| 摘要 |
Disclosed is an oligomer comprising a backbone, a 3’ terminus, and a 5’ terminus, the backbone comprising a sequence of morpholine ring structures joined by intersubunit linkages, the morpholino ring structures having a 5’ end and a 3’ end according to the following structure (i), or a salt, tautomer or stereoisomer thereof, wherein B is, at each occurrence, independently a base-pairing moiety, the intersubunit linkages joining the 3’-end of one morpholino ring structure to the 5’- end of an adjacent morpholino ring structure, wherein the intersubunit linkages have the general structure (I), and wherein for at least one of the intersubunit linkages (I), W is, at each occurrence, independently S or O; X is, at each occurrence, independently -NR8R9 or -OR3; and Y is, at each occurrence, independently O or -NR10, R8 is, at each occurrence, independently hydrogen or an optionally substituted C2-C12 saturated or unsaturated hydrocarbon chain radical; R9 is at each occurrence, independently hydrogen, an optionally substituted saturated or unsaturated hydrocarbon chain radical, -Rb-Rc or optionally substituted aryl; R3 is, at each occurrence, independently hydrogen or an optionally substituted saturated or unsaturated hydrocarbon chain radical; R10 is, at each occurrence, independently hydrogen, an optionally substituted saturated or unsaturated hydrocarbon chain radical or -LNR4R5R7, wherein R8 and R9 may join to form a 5-18 membered, optionally substituted, mono or bicyclic heterocycle, or R8, R9 or R3 may join with R10 to form a 5-7 membered, optionally substituted, heterocycle; provided that i) R8 and R9 join to form a 5-18 membered, optionally substituted, mono or bicyclic heterocycle; or ii) R8, R9 or R3 join with R10 to form a 5-7 membered, optionally substituted, heterocycle. The disclosed oligonucleotide analogues are intended to have antisense or antigene performance, including having affinity for DNA and RNA without compromising sequence selectivity; having desirable pharmacokinetics and tissue distribution; and for improved cellular delivery and reliable and controllable in vivo distribution. |
