Carbohydrate conjugates as delivery agents for oligonucleotides

A ligand-containing conjugate having the structure shown in formula (I):

• wherein:
• A and B are each independently for each occurrence O, N(RN), or S;
• one of X and Y is a solid support, optionally linked via a linker group, or a phosphoramidite, and the other of X and Y is a protecting group;
• R is L1 or has the structure shown in formula (II)-(V)
• q2A, q2B, q3A, q3B, q4A, q4B, q5A, q5B and q5C represent independently for each occurrence 0-20 and wherein the repeating unit can be the same or different;
• Q is absent, -(P7-Q7-R7)p-T7- , or -T7-Q7-TT-B′-T8′-Q8-T8-;
• P2A, P2B, P3A, P3B, P4A, P4B, P5A, P5B, P5C, P7, T2A, T2B, T3A, T3B, T4A, T4B, T5A, T5B, T5C, T7, T7′, T8 and T8′ are each independently for each occurrence absent, CO, NH, O, S, OC(O), C(O)O, NHC(O), C(O)NH, CH2, CH2NH, NHCH2, OCH2 or CH2O;
• B′ is —CH2—N(BL)—CH2—;
• BL is -TB-QB-TB′-Rx;
• Q2A, Q2B, Q3A, Q3B, Q4A, Q4B, Q5A, Q5B, Q5C, Q7, Q8 and QB are independently for each occurrence absent, alkylene, substituted alkylene and wherein one or more methylenes can be interrupted or terminated by one or more of O, S, S(O), SO2, N(RN), C(R′)═C(R′), C≡C or C(O);
• TB and TB′ are each independently for each occurrence absent, CO, NH, O, S, OC(O), C(O)O, NHC(O), C(O)NH, NHC(O)NH, NHC(O)O, OC(O)NH, CH2, CH2NH, NHCH2, OCH2, or CH2O;
• Rx is a lipophile, or a cationic lipid;
• R2A, R2B, R3A, R3B, R4A, R4B, R5A, R5B, R5c, and R7 are each independently for each occurrence absent, NH, O, S, CH2, C(O)O, OC(O), C(O)NH, NHC(O), NHCH(Ra)C(O), C(O)—CH(Ra)—NH, CO, CH═N—O
• or heterocyclyl;
• L1, L2A, L2B, L3A, L3B, L4A, L4B, L5A, L5B and L5C are each independently for each occurrence a carbohydrate or a derivative thereof having hydroxyl protecting group(s);
• R′ and R″ are each independently H, C1-C6 alkyl, OH, SH, or N(RN)2;
• RN is independently for each occurrence methyl, ethyl, propyl, isopropyl, butyl or benzyl;
• Ra is H or amino acid side chain;
• and
• p represents independently for each occurrence 0-20.