Folate conjugates

Abstract

The present invention provides iRNA agent including at least one monomer having the structure shown in formula (I') wherein: A and B are each independently for each occurrence O, N(R) or S; X is H, a protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z′)(Z″)O-nucleoside, —P(Z′)(Z″)O-oligonucleotide, a lipid, a PEG, a steroid, a polymer, —P(Z′)(Z″)O-L-Q′-L-OP(Z′″)(Z′″″)O-oligonucleotide, a nucleotide, or an oligonucleotide; Y is H, a protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z′)(Z″)O-nucleoside, —P(Z′)(Z″)O-oligonucleotide, a lipid, a PEG, a steroid, a lipophile, a polymer, —P(Z′)(Z″)O-L-Q′-L-OP(Z′″)(Z′″″)O-oligonucleotide, a nucleotide, or an oligonucleotide; R is folate, a folate analog a folate mimic or a folate receptor binding ligand; Land Lare each independently for each occurrence —(CH)—, —C(R′)(R″)(CH)—, —(CH)C(R′)(R″)—, —(CHCHO)CHCH—, or —(CHCHO)CHCHNH—; Q′ is NH, O, S, CH, C(O)O, C(O)NH, —NH—CH(R)—C(O)—, —C(O)—CH(R)—NH—, CO, where Ris H or amino acid side chain;R′ and R″ are each independently H, CH, OH, SH, NH, NH(Alkyl=Me, Et, Pr, isoPr, Bu, Bn) or N(diAlkyl=Me, Et, Bn); Z′, Z″, Z′″ and Z″″ are independently O or S; n represent independently for each occurrence 1-20; and m represent independently for each occurrence 0-50.