| 主权项 |
1. A conjugate comprising an oligonucleotide agent and a ligand represented by Rd, wherein at least one subunit having a formula (I) is incorporated into said oligonucleotide agent: wherein: X is N(CO)R7, NR7 or CH2; Y is NR8, O, S, CR9R10, or absent; Z is CR11R12 or absent; Each of R1, R2, R3, R4, R9, and R10 is, independently, H, ORa, ORb, (CH2)nORa, or (CH2)nORb, provided that at least one of R1, R2, R3, R4, R9, and R10 is ORa or ORb and that at least one of R1, R2, R3, R4, R9, and R10 is (CH2)nORa, or (CH2)nORb; Each of R5, R6, R11, and R12 is, independently, H, C1-C6 alkyl optionally substituted with 1-3 R13, or C(O)NHR7; or R5 and R11 together are C3-C8 cycloalkyl optionally substituted with R14; R7 is Rd; or C1-C20 alkyl substituted with NRcRd or NHC(O)Rd; R8 is C1-C6 alkyl; R13 is hydroxy, C1-C4 alkoxy, or halo; R14 is NRcR7; Ra is: H or Rb is: Each of A and C is, independently, O or S; B is OH, O−, or Rc is H or C1-C6 alkyl; Rd is a carbohydrate radical or a steroid radical optionally tethered to at least one carbohydrate radical; and n is 1-4, wherein the oligonucleotide agent can target a substantially complementary miRNA. |
