomers depends on several factors, including temperature, solvent and pH. The concept of tautomers that are interconvertible by tautomerizations is called tautomerism. Of the various types of tautomerism that are possible, two are commonly observed. In keto-enol tautomerism a simultaneous shift of electrons and a hydrogen atom occurs. Ring-chain tautomerism arises as a result of the aldehyde group (-CHO) in a sugar chain molecule reacting with one of the hydroxy groups (-OH) in the same molecule to give it a cyclic (ring-shaped) form as exhibited by glucose

[0774] It is to be understood that the compounds of the present disclosure may be depicted as different tautomers. It should also be understood that when compounds have tautomeric forms, all tautomeric forms are intended to be included in the scope of the present disclosure, and the naming of the compounds does not exclude any tautomer form. It will be understood that certain tautomers may have a higher level of activity than others.

[0775] It is to be understood that the compounds of any Formula described herein include the compounds themselves, as well as their salts, and their solvates, if applicable. A salt, for example, can be formed between an anion and a positively charged group (e.g., amino) on a substituted compound disclosed herein. Suitable anions include chloride, bromide, iodide, sulfate, bisulfate, sulfamate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate, glutamate, glucuronate, glutarate, malate, maleate, succinate, fumarate, tartrate, tosylate, salicylate, lactate, naphthalenesulfonate, and acetate (e.g , trifluoroacetate).

[0776] As used herein, the term ‘"pharmaceutically acceptable anion” refers to an anion suitable for forming a pharmaceutically acceptable salt. Likewise, a salt can also be formed between a cation and a negatively charged group (e.g., carboxylate) on a substituted compound disclosed herein. Suitable cations include sodium ion, potassium ion, magnesium ion, calcium ion, and an ammonium cation such as tetramethylammonium ion or diethylammonium ion. The substituted compounds disclosed herein also include those salts containing quaternary' nitrogen atoms.

[0777] It is to be understood that the compounds of the present disclosure, for example, the salts of the compounds, can exist in either hydrated or unhydrated (the anhydrous) form or as solvates with other solvent molecules. Nonlimiting examples of hydrates include monohydrates, dihydrates, etc. Nonlimiting examples of solvates include ethanol solvates, acetone solvates, etc.

[0778] As used herein, the term “solvate” means solvent addition forms that contain either stoichiometric or non- stoichiometric amounts of solvent. Some compounds have a tendency to trap a fixed molar ratio of solvent molecules in the crystalline solid state, thus forming a solvate.If the solvent is water the solvate formed is a hydrate; and if the solvent is alcohol, the solvate formed is an alcoholate. Hydrates are formed by the combination of one or more molecules of water with one molecule of the substance in which the water retains its molecular state as H2O.

[0779] As used herein, the term “analog” refers to a chemical compound that is structurally similar to another but differs slightly in composition (as in the replacement of one atom by an atom of a different element or in the presence of a particular functional group, or the replacementof one functional group by another functional group) Thus, an analog is a compound that is similar or comparable in function and appearance, but not in structure or origin to the reference compound.

[0780] As used herein, the term ‘‘derivative” refers to compounds that have a common core structure and are substituted with various groups as described herein.

[0781] As used herein, the term “bioisostere” refers to a compound resulting from the exchange of an atom or of a group of atoms with another, broadly similar, atom or group of atoms. The objective of a bioisosteric replacement is to create a new compound with similar biological properties to the parent compound. The bioisosteric replacement may be physicochemically or topologically based. Examples of carboxylic acid bioisosteres include, but are not limited to, acyl sulfonamides, tetrazoles, sulfonates and phosphonates. See, e.g., Patani and LaVoie, Chem. Rev. 96, 3147-3176, 1996.

[0782] It is also to be understood that certain compounds of any one of the Formulae disclosed herein may exist in solvated as well as unsolvated forms such as, for example, hydrated forms. A suitable pharmaceutically acceptable solvate is, for example, a hydrate such as hemi -hydrate, a mono-hydrate, a di-hydrate or a tri-hydrate. It is to be understood that the disclosure encompasses all such solvated forms that possess the biological activity defined herein.

[0783] It is also to be understood that certain compounds of any one of the Formulae disclosed herein may exhibit polymorphism, and that the disclosure encompasses all such forms, or mixtures thereof, which possess the biological activity defined herein. It is generally known that crystalline materials may be analysed using conventional techniques such as X-Ray Powder Diffraction analysis, Differential Scanning Calorimetry, Thermal Gravimetric Analysis, Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy, Near Infrared (NIR) spectroscopy, solution and / or solid state nuclear magnetic resonance spectroscopy. The water content of such crystalline materials may be determined by Karl Fischer analysis.

[0784] Compounds of any one of the Formulae disclosed herein may exist in a number of different tautomeric forms and references to compounds of any one of the Formulae include all such forms. For the avoidance of doubt, where a compound can exist in one of several tautomeric forms, and only one is specifically described or shown, all others are nevertheless embraced by the Formulae disclosed herein. Examples of tautomeric forms include keto-, enol-, and enolate- forms, as in, for example, the following tautomeric pairs: keto / enol (illustrated below),imine / enamine, amide / imino alcohol, amidine / amidine, nitroso / oxime, thioketone / enethiol, and nitro / aci -nitro.

[0785] Compounds of any one of the Formulae disclosed herein containing an amine function may also form N-oxides. A reference herein to a compound of any one of the Formulae herein that contains an amine function also includes the N-oxide. Where a compound contains several amine functions, one or more than one nitrogen atom may be oxidized to form an N-oxide. Particular examples of N-oxides are the N-oxides of a tertiary' amine or a nitrogen atom of a nitrogen-containing heterocycle. N-oxides can be formed by treatment of the corresponding amine with an oxidizing agent such as hydrogen peroxide or a peracid (e.g. a peroxycarboxylic acid), in which the amine compound is reacted with meta-chloroperoxybenzoic acid (mCPBA), for example, in an inert solvent such as dichloromethane.

[0786] The compounds of any one of the Formulae disclosed herein may be administered in the form of a prodrug which is broken down in the human or animal body to release a compound of the disclosure. A prodrug may be used to alter the physical properties and / or the pharmacokinetic properties of a compound of the disclosure. A prodrug can be formed when the compound of the disclosure contains a suitable group or substituent to which a property-modifying group can be attached.

[0787] .Accordingly, the present disclosure includes those compounds of any one of the Formulae disclosed herein as defined hereinbefore when made available by organic synthesis and when made available within the human or animal body by way of cleavage of a prodrug thereof. Accordingly, the present disclosure includes those compounds of any one of the Formulae disclosed herein that are produced by organic synthetic means and also such compounds that are produced in the human or animal body by way of metabolism of a precursor compound, that is a compound of any one of the Formulae disclosed herein may be a synthetically-produced compound or a metabolically-produced compound.

[0788] A suitable pharmaceutically acceptable prodrug of a compound of any one of the Formulae disclosed herein is one that is based on reasonable medical judgment as being suitablefor administration to the human or animal body without undesirable pharmacological activities and without undue toxicity. Various forms of prodrug have been described and are well-known in the art.

[0789] The in vivo effects of a compound of any one of the Formulae disclosed herein may be exerted in part by one or more metabolites that are formed within the human or animal body after administration of a compound of any one of the Formulae disclosed herein. As stated hereinbefore, the in vivo effects of a compound of any one of the Formulae disclosed herein may also be exerted by way of metabolism of a precursor compound (a prodrug).

[0790] Suitably, the present disclosure excludes any individual compounds not possessing the biological activity defined herein.Conjugates Comprising Saccharide-Based Ligands .and / or Saccharide-Based Ligand Units

[0791] As used herein, the term ‘"conjugate” refers to a compound or complex that comprises a Nucleic Acid Agent being covalently attached to a ligand (e.g., Saccharide-Based Ligand). In some embodiments, the conjugate comprises one or more Saccharide-Based Ligand (i.e., variable L) described herein. In some embodiments, the conjugate comprises one or more Saccharide-Based Ligand Unit described herein In some embodiments, the conjugate is prepared from one or more compound (e.g., Saccharide-Based Ligand, Saccharide-Based Ligand Agent, or Saccharide-Based Ligand Scaffold) described herein.

[0792] In some aspects, the present disclosure provides a conjugate or a pharmaceutically acceptable salt thereof, comprising:(!) one or more Nucleic Acid Agent; and(ii) one or more Saccharide-Based Ligand, each independently being L, wherein variable L is described herein.

[0793] In some aspects, the present disclosure provides a conjugate or a pharmaceutically acceptable salt thereof, comprising:(i) one or more Nucleic Acid Agent; and(ii) one or more Saccharide-Based Ligand Unit, wherein each Saccharide-Based Ligand Unit independently is:wherein: variables L, B, V, X, Ra, n, Rv, Rx, RXa, Rv, Rz', R1, R2, R3, R4, and R5are described herein, and when the Saccharide-Based Ligand Unit is at the 3 ’-terminus of the Nucleic Acid Agent,# is an attachment to the rest of the conjugate; andwhen the Saccharide-Based Ligand Unit is at the 5 ’-terminus of the Nucleic Acid Agent, RZ)RZ, -hydroxy protecting group, and## is an attachment to the rest of the conjugate; or each of # and ## independently is an attachment to the rest of the conjugate

[0794] It is understood that the one or more Saccharide-Based Ligand and / or one or more Saccharide-Based Ligand Unit each independently is attached to a terminal position or an internal position of the one or more Nucleic Acid Agent. Further, it is understood that, when a Nucleic Acid Agent comprises more than one strand (e.g., a sense strand and an antisensestrand), the one or more Saccharide-Based Ligand and / or one or more Saccharide-Based Ligand Unit could be attached to the same strand, or different strands, of the Nucleic Acid Agent.

[0800] In some embodiments, the conjugate further comprises one or more Linker Unit.

[0801] In some embodiments, the conjugate comprises a double strand RNA (e.g., double strand siRNA), one or more Saccharide-Based Ligand, and one or more Saccharide-Based Ligand Unit.

[0802] In some embodiments, one or more Saccharide-Based Ligand Unit is attached to the Nucleic Acid Agent (e.g., siRNA) directly.

[0803] In some embodiments, one or more Saccharide-Based Ligand Unit is attached to the Nucleic Acid Agent (e.g., siRNA) via one or more Linker Unit.

[0804] In some embodiments, one or more Saccharide-Based Ligand Unit is attached to the Nucleic Acid Agent (e.g., siRNA) via one or more Saccharide-Based Ligand.

[0805] In some embodiments, one or more Saccharide-Based Ligand Unit is attached to the Nucleic Acid Agent (e.g., siRNA) via one or more Saccharide-Based Ligand and one or more Linker Unit.

[0806] In some embodiments, one or more Saccharide-Based Ligand is attached to the Nucleic Acid Agent (e.g., siRNA) directly.

[0807] In some embodiments, at least one Saccharide-Based Ligand is attached to the Nucleic Acid Agent (e.g., siRNA) via one or more Linker Unit.

[0808] In some embodiments, at least one Saccharide-Based Ligand is attached to the Nucleic .Acid Agent (e.g , siRNA) via a Saccharide-Based Ligand Unit.

[0809] In some embodiments, at least one Saccharide-Based Ligand is attached to Saccharide- Based Ligand Unit directly.

[0810] In some embodiments, at least one Saccharide-Based Ligand is attached to Saccharide- Based Ligand Unit via a Linker Unit.

[0811] In some embodiments, at least one Saccharide-Based Ligand is attached to the Nucleic Acid Agent (e.g., siRNA) via a Saccharide-Based Ligand Unit and a Linker Unit.

[0812] In some embodiments, at least one Saccharide-Based Ligand Unit is attached to the antisense or sense strand of the Nucleic Acid Agent (e.g., siRNA) directly or via a Linker Unit.

[0813] In some embodiments, at least one Saccharide-Based Ligand Unit is attached to the antisense strand of the Nucleic Acid Agent (e.g., siRNA) directly or via a Linker Unit.

[0814] In some embodiments, at least one Saccharide-Based Ligand Unit is attached to the sense strand of the Nucleic Acid Agent (e.g., siRNA) directly or via a Linker Unit.

[0815] In some embodiments, at least one Saccharide-Based Ligand Unit is attached to a terminal position (e.g., a nucleotide at the 3 ’-end or the 5 ’-end) or internal position (e.g , a nucleotide that is not at the 3 ’-end or the 5 ’-end) of the sense or antisense strand of the Nucleic Acid Agent (e.g., siRNA) directly or via a Linker Unit.

[0816] In some embodiments, at least one Saccharide-Based Ligand is attached to the antisense or sense strand of the Nucleic Acid Agent (e.g., siRNA) directly or via a Linker Unit.

[0817] In some embodiments, at least one Saccharide-Based Ligand is attached to the antisense strand of the Nucleic Acid Agent (e.g., siRNA) directly or via a Linker Unit.

[0818] In some embodiments, at least one Saccharide-Based Ligand is attached to the sense strand of the Nucleic Acid Agent (e.g., siRNA) directly or via a Linker Unit.

[0819] In some embodiments, at least one Saccharide-Based Ligand is attached to a terminal position (e.g., a nucleotide at the 3 ’-end or the 5’-end) or internal position (e.g., a nucleotide that is not at the 3 ’-end or the 5 ’-end) of the sense or antisense strand of the Nucleic Acid Agent (e.g., siRNA) directly or via a Linker Unit.

[0820] In some embodiments, the conjugate comprises:(Nucleic Acid Agent)- [(Linker Unit)o-i-( Saccharide-Based Ligand Unit)]i-3; or [(Saccharide-Based Ligand Unit)-(Linker Unit)o-i]i-3-(Nucleic Acid Agent)- [(Linker Unit)o-i-(Saccbaride-Based Ligand Unit)]i-3;wherein each of the Linker Unit and Saccharide-Based Ligand Unit, when attached to the Nucleic Acid Agent (e.g., siRNA), independently is attached to a terminal position (e.g., a nucleotide at the 3’-terminus or the 5’-terminus) or an internal position (e.g., a nucleotide that is not at the 3’-terminus or the 5’-terminus) of the Nucleic Acid Agent (e.g., siRNA).

[0821] In some embodiments, the conjugate comprises:(Nucleic Acid Agent)-[(Linker Unit)o-i-( Saccharide-Based Ligand)]]-?,; or[(Saccharide-Based Ligand)-(Linker Unit)o-i]i-3-(Nucleic Acid Agent)- [(Linker Unit)o-i- (Saccharide-Based Li gand)] 1-3 ; wherein each of the Linker Unit and Saccharide-Based Ligand, when attached to the Nucleic Acid Agent (e.g., siRNA), independently is attached to a terminal position (e.g., a nucleotide at the 3’-terminus or the 5’-terminus) or an internal position (e.g., a nucleotide that is not at the 3 ’-terminus or the 5 ’-terminus) of the Nucleic Acid Agent (e.g., siRNA)

[0822] In some embodiments, the conjugates comprise:wherein the Nucleic Acid Agent may optionally be further attached to one or more Linker Units, one or more Saccharide-Based Ligands, and / or one or more Saccharide-Based Ligand Units at one or more of the terminal positions (e.g., a nucleotide at the 3’-terminus or the 5’- terminus) and / or internal positions of the Nucleic Acid Agent according to the attachment described herein.

[0823] It is understood that the one or more attachments to the Nucleic Acid Agent may be atAcid Agent is independently attached at the antisense or sense strand of the Nucleic Acid Agent).

[0824] In some embodiments, the conjugate is selected from the conjugates described in FIG. 6, and pharmaceutically acceptable salts and stereoisomers thereof

[0825] In some embodiments, the conjugate is selected from the conjugates described in FIG. 6, and pharmaceutically acceptable salts thereof.

[0826] In some embodiments, the conjugate is selected from the conjugates described in FIG. 6.

[0827] In some embodiments, the conjugate is a pharmaceutically acceptable salt of a conjugate described in FIG. 6,

[0828] In some embodiments, the conjugate is a stereoisomer of a conjugate described in FIG.6.

[0829] In some embodiments, the conjugate is selected from the conjugates described in Table F, and pharmaceutically acceptable salts and stereoisomers thereof.

[0830] In some embodiments, the conjugate is selected from the conjugates described in Table F, and pharmaceutically acceptable salts thereof.

[0831] In some embodiments, the conjugate is selected from the conjugates described in Table F.

[0832] In some embodiments, the conjugate is a pharmaceutically acceptable salt of a conjugate described in Table F.

[0833] In some embodiments, the conjugate is a stereoisomer of a conjugate described in Table

[0834] In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is, or a pharmaceutically acceptable salt thereof.

[0835] In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is:

[0836] In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is selected from the structures described in Table C.Table C

[0837] In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is selected from C-l, C-2, C-3, C-4, C-5, and C-6.

[0838] In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is C-l In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is C-2. In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is C-3. In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is C-4. In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is C-5. In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is C-6.

[0839] In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is selected from the structures described in Table D.wherein variables L, B, and RU3are as described herein.

[0840] in some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is selected from D-l, D-2, and D-3.

[0841] In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is D-l In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is D-2. In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is D-3.

[0842] In some embodiments, at least one Saccharide-Based Ligand Unit in the conjugate is selected from G1b-Tris-Man3, Glb-Tris-Fuco3, Glb-Man-C5, G Ib-ser-Man, Glb-ser(Man-C5)- Man, Glb-ser(C6)-Man, Glb-PhC(S)NH2-Man, Glb-Tris-3 SulfoGai, Glb-ser(C12)-Man, Gl b- Gal-C5, Glb-ser(Man-PEG3)-Man, Glb-3NMC(TZ-C5), Glb-Man-C15, Glb-ManPEG4, and Glb-lysine-C 15-2N.MC.

[0843] In some embodiments, the conjugate comprises Glb-Tris-Man3 (e.g., at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent (e g., sense and / or antisense strand)).

[0844] In some embodiments, the conjugate comprises Glb-Tris-Fuco3 (e.g,, at the 5 ’-terminus, 3’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0845] In some embodiments, the conjugate comprises Glb-Man-C5 (e g., at the 5’-terminus, 3’- terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0846] In some embodiments, the conjugate comprises Glb-ser-Man (e.g., at the 5’-terminus, 3’- terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0847] In some embodiments, the conjugate comprises Glb-ser(Man-C5)-Man (e.g., at the 5’- terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0848] In some embodiments, the conjugate comprises Glb-ser(C6)-Man (e.g., at the 5’- terminus, 35-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0849] In some embodiments, the conjugate comprises Glb-PhC(S)NH2-Man (e.g., at the 5’- terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0850] In some embodiments, the conjugate comprises Glb-Tris-3 SulfoGai (e.g., at the 5’- iermmus, 3’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0851] In some embodiments, the conjugate comprises Glb-ser(C12)-Man (e.g., at the 5’- terminus, 3’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0852] In some embodiments, the conjugate comprises GIb-Gal-C5 (e.g., at the 5’-terminus, d’terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0853] In some embodiments, the conjugate comprises G1b-ser(Man-PEG3)-Man (e g., at the 5’- terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0854] In some embodiments, the conjugate comprises Glb-3NMC(TZ-C5) (e.g., at the 5’- terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0855] In some embodiments, the conjugate comprises Glb-Man-C15 (e.g., at the 5 ’-terminus, 3’-tenninus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand))

[0856] In some embodiments, the conjugate comprises Glb-MartPEG4 (e.g., at the 5’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0857] In some embodiments, the conjugate comprises G1 b-lysine-C 15-2NMC (e.g., at the 5’- terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0858] In some embodiments, the conjugate comprises [Glb-Man-C5][Glb-Man-C5][Glb-Man- C5][Glb-Man-C5] (e.g., at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0859] In some embodiments, the conjugate comprises [G1b-ser-Man][Glb-ser-Man][Glb-ser- Man][Glb-ser-Man] (e.g., at the 5’-terminus, 3’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0860] In some embodiments, the conjugate comprises [Glb-ser(Man-C5)-Man][Glb-ser(Man- C5)-Man][Glb-ser(Man-C5)-Man][Glb-ser(Man-C5)-Man] (e.g., at the 5’-terminus, 3’- terminus, or an internal position of the Nucleic .Acid Agent (e.g., sense and / or antisense strand)).

[0861] In some embodiments, the conjugate comprises [Glb-ser(C6)-Man][Glb-ser(C6)- Man][Gl b-ser(C6)-Man][Glb-ser(C6)-Man] (e.g., at the 5’-terminus, 3 '-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0862] In some embodiments, the conjugate comprises [Glb-PhC(S)NH2-Man][G1b-PhC(S)NH2-Man][Glb-PhC(S)NH2-Man][Glb-PhC(S)NH2-Man] (e.g., at the S’-termmus, 3’- terminus, or an internal position of the Nucleic Acid Agent (e.g , sense and / or antisense strand)).

[0863] In some embodiments, the conjugate comprises [Glb-Man-C5][Glb-Man-C5][Glb-Man- C5][Glb-Man-C5][Glb-Man-C5][Glb-Man-C5] (e.g., at the 5’-terrainus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0864] In some embodiments, the conjugate comprises [Glb-PhC(S)NH2-Man][Glb- PhC(S)NH2-Man][Glb-PhC(S)NH2-Man][Glb-PhC(S)NH2-Man][Gl b~PhC(S)NH2- Man][Glb-PhC(S)NH2-Man] (e.g., at the 5’-terminus, 3’-terminus, or an internal position of the Nucleic Acid .Agent (e.g., sense and / or antisense strand)).

[0865] In some embodiments, the conjugate comprises (Glb-ser(C12)-Man][Glb-ser(C12)- Man][Glb-ser(Cl2)-Man][Glb-ser(C12)-Man] (e.g., at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0866] In some embodiments, the conjugate comprises [Glb-ser(Man-PEG3)-Man][Glb- ser(Man-PEG3)-Man][Glb-ser(Man-PEG3)-Man][Glb-ser(Man-PEG3)-Man] (e.g., at the 5’- terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0867] In some embodiments, the conjugate comprises [Glb-Gal-C5][Glb-Gal-C5][Glb-Gal- C5][Glb-Gai-C5] (e.g., at the 5’-terminus, 3’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0868] In some embodiments, the conjugate comprises [G1b-Man-C15][G1b-Man-C15] (e.g., at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).

[0869] In some embodiments, the conjugate comprises [Glb-ManPEG4] [Glb-ManPEG4] (e.g., at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent, (e.g., sense and / or antisense strand)).

[0870] In some embodiments, the conjugate comprises [Glb-lysine-C15-2NMC] (e.g., at the 5’- terminus, 3’-terminus, or an internal position of the Nucleic Acid Agent (e.g., sense and / or antisense strand)).Saccharide-Based Ligand Units

[0871] A Saccharide-Based Ligand Unit can comprise a Saccharide-Based Ligand described herein, and can further comprise a Linker Unit described herein. In some embodiments, a Saccharide-Based Ligand Unit comprises a Saccharide-Based Ligand, but not a Linker Unit. In some embodiments, a Saccharide-Based Ligand Unit comprises a Saccharide-Based Ligand and a Linker Unit.

[0872] In some embodiments, the Saccharide-Based Ligand Unit corresponds to a Saccharide- Based Ligand Agent in which the 5 ’-position is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0873] In some embodiments, the Saccharide-Based Ligand Unit corresponds to a Saccharide- Based Ligand Agent in which the 3 ’-position is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent

[0874] In some embodiments, the Saccharide-Based Ligand Unit corresponds to a Saccharide- Based Ligand Agent in which the 2’ -position is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0875] In some embodiments, the Saccharide-Based Ligand Unit corresponds to a Saccharide- Based Ligand Agent in which the 5 ’-position is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid .Agent, and the 3 ’-position is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid .Agent, atthe 5’-terminus, 3’-terminus, or an internal position of the Nucleic Acid Agent.

[0876] In some embodiments, the Saccharide-Based Ligand Unit corresponds to a Saccharide- Based Ligand Agent in which the 5 ’-position is attached to a Ligand, a Linker Unit, and / or a Nucleic .Acid Agent, at the 5’ -terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent, and the 2’-position is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0877] In some embodiments, the Ligand is a Saccharide-Based Ligand.

[0878] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (I), (II), (III), or (IV), wherein: the 3 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent, and / or the 5 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0879] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (I), (II), (III), or (IV), wherein: the 2’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent; and / or the 5 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent

[0880] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (P), (II’), (IIP), or (IV’), wherein: the 3’-position of the Saccharide-Based Ligand Unit is atached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent; and / or the 5’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5’-termmus, 3’-terminus, or an internal position of the Nucleic Acid Agent.

[0881] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (I’), (IP), (III’), or (IV’), wherein: the 2’-position of the Saccharide-Based Ligand Unit is atached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5’-terminus, 3’-terminus, or an internal position of the Nucleic Acid Agent; and / or the 5 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5’-tenninus, 3’-terminus, or an internal position of the Nucleic Acid Agent.

[0882] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (LA), (ILA), (III- A), or (IV-A), wherein: the 3 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5’-tenninus, 3’-terminus, or an internal position of the Nucleic .Acid Agent; and / or the S’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0883] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (LA), (II- A), (III- A), or (IV-A), wherein: the 2’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent, and / or the 5 ’-position of the Saccharide-Based Ligand Unit is atached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0884] In some embodiments, at least one nucleotide in the Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (I’-A), (II’-A), (IB’-A), or (I V’ -A), wherein: the 3 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent, and / or the 5 ’-position of the Saccharide-Based Ligand Unit is atached to a Ligand, a LinkerUnit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of theNucleic Acid Agent.

[0885] Ln some embodiments, at least one nucleotide in the Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (I’-A), (IT -A), ( II I’ - A ), or (IV’-A), wherein : the 2’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5’-tenninus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent, and / or the 5 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0886] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (I-B), (II-B), (III-B), or (IV-B), wherein: the 3 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent, and / or the 5’-position of the Saccharide-Based Ligand Unit is atached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid .Agent.

[0887] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (I-B), (II-B), (III-B ), or (IV-B), wherein: the 2’-position of the Saccharide-Based Ligand Unit is atached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent; and / or the 5 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0888] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (I’-B), (II’-B), (III’-B), or j l\" -B), wherein:the 3’-position of the Saccharide-Based Ligand Unit is atached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent, and / or the 5 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5’ -terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0889] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (I’-B), (H’-B), (III’-B), or (IV’-B), wherein: the 2’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent; and / or the 5’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5’-terminus, 3’-terminus, or an internal position of the Nucleic Acid Agent

[0890] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (I-C), (II-C), (III-C), (IV-C), (V-C), (VI-C), (VII- C), or (VI II-C), wherein: the 3 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent; and / or the S’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent

[0891] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (I-C), (II-C), (III-C), (IV-C), (V-C), (VI-C), (VII- C), or (VI II-C), wherein: the 2’-position of the Saccharide-Based Ligand Unit is atached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent; and / orthe 5’-position of the Saccharide-Based Ligand Unit is atached to a Ligand, a LinkerUnit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0892] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (I’-C), (II’-C), (ni’-C), (IV’-C), (V’-C), (VI’-C), (VII’-C), or (VIII’-C), wherein: the 3 ’-position of the Saccharide-Based Ligand Unit is atached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent; and / or the 5 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0893] In some embodiments, at least one Saccharide-Based Ligand Unit corresponds to a Saccharide-Based Ligand Agent of Formula (I’-C), (II’-C), (III’-C), (IV’-C), (V’-C), (VI’-C), (VII’-C), or (VIII’-C), wherein: the 2’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent; and / or the 5 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0894] In some embodiments, at least one Saccharide-Based Ligand Unit is selected from Table C, wherein: the 3 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent; and / or the 5 ’-position of the Saccharide-Based Ligand Unit is atached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0895] In some embodiments, at least one Saccharide-Based Ligand Unit is selected from Table C, wherein:the 2’-position of the Saccharide-Based Ligand Unit is atached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent, and / or the 5 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5’ -terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.

[0896] In some embodiments, at least one Saccharide-Based Ligand Unit is selected from Table D, wherein: the 3 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent; and / or the 5’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5’-terminus, 3’-terminus, or an internal position of the Nucleic Acid Agent

[0897] In some embodiments, at least one Saccharide-Based Ligand Unit is selected from Table D, wherein: the 2’-position of the Saccharide-Based Ligand Unit is atached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid .Agent; and / or the 5 ’-position of the Saccharide-Based Ligand Unit is attached to a Ligand, a Linker Unit, and / or a Nucleic Acid Agent, at the 5 ’-terminus, 3 ’-terminus, or an internal position of the Nucleic Acid Agent.Linker Units

[0898] As used herein, a “Linker Unit” or “linker unit” refers to a moiety with an attachment to a Saccharide-Based Ligand Unit, a Saccharide-Based Ligand, and / or a Nucleic .Acid Agent.

[0899] In some embodiments, the Linker Unit has an attachment to a Saccharide-Based Ligand Unit and a Ligand.

[0900] In some embodiments, the Linker Unit has an attachment to a Saccharide-Based Ligand and a Nucleic Acid Agent.

[0901] In some embodiments, the Linker Unit has an attachment to a Saccharide-Based LigandUnit and a Nucleic Acid Agent.

[0902] In some embodiments, the Linker Unit is a ribose derivative.

[0903] Ln some embodiments, the Linker Unit is a 1 ’-alkyl modified ribose derivative, e.g., as described in PCT .Application No. PCT / US2022 / 039517 (incorporated herein by reference).

[0904] In some embodiments, the Linker Unit is a 2’-alkyl or 3’-alkyl modified ribose derivative, e.g., as described in PCT Application No. PCT / US2022 / 044377 (incorporated herein by reference).

[0905] In some embodiments, the Linker Unit is a polyhydroxylated cyclopentane derivative, e.g., as described in PCT Application No. PCT / US2022 / 045748 (incorporated herein by reference).Nucleic Acid Agents

[0906] In some embodiments, the Nucleic Acid .Agent comprises an oligonucleotide.

[0907] In some embodiments, the Nucleic Acid Agent (e.g., the oligonucleotide) comprises one or more phosphate groups or one or more analogs of a phosphate group.

[0908] In some embodiments, the Linker Unit is attached to the Nucleic Acid Agent (e.g., the oligonucleotide) via a phosphate group, or an analog of a phosphate group, in the Nucleic Acid Agent.

[0909] In some embodiments, the oligonucleotide has a length of from 1 to 40 nucleotides, from 10 to 40 nucleotides, from 12 to 35 nucleotides, from 15 to 30 nucleotides, from 18 to 25 nucleotides, or from 20 to 23 nucleotides. In some embodiments, the oligonucleotide has a length of 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides. In some embodiments, the oligonucleotide has a length of 20, 21, 22, or 23 nucleotides

[0910] In some embodiments, the Nucleic Acid Agent comprises an RNA, a DNA, or a mixture thereof.

[0911] In some embodiments, the Nucleic Acid Agent comprises an RNA.

[0912] In some embodiments, the oligonucleotide is an siRNA (e.g., a single strand siRNA (e.g., a hairpin single strand siRNA) or a double strand siRNA), microRNA, antimicroRNA, mi croRNA mimic, antagomir, dsRNA, ssRNA, aptamer, immune stimulatory' oligonucleotide, decoy oligonucleotide, splice altering oligonucleotide, triplex forming oligonucleotide, G- quadruplexe, or antisense oligonucleotide

[0913] In some embodiments, the Nucleic Acid Agent comprises a double stranded RNA (dsRNA), wherein the double stranded RNA comprises a sense strand and an antisense strand, as described herein.

[0914] In some embodiments, the Nucleic Acid .Agent comprises a double stranded siRNA (ds- siRNA), wherein the double stranded siRNA comprises a sense strand and an antisense strand, as described herein.

[0915] It is understood that sense strand is also known as passenger strand, and the terms “sense strand” and “passenger strand” are used interchangeably herein.

[0916] It is understood that antisense strand is also known as guide strand, and the terms “’antisense strand” and “guide strand” are used interchangeably herein.

[0917] In some embodiments, the oligonucleotide is an iRNA.

[0918] The term “iRNA” refers to an RNA agent which can down regulate the expression of a target gene (e.g., an siRNA), e.g., an endogenous or pathogen target RNA. While not wishing to be bound by theory, an iRNA may act by one or more of a number of mechanisms, including post-transcriptional cleavage of a target mRN A (referred to in the art as RNAi), or pre- transcriptional or pre-translational mechanisms. An iRNA can include a single strand or can include more than one strands, e.g , it can be a double stranded iRNA If the iRNA is a single strand it can include a 5' modification which includes one or more phosphate groups or one or more analogs of a phosphate group. In some embodiments, the iRNA is double stranded. In some embodiments, one or both strands of the double stranded iRNA can be modified, e.g., 5' modification.

[0919] The iRNA typically includes a region of sufficient homology to the target gene, and is of sufficient length in terms of nucleotides, such that the iRNA, or a fragment thereof, can mediate down regulation of the target gene. The iRNA is or includes a region which is at least partially, and in some embodiments fully, complementary' to the target RNA. It is not necessary- that there be perfect complementarity between the iRNA and the target, but the correspondence may be sufficient to enable the iRNA, or a cleavage product thereof, to direct sequence specific silencing, e.g , by RNAi cleavage of the target RNA, e.g , mRN A.

[0920] The nucleotides in the iRNA may be modified (e.g., one or more nucleotides may include a 2'-F or 2'-OCH3 group, or be nucleotide surrogates). The single stranded or double stranded regions of an iRNA may be modified or include nucleotide surrogates, e g., the impaired regionor regions of a hairpin structure, e.g., a region which Sinks two complementary regions, can have modifications or nucleotide surrogates. Modification to stabilize one or more 3'- or 5 '-terminus of an iRNA, e.g., against exonucleases. Modifications can include C3 (or C6, C7, Cl 2) amino linkers, thiol linkers, carboxyl linkers, non-nucleotidic spacers (C3, C6, C9, C l 2, abasic, triethylene glycol, hexaethylene glycol), special biotin or fluorescein reagents that come as phosphorami dites and that have another DMT-protected hydroxyl group, allowing multiple couplings during RNA synthesis. Modifications can also include, e.g., the use of modifications at the 2' OH group of the ribose sugar, e.g., the use of deoxyribonucleotides, e.g., deoxythymidine, instead of ribonucleotides, and modifications in the phosphate group, e.g., phosphothioate modifications. In some embodiments, the different strands will include different modifications.

[0921] In some embodiments, the strands are chosen such that the iRNA includes a single strand or unpaired region at one or both ends of the molecule. A double stranded iRNA may have an overhang, e.g., one or two 5' or 3' overhangs (e.g., at least a 3' overhang of 2-3 nucleotides). In some embodiments, the iRNA has overhangs, e.g , 3' overhangs, of 1 , 2, or 3 nucleotides in length at each end. The overhangs can be the result of one strand being longer than the other, or the result of two strands of the same length being staggered.

[0922] In some embodiments, the duplexed regions between the strands of the iRN A are between 6 and 30 nucleotides in length. In some embodiments, the duplexed regions are between 15 and 30, most preferably 18, 19, 20, 21, 22, and 23 nucleotides in length. In some embodiments, the duplexed regions are between 6 and 20 nucleotides, most preferably 6, 7, 8, 9, 10, 1 1 and 12 nucleotides in length.

[0923] The oligonucleotide may be that described in U.S. Patent Publication Nos. 2009 / 0239814, 2012 / 0136042, 2013 / 0158824, or 2009 / 0247608, each of which is hereby incorporated by reference.

[0924] In some embodiments, the oligonucleotide is an siRNA.

[0925] In some embodiments, the oligonucleotide is a single strand siRN A

[0926] In some embodiments, the oligonucleotide is a double strand siRNA, for example, double strand siRNA described herein.

[0927] A “single strand siRNA” as used herein, is an siRNA which is made up of a single strand, which includes a duplexed region, formed by intra-strand pairing, e g., it may be, or include, a hairpin or pan-handle structure. Single strand siRNAs may be antisense with regard to the targetmolecule

[0928] A single strand siRNA may be sufficiently long that it can enter the RISC and participate in RISC mediated cleavage of a target mRNA. A single strand siRNA is at least 14, and in some embodiments at least 15, 20, 25, 29, 35, 40, or 50 nucleotides in length. In some embodiments, it is less than 200, 100, 80, 60, 50, 40, or 30 nucleotides in length,

[0929] In some embodiments, the single strand siRNA has a length of from 10 to 40 nucleotides, from 12 to 35 nucleotides, from 15 to 30 nucleotides, from 18 to 25 nucleotides, or from 20 to 23 nucleotides. In some embodiments, the single strand siRNA has a length of 18, 19, 20, 21, 22,23, 24, or 25 nucleotides. In some embodiments, the single strand siRNA has a length of 20, 21,22, or 23 nucleotides.

[0930] Hairpin siRNAs may have a duplex region equal to or at least 17, 18, 19, 20, 21, 22, 23,24, or 25 nucleotide pairs. The duplex region may be equal to or less than 200, 100, or 50 nucleotide pairs in length. In some embodiments, ranges for the duplex region are 15-30, 17 to23, 19 to 23, and 19 to 21 nucleotides pairs in length. The hairpin may have a single strand overhang or terminal unpaired region. In some embodiments, the overhangs are 2-3 nucleotides in length. In some embodiments, the overhang is at the sense side of the hairpin and in some embodiments on the antisense side of the hairpin.

[0931] In some embodiments, the oligonucleotide is a double strand siRNA.

[0932] A “double stranded siRNA” as used herein, is an siRNA which includes more than one, and in some cases two, strands in which interchain hybridization can form a region of duplex structure.

[0933] In some embodiments, the sense strand of a double stranded siRNA may be equal to or at least 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 29, 40, or 60 nucleotides in length It may be equal to or less than 200, 100, or 50 nucleotides in length. Ranges may be 17 to 25, 19 to 23, 19 to 21, 21 to 23, or 20 to 22 nucleotides in length.

[0934] In some embodiments, the sense strand has a length of from 10 to 40 nucleotides, from 12 to 35 nucleotides, from 15 to 30 nucleotides, from 18 to 25 nucleotides, or from 20 to 23 nucleotides. In some embodiments, the sense strand has a length of 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides. In some embodiments, the sense strand has a length of 20, 21, 22, or 23 nucleotides.

[0935] In some embodiments, the sense strand has a length of 18, 19, 20, 21, or 22 nucleotides.

[0936] In some embodiments, the antisense strand of a double stranded siRNA may be equal to or at least, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 29, 40, or 60 nucleotides in length. It may be equal to or less than 200, 100, or 50 nucleotides in length. Ranges may be 17 to 25, 19 to 23, 19 to 21, 21 to 23, or 20 to 22 nucleotides in length.

[0937] In some embodiments, the antisense strand has a length of from 10 to 40 nucleotides, from 12 to 35 nucleotides, from 15 to 30 nucleotides, from 18 to 25 nucleotides, or from 20 to 23 nucleotides In some embodiments, the antisense strand has a length of 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides. In some embodiments, the antisense strand has a length of 20, 21, 22, or 23 nucleotides.

[0938] In some embodiments, the antisense strand has a length of 20, 21, 22, 23, or 24 nucleotides.

[0939] In some embodiments, the sense strand has a length of 18, 19, 20, 21, or 22 nucleotides, and the antisense strand has a length of 20, 21, 22, 23, or 24 nucleotides.

[0940] In some embodiments, the sense strand has a length of 18 nucleotides, and the antisense strand has a length of 20 nucleotides.

[0941] In some embodiments, the sense strand has a length of 19 nucleotides, and the antisense strand has a length of 21 nucleotides.

[0942] In some embodiments, the sense strand has a length of 20 nucleotides, and the antisense strand has a length of 22 nucleotides.

[0943] In some embodiments, the sense strand has a length of 21 nucleotides, and the antisense strand has a length of 23 nucleotides.

[0944] In some embodiments, the sense strand has a length of 22 nucleotides, and the antisense strand has a length of 24 nucleotides.

[0945] The double strand portion of a double stranded siRNA may be equal to or at least, 14, 15, 16 17, 18, 19, 20, 21, 22, 23, 24, 25, 29, 40, or 60 nucleotide pairs in length. It may be equal to or less than 200, 100, or 50 nucleotides pairs in length. Ranges may be 15 to 30, 17 to 23, 19 to 23, and 19 to 21 nucleotides pairs in length.

[0946] In some embodiments, the siRNA is sufficiently large that it can be cleaved by an endogenous molecule, e.g., by Dicer, to produce smaller siRNAs, e.g., siRNAs agents.

[0947] The sense and antisense strands may be chosen such that the double-stranded siRNA includes a single strand or unpaired region at one or both ends of the molecule. Thus, a double-stranded siRNA may contain sense and antisense strands, paired to contain an overhang, e g., one or two 5' or 3' overhangs, or a 3' overhang of 1-3 nucleotides. The overhangs can be the result of one strand being longer than the other, or the result of two strands of the same length being staggered. Some embodiments will have at least one 3' overhang. In some embodiments, both ends of an siRNA molecule will have a 3' overhang. In some embodiments, the overhang is 2 nucleotides.

[0948] In some embodiments, the length for the duplexed region is between 15 and 30, or 18, 19, 20, 21, 22, and 23 nucleotides in length, e.g., in the ssiRNA range discussed above. ssiRNAs can resemble in length and structure the natural Dicer processed products from long dsiRNAs. Embodiments in which the two strands of the ssiRNA are attached, e.g., covalently attached are also included. Hairpin, or other single strand structures which provide the required double stranded region, and a 3' overhang are also contemplated.

[0949] The siRNAs described herein, including double-stranded siRNAs and single-stranded siRNAs can mediate silencing of a target RNA, e g., mRNA, e.g., a transcript of a gene that encodes a protein. For convenience, such mRNA is also referred to herein as mRNA to be silenced. Such a gene is also referred to as a target gene. In general, the RNA to be silenced is an endogenous gene or a pathogen gene. In addition, RNAs other than mRNA, e g., tRNAs, and viral RNAs, can also be targeted.

[0950] As used herein, the phrase “mediates RNAi” refers to the ability to silence, in a sequence specific manner, a target RNA. While not wishing to be bound by theory, it is believed that silencing uses the RNAi machinery or process and a guide RNA, e.g., an ssiRNA of 21 to 23 nucleotides.

[0951] In some embodiments, an siRNA is “sufficiently complementary'” to a target RNA, e.g., a target mRNA, such that the siRNA silences production of protein encoded by the target mRNA. In another embodiment, the siRNA is “exactly complementary'’’ to a target RNA, e.g., the target RNA and the siRNA anneal, for example to form a hybrid made exclusively of Watson-Crick base pairs in the region of exact complementarity. A “sufficiently complementary'” target RNA can include an internal region (e.g., of at least 10 nucleotides) that is exactly complementary' to a target RNA. Moreover, in some embodiments, the siRNA specifically discriminates a singlenucleotide difference. In this case, the siRNA only mediates RNAi if exact complementary is found in the region (e g., within 7 nucleotides of) the single-nucleotide difference.

[0952] MicroRNAs: Micro RNAs (miRNAs) are a highly conserved class of small RNA molecules that are transcribed from DNA in the genomes of plants and animals, but are not translated into protein. Processed miRNAs are single stranded "17-25 nucleotide (nt) RNA molecules that become incorporated into the RNA-induced silencing complex (RISC) and have been identified as key regulators of development, cell proliferation, apoptosis and differentiation. They are believed to play a role in regulation of gene expression by binding to the 3 '-untranslated region of specific mRNAs. RISC mediates down-regulation of gene expression through translational inhibition, transcript cleavage, or both. RISC is also implicated in transcriptional silencing in the nucleus of a wide range of eukaryotes.

[0953] The number of niiRNA sequences identified to date is large and growing, illustrative examples are known in the art.

[0954] Antisense Oligonucleotides: In some embodiments, a nucleic acid is an antisense oligonucleotide directed to a target polynucleotide. The term “antisense oligonucleotide” or simply “antisense” is meant to include oligonucleotides that are complementary to a targeted polynucleotide sequence. .Antisense oligonucleotides are single strands of DNA or RNA that are complementary to a chosen sequence, e.g. a target gene mRNA. Antisense oligonucleotides are thought to inhibit gene expression by binding to a complementary mRN A. Binding to the target mRNA can lead to inhibition of gene expression either by preventing translation of complementary mRNA strands by binding to it, or by leading to degradation of the target mRNA. Antisense DNA can be used to target a specific, complementary (coding or non-coding) RNA. If binding takes places this DNA / RNA hybrid can be degraded by the enzyme RNase H. In some embodiments, antisense oligonucleotides contain from about 10 to about 50 nucleotides, more preferably about 15 to about 30 nucleotides The term also encompasses antisense oligonucleotides that may not be exactly complementary to the desired target gene. Thus, instances where non-target specific-activities are found with antisense, or where an antisense sequence containing one or more mismatches with the target sequence is the most preferred for a particular use, are contemplated.

[0955] Antisense oligonucleotides have been demonstrated to be effective and targeted inhibitors of protein synthesis, and, consequently, can be used to specifically inhibit protein synthesis by a targeted gene. The efficacy of antisense oligonucleotides for inhibiting protein synthesis is well established. For example, the synthesis of polygalacturonase and the muscarine type 2acetylcholine receptor are inhibited by antisense oligonucleotides directed to their respective rnRNA sequences (U.S. Pat. Nos. 5,739,119 and 5,759,829 each of which is incorporated by reference). Further, examples of antisense inhibition have been demonstrated with the nuclear protein cyclin, the multiple drug resistance gene (MDG1), ICAM- 1, E-selectin, STK-1, striatal GABAA receptor and human EGF, which are known in the art. Furthermore, antisense constructs have also been described that inhibit and can be used to treat a variety of abnormal cellular proliferations, e.g. cancer, which are known in the art.

[0956] Methods of producing antisense oligonucleotides are known in the art and can be readily adapted to produce an antisense oligonucleotide that targets any polynucleotide sequence. Selection of antisense oligonucleotide sequences specific for a given target sequence is based upon analysis of the chosen target sequence and determination of secondary structure, Tm, binding energy, and relative stability. Antisense oligonucleotides may be selected based upon their relative inability to form dimers, hairpins, or other secondary' structures that would reduce or prohibit specific binding to the target mRNA in a host cell. Highly preferred target regions of the mRNA include those regions at or near the AUG translation initiation codon and those sequences that are substantially complementary to 5' regions of the mRNA. These secondary structure analyses and target site selection considerations can be performed, for example, using v.4 of the OLIGO primer analysis software (Molecular Biology Insights) and / or the BLASTN 2.0.5 algorithm software (Altschul et al., Nucleic Acids Res. 1997, 25(17):3389-402).

[0957] Antagomirs: Antagomirs are RNA-like oligonucleotides that harbor various modifications for RNAse protection and pharmacologic properties, such as enhanced tissue and cellular uptake. They differ from normal RNA by, for example, complete 2'-O-methylation of sugar, phosphorothioate backbone and, for example, a cholesterol -moiety at 3 ’-end. Antagomirs may be used to efficiently silence endogenous miRNAs by forming duplexes comprising the antagomir and endogenous miRNA, thereby preventing miRNA-induced gene silencing. An example of antagomir-mediated miRNA silencing is the silencing of miR-122, described in Krutzfeldt et al, Nature, 2005, 438: 685-689, which is expressly incorporated by reference herein in its entirety Antagomir RNAs may be synthesized using standard solid phase oligonucleotide synthesis protocols. See U.S. Patent Application Publication Nos. 2007 / 0123482 and 2007 / 0213292 (each of which is incorporated herein by reference).

[0958] An antagomir can include ligand-conjugated monomer subunits and monomers foroligonucleotide synthesis. Exemplary monomers are described in U S Patent Application Publication No. 2005 / 0107325, which is incorporated by reference in its entirety. An antagomir can have a ZXY structure, such as is described in WO 2004 / 080406, which is incorporated by reference in its entirety. An antagomir can be complexed with an amphipathic moiety. Exemplary amphipathic moieties for use with oligonucleotide agents are described in WO 2004 / 080406, which is incorporated by reference in its entirety.

[0959] Aptamers'. Aptamers are nucleic acid or peptide molecules that bind to a particular molecule of interest with high affinity and specificity. DNA or RNA aptamers have been successfully produced which bind many different entities from large proteins to small organic molecules. See, e.g., Hermann and Patel, Science 287:820-5 (2000), which is incorporated by reference in its entirety. Aptamers may be RNA or DNA based, and may include a riboswitch. A riboswitch is a part of an mRNA molecule that can directly bind a small target molecule, and whose binding of the target affects the gene's activity. Thus, an mRNA that contains a riboswitch is directly involved in regulating its own activity, depending on the presence or absence of its target molecule. Generally, aptamers are engineered through repeated rounds of in vitro selection or equivalently, SELEX (systematic evolution of ligands by exponential enrichment) to bind to various molecular targets such as small molecules, proteins, nucleic acids, and even cells, tissues and organisms. The aptamer may be prepared by any known method, including synthetic, recombinant, and purification methods, and may be used alone or in combination with other aptamers specific for the same target. Further, as described more fully herein, the term “aptamer” specifically includes “secondary aptamers” containing a consensus sequence derived from comparing two or more known aptamers to a given target.

[0960] Ribozymes: According to another embodiment, nucleic acid-lipid panicles are associated with ribozymes. Ribozymes are RNA molecules complexes having specific catalytic domains that possess endonuclease activity. For example, a large number of ribozymes accelerate phosphoester transfer reactions with a high degree of specificity, often cleaving only one of several phosphoesters in an oligonucleotide substrate. This specificity has been attributed to the requirement that the substrate bind via specific base-pairing interactions to the internal guide sequence (“IGS”) of the ribozyme prior to chemical reaction.

[0961] At least six basic varieties of naturally-occurring enzymatic RNAs are known presently. Each can catalyze the hydrolysis of RNA phosphodi ester bonds in trans (and thus can cleaveother RNA molecules) under physiological conditions. In general, enzymatic nucleic acids act by first binding to a target RNA. Such binding occurs through the target binding portion of a enzymatic nucleic acid which is held in close proximity to an enzymatic portion of the molecule that acts to cleave the target RNA. Thus, the enzymatic nucleic acid first recognizes and then binds a target RNA through complementary base-pairing, and once bound to the correct site, acts enzymatically to cut the target RNA. Strategic cleavage of such a target RN A will destroy its ability to direct synthesis of an encoded protein After an enzymatic nucleic acid has bound and cleaved its RNA target, it is released from that RNA to search for another target, and can repeatedly bind and cleave new targets.

[0962] The enzymatic nucleic acid molecule may be formed in a hammerhead, hairpin, a hepatitis 5 virus, group I intron or RNaseP RNA (in association with an RNA guide sequence) or Neurospora VS RNA motif, for example, which are known in the art Important characteristics of enzymatic nucleic acid molecules used are that they have a specific substrate binding site which is complementary to one or more of the target gene DNA or RNA regions, and that they have nucleotide sequences within or surrounding that substrate binding site which impart an RNA cleaving activity to the molecule. Thus the ribozyme constructs need not be limited to specific motifs mentioned herein.

[0963] Methods of producing a ribozyme targeted to any polynucleotide sequence are known in the art. Ribozymes may be designed as described in Ini. Pat. Appl. Publ. Nos. WO 93 / 23569 and WO 94 / 02595, each specifically incorporated herein by reference, and synthesized to be tested in vitro and in vivo, as described therein.

[0964] Ribozyme activity can be optimized by altering the length of the ribozyme binding arms or chemically synthesizing ribozymes with modifications that prevent their degradation by serum ribonucleases, modifications which enhance their efficacy in cells, and removal of stem II bases to shorten RNA synthesis times and reduce chemical requirements, which are known in the art.

[0965] Imnmnostinuilatory Oligonucleotides.' Nucleic acids associated with lipid particles may be immunostimulatory, including iinrnuiiostimulatory oligonucleotides (ISS; single- or doublestranded) capable of inducing an immune response when administered to a subject, which may be a mammal or other patient. ISS include, e.g., certain palindromes leading to hairpin secondary structures (see Yamamoto S., et al. (1992) J. Immunol. 148; 4072-4076, which is incorporated by reference in its entirety), or CpG motifs, as well as other known ISS features (such as multi-Gdomains, see WO 96 / 1 1266, which is incorporated by reference in its entirety).

[0966] The immune response may be an innate or an adaptive immune response. The immune system is divided into a more innate immune system, and acquired adaptive immune system of vertebrates, the latter of which is further divided into humoral cellular components. In some embodiments, the immune response may be mucosal.

[0967] In some embodiments, an immunostimulatory nucleic acid is only immunostimulatory' when administered in combination with a lipid particle, and is not immunostimulatory when administered in its “free form.” Such an oligonucleotide is considered to be immunostimulatory'.

[0968] Immunostimulatory' nucleic acids are considered to be non-sequence specific when it is not required that they specifically bind to and reduce the expression of a target polynucleotide in order to provoke an immune response. Thus, certain immunostimulatory nucleic acids may comprise a sequence corresponding to a region ...

Claims

1. CLAIMS1. .4 Saccharide-Based Ligand of Formula (A):wherein:E is O or S;ml is an integer ranging from 0 to about 100; each pl is independently an integer ranging from 0 to about 100;W is a bond or C(Rw)(3-q); q is 1, 2, or 3; each R'' is independently H, halogen, or C1-C6alkyl optionally substituted with one or more halogen; each SA is independently a saccharide moiety, and indicates the point of attachment to the rest of a Saccharide-Based Ligand Agent, Saccharide-Based Ligand Scaffold, Saccharide-Based Ligand Unit, or conjugate.

2. A Saccharide-Based Ligand Scaffold being a compound of Formula (AA):or a pharmaceutically acceptable salt thereof, wherein: C2-C6each RL1is independently H or C1-C6, alkyl optionally substituted with one or more halogen; m l is an integer ranging from 0 to about 100; each pl is independently an integer ranging from 0 to about 100,W is a bond or C(Rvv)(3-q); q is I, 2, or 3;each R'* is independently H, halogen, or C1-C6alkyl optionally substituted with one or more halogen; and each SA is independently a saccharide moiety.

3. A conjugate or a pharmaceutically acceptable salt thereof, comprising:(i) one or more Nucleic Acid Agent; and(ii) one or more Saccharide-Based Ligand, each independently being L of Formula (A):wherein :indicates the point of attachment to the rest of the conjugate.

4. The Saccharide-Based Ligand of claim 1, wherein indicates the rest of a Saccharide-Based Ligand Agent.

5. The Saccharide-Based Ligand of claim 1, whereinindicates the point of attachment to the rest of a Saccharide-Based Ligand Scaffold.

6. I he Saccharide-Based Ligand of claim 1, wherein indicates the point of attachmentto the rest of a Saccharide-Based Ligand Unit.

7. The Saccharide-Based Ligand of claim 1 , whereinindicates the point of attachment to the rest of a conjugate.

8. The Saccharide-Based Ligand Scaffold of claim 2, wherein REis -OR1'1.

9. The Saccharide-Based Ligand Scaffold of claim 8, wherein R*'1is H.

10. The Saccharide-Based Ligand Scaffold of claim 8, wherein REiis -C(=O)-(C1-C6alkyl),Cf-Ce alkyl, C2-C6alkenyl, C2-C6alkynyl, or a hydroxy protecting group, wherein the -C(=O)-(C1-C6alkyl), C1-C6 alkyl, C2-C6alkenyl, or C2-C6alkynyl is optionally substituted with one or more halogen.11 . The Saccharide-Based Ligand Scaffold of claim 2, wherein Rfis -N(RE2)?..

12. The Saccharide-Based Ligand Scaffold of claim 11, wherein at least one RE2is H.

13. The Saccharide-Based Ligand Scaffold of claim 11, wherein at least one RE2is -C(=O)~(C1-C6 alkyl), C1-C6alkyl, Ci-Ce alkenyl, C2-C6alkynyl, or an amino protecting group, wherein the -C(=O)-(C1-C6alkyl), C a1-lCk6yl, C2-C6alkenyl, or C2-C0 alkynyl is optionally substituted with one or more halogen.

14. The Saccharide-Based Ligand Scaffold of claim 2, wherein RLis -C(RE3)3.

15. The Saccharide-Based Ligand Scaffold of claim 14, wherein at least one RE3is H.

16. The Saccharide-Based Ligand Scaffold of claim 14, wherein at least one RE3is halogen, -C(=O)-(C1-C6alkyl), C1-C6alkyl, C2-C6alkenyl, or C2-C6alkynyl, wherein the -C(=O)-(C1-C6alkyl), C1-C6alkyl, C2-C6alkenyl, or C2-C6alkynyl is optionally substituted with one or more halogen.

17. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of anyone of claims 1-16, wherein E is 018. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of any one of claims 1-16, wherein E is S19. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of any one of claims 1 -18, wherein at least one L1is C1-C12 alkylene, Cs-Cio arylene, 5- to 10- membered, -O-, or -NR1wherein the C1-C12 alkylene is optionally substituted with one or more oxo, cyano, halogen, -ORLl, -N(RL1)2, -N(RL1)-C(=O)-(Ci-Ci2 alkyl), -N(Ru)-C(=O)-(Ci- C12 haloalkyl), C?-Cs cycloalkyl, 3- to 8-membered heterocycloalkyl, Cs-Cio aryl, or 5- to 10- membered heteroaryl, and wherein the Cs-Cso arylene or 5- to 10-membered heteroarylene is optionally substituted with one or more halogen, C1-C12 alkyl, or C1-C12 haloalkyl.

20. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of any one of claims 1-19, wherein ml is an integer ranging from 0 to about 30.21 . The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of any one of claims 1-20, wherein each pl is independently an integer ranging from 0 to about 30.

22. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of any one of claims 1-21, wherein q is 1, and W is a bond or C(RW)?23. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of any one of claims 1-21, wherein q is 2, and W is C(RW).24 The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of any one of claims 1-21, wherein q is 3, and W is C.

25. The Saccharide-Based Ligand Scaffold of claim 2, wherein the Saccharide-Based Ligand Scaffold is a compound of Formula(AA-1) or a pharmaceutically acceptable salt thereof, wherein: each L2is independentlyCi2 alkylene, C6-C10 arylene, 5- to 10-membered heteroarylene, -O-, or -NH-, wherein the C1-C6? alkylene is optionally substituted with one or more halogen, -OH, -NHz, -NH~C(=O)-(Ci-Ci2 alkyl), or -NH-C(=O)-(Ci-Ci2 haloalkyl), and wherein the C6-C10 arylene or 5- to 10-membered heteroarylene is optionally substituted with one or more halogen, Ci-Cn alkyl, or C1-C12 haloalkyl; m2 is an integer ranging from 0 to about 50; and each p2 is independently an integer ranging from 0 to about 50.

26. The Saccharide-Based Ligand or conjugate of claim 1 or claim 3, wherein theSaccharide-Based Ligand is of Formula (A-l):wherein:each L2is independently -CH2CH2O-, ---OCH2CH2-, -C(=O)-NH- -NH-C(=O)-, Ci- C12 alkylene, Ce-Cio arylene, 5- to 10-membered heteroarylene,or -NH-, wherein the C1-C12 alkylene is optionally substituted with one or more halogen, -OH, -NH2, -NH-C(=0)-(Ci-Ci2 alkyl), or -NH-C(=O)-(C]-Ci2 haloalkyl), and wherein the Cs-Cio arylene or 5- to 10-membered heteroarylene is optionally substituted with one or more halogen, C1-C12 alkyl, or C1-C12 haloalkyl; m2 is an integer ranging from 0 to about 50; and each p2 is independently an integer ranging from 0 to about 50.

27. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of claim25 or claim 26, wherein at least one L2is --CH2CH2O---,C(=O)---, or C1-C12 alkylene optionally substituted with one or more halogen, -OH, -NH2, -NH- C(-O)-(C1-Ci2 alkyl), or -Xi LC( O)-((V( 2 haloalkyl).

28. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of claim 25 or claim 26, wherein at least one L2is phenylene or triazolylene29. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of any one of claims 25-28, wherein m2 is an integer ranging from 0 to about 30.

30. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of anyone of claims 25-29, wherein each p2 is independently an integer ranging from 0 to about 30.

31. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of any one of claims 1-30, wherein at least one saccharide moiety is a monosaccharide moiety.

32. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of anyone of claims 1-30, wherein at least one saccharide moiety is a polysaccharide moiety.

33. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of any one of claims 1-32, wherein at least one saccharide moiety is of Formula (B):wherein each ofR”, R2’, R3’, R4’, and R5’ is independently H, halogen, C1-C6alkyl optionally substituted with one or more halogen, -ORa, oreach Ra’ is independently, H, C1-C6. alkyl optionally substituted with one or more halogen, -each of R’3, R2a, R3a, R4a, and R5ais independently « *, H, halogen, C1-C6 alkyl optionally substituted with one or more halogen, -OH, -SChH, -OSO3H, or , alkoxy C1-C6optionally substituted with one or more halogen, whereinindicates the point of attachment to the rest of Formula (B), and wherein oneis present for eachwhereinindicates the point of attachment to the rest of L, and wherein oneis present in Formula (B).

34. The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of claim33, wherein at least one saccharide moiety is of Formula (B-I), (B-2), (B-3), or (B-4):35 The Saccharide-Based Ligand, Saccharide-Based Ligand Scaffold, or conjugate of anyone of claims 1-3-4, whereinis selected from the structures of Table X.

36. The Saccharide-Based Ligand Scaffold of claim 2, wherein the Saccharide-Based Ligand Scaffold is selected from the compounds of Table Y or a compound in Table Y, wherein one or more the moi eties in the compound are protected with a protection group, or a pharmaceutical ly acceptable salt thereof.

37. The conjugate of any one of claims 3, 17-24, and 26-35, wherein the conjugate comprises one or more Saccharide-Based Ligand Unit, wherein each Saccharide-Based Ligand Unit independently is:wherein:B is H, C1-C6 alkyl, or a nucleobase moiety;V is -O-, -NRV-, or -C(RV>;each R' independently is H or C1-C6alkyl optionally substituted with one or more halogen;X is H, halogen, or -ORX;RAis H, C1-C6 alkyl, or -(Ci-Cc, alkyl)-(Cb-Cio aryl), wherein the C1-C6alkyl or -(C1-C6alkyl)-(C6~Cio aiyl) is optionally substituted with one or more RXa; or Rxand R4together form C1-C6alkylene; each RXaindependently is halogen, Ci-Cs alkyl, or -O-(C1-C6alkyl), wherein the C1-C6alkyl or -O-(C1-C6alkyl) is optionally substituted with one or more halogen; each R5independently is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen; or two vicinal Rlform a bond;R1is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen;R2is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen;R* is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen,R4is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen; or R4and Rxtogether form C1-C6alkylene; each R5independently is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen; and n is an integer ranging from 0 to about 10; and when the Saccharide-Based Ligand Unit is attached to the 3 ’-terminus of the Nucleic Acid Agent,each of # and ## independently is an attachment to the rest of the conjugate38. The conjugate of any one of claims 3, 17-24, 26-35, and 37, wherein the Nucleic AcidAeent comprises an oligonucleotide.

39. A conjugate selected from the conjugates of Table F, and pharmaceutically acceptable salts thereof.

40. A pharmaceutical composition comprising the conjugate of any one of claims 3, 17-24, 26-35, and 37-39, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

41. A method of (i) modulating the expression of a target gene in a subject, (ii) delivering a Nucleic Acid Agent to a subject, or (iii) treating or preventing a disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the conjugate of any one of claims 3, 17-24, 26-35, and 37-39, or a pharmaceutically acceptable salt thereof.

42. The conjugate of any one of claims 3, 17-24, 26-35, and 37-39, or a pharmaceutically acceptable salt thereof, for (i) modulating the expression of a target gene in a subject, (ii) delivering a Nucleic Acid Agent to a subject, or (iii) treating or preventing a disease in a subject in need thereof.

43. Use of the conjugate of any one of claims 3, 17-24, 26-35, and 37-39, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for (i) modulating the expression of a target gene in a subject, (ii) delivering a Nucleic Acid Agent to a subject, or (iii) treating or preventing a disease in a subject in need thereof.

44. The method, conjugate, or use of any one of claims 41-43, wherein the subject is a human.

45. A compound of Formulaor a pharmaceutically acceptable salt thereof, wherein:L comprises at least one saccharide moiety;B is H, C1-C6alkyl, or a nucleobase moiety;V is -O-, -NR?-, or -C(RV)2-; each Rvindependently is H or aClk1y-Cl6optionally substituted with one or more halogen;X is H, halogen, or -ORX;Rxis H, C1-C6alkyl, or -(C1-C6alkyll-fCe-Cio aryl), wherein the C1-C6alkyl or -(C1-C6alkyl)-(Ce-Cio aryl) is optionally substituted with one or more RAa; or Rxand R4together form Ci-C-6 alkylene; each RXaindependently is halogen, Ci-C« alkyl, or -O-(C1-C6alkyl), wherein the Ci-C« alkyl or -O-(C1-C6alkyl) is optionally substituted with one or more halogen;Y is H, C1-C6alkyl optionally substituted with one or more halogen, -P(RV)2, -or a hydroxy protecting group, each R ‘ independently is H or C1-C6alkyl optionally substituted with one or more halogen or cyano;Z is H, C1-C6alkyl optionally substituted with one or more halogen, -P(RZ)2, - P(ORZ)(N(RZ)2), ~P(-O)(ORZ)RZ, -P(-S)(ORZ)RZ, -P(-O)(SRZ)RZ, ~P(-S)(SRZ)RZ, - P(=O)(ORZ)2, -P(=S)(ORZ)2, -P(=O)(SRZ)2, -P(=S)(SRZ)2, or a hydroxy protecting group; each Rzindependently is H or C1-C6alkyl optionally substituted with one or more halogen or cyano; or Y and Z in Formula (I) or (III), together form -Si(RL’)2-O-Si(RL")2~, wherein each R1’ independently is H or C1-C6alkyl; each Raindependently is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen; or two vicinal Raform a bond;R1is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen;R2is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen;R3is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen,R4is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen; or R4and Rxtogether form C1-C6, alkylene; each R5independently is H, halogen, or C1-C6alkyl optionally substituted with one or more halogen; and n is an integer ranging from 0 to about 10.

46. The compound of claim 45, wherein the compound is selected from the compounds of Table L, or a pharmaceutically acceptable salt thereof.

Images