Targeting Lipids

A targeting lipid having a structure shown in formula (CIII)

• L110 is L112,
• R100 is independently for each occurrence absent, CO, NH, O, S, S—S, —C(CH3)2—S—S—, —CH(CH3)—S—S—, C(O), OC(O), C(O)O, NHC(O), C(O)NH, NHCH2, CH2, CH2NH, CH2O, CH═N—O, heteroaryl, heterocycle,
• A is O, NH, NCH3, S, CH2, S—S, —C(CH3)2—S—S—, —CH(CH3)—S—S—, —O—N═C—, —C(O)—N(H)—N═C—, —C═N—O—, —C═N—N(H)—C(O)—, —C(O)N(Me)-N═C—, —C═N—N(Me)-C(O)—, —O—C(O)—O—, —O—C(O)—NH—, —NH—C(O)—O—, —NH—C(O)—NH—, —N(Me)-C(O)—N(Me)-, —N(H)—C(O)—N(Me)-, —N(Me)-C(O)—N(H)—, —C(O)—O—, —C(O)—N(H)—, —C(O)—N(Me)-, —O—C(O)—, —NH—C(O)—, —N(Me)-C(O)—, —C═N—, —N═C—,
• heterocycle or heteroaryl;
• L111 is L113, L114,
• L112 is independently for each occurrence lipid, lipophile, alkyl, alkenyl or alkynyl, each of which is optionally substituted with one or more substituents;
• L113 is independently for each occurrence —CH2CH2(OCH2CH2)pO(CH2)qCH2-L114;
• L114 is independently for each occurrence a ligand, —C(O)-ligand, —O—C(O)-ligand, —N(H)-ligand, —O—C(O)—N(H)-ligand, —O—C(O)—O-ligand, —NH—C(O)—N(H)-ligand, —NH—C(O)—O-ligand, —S—S-ligand, —O—N═C-ligand, —NH—N═C-ligand, —C═N—O-ligand, —C═N—N(H)-ligand, heterocycle-ligand, heteroaryl-ligand,
• p is 1-1000;
• and
• q is 1-20.

A targeting lipid having a structure shown in formula (I)

• wherein:
• LA is a ligand chosen from a carbohydrate, glucose, mannose, galactose, N-acetyl-galactosamine, fucose, glucosamine, lactose, maltose, folate, peptide, or has the structure shown in formula II-V:
• q, q2A, q2B, q3A, q3B, q4A, q4B, q5A, q5B and q5C represent independently for each occurrence 0-20;
• p, P2A, P2B, P3A, P3B, P4A, P4B, P5A, P5B, P5C, T, T2A, T2B, T3A, T3B, T4A, T4B, T5A, T5B and T5C are each independently for each occurrence absent, NR′, O, S, C(O), OC(O), C(O)O, NHC(O), C(O)NH, NHCH2, CH2, CH2NH or CH2O, NHCH(Ra)C(O), —C(O)—CH(Ra)—NH—, CO, CH═N—O, CH2S, urea, heterocycle, heteroaryl, H
• Q, Q2A, Q2B, Q3A, Q3B, Q4A, Q4B, Q5A, Q5B and Q5C are independently for each occurrence absent, —(CH2)n—, —C(R′)(R″)(CH2)n—, —(CH2)mC(R′)(R″)—, —(CH2CH2O)pCH2CH2—, or —(CH2CH2O)pCH2CH2NH—;
• LB is selected from a group consisting of lipophile, steroid, terpene, vitamin, ceramide, or has the structure of formula (VI):
• R, R2, R2A, R2B, R3A, R3B, R4A, R4B, R5A, R5B, R5C, R6, R6A and R6B are each independently for each occurrence absent, CO, NH, NR′, O, S, C(O), OC(O), C(O)O, NHC(O), C(O)NH, NHCH2, CH2, CH2NH or CH2O, NHCH(Ra)C(O), —C(O)—CH(Ra)—NH—, CO, CH═N—O,
• L2A, L2B, L3A, L3B, L4A, L4B, L5A, L5B and L5C are each independently for each occurrence a carbohydrate, a carbohydrate analog, glucose, mannose, galactose, N-acetyl-galactosamine, fucose, glucosamine, lactose, maltose, folate or a peptide;
• R′ and R″ are each independently H, CH3, OH, SH, NH2, NR10R20, alkyl, alkenyl or alkynyl;
• Ra is H or amino acid side chain;
• R10 and R20 are each independently alkyl, alkenyl or alkynyl;
• L6A and L6B are each independently alkyl, alkenyl or alkynyl, each of which is optionally substituted with one or more substituents;
• m represent independently for each occurrence 0-50;
• n represent independently for each occurrence 1-20;
• and
• p represent independently for each occurrence 0-50.