| 摘要 |
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(RN) 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-L6-Q'-L7-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-L6-Q'-L7-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; L6 and L7 are each independently for each occurrence -(CH2)n-, -C(R')(R'')(CH2)n-, -(CH2)nC(R')(R'')-, -(CH2CH2O)mCH2CH2-, or -(CH2CH2O)mCH2CH2NH-; Q' is NH, O, S, CH2, C(O)O, C(O)NH, -NH-CH(Ra)-C(O)-, -C(O)-CH(Ra)-NH-, CO, where Ra is H or amino acid side; chain. R' and R'' are each independently H, CH3, OH, SH, NH2, NH(Alkyl=Me, Et, Pr, isoPr, Bu, Bn) or N(diAlkyl=Me2, Et2, Bn2); 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. |
