Solid phase synthesis of peptide–siRNA conjugates containing disulfide bond unit

Abstract

Abstract A disulfide-modified nucleoside was designed and synthesized. After loading the modified nucleoside on controlled pore glass (CPG), solid phase synthesis strategy was used to prepare peptide–oligonucleotide conjugates (N-3′) containing disulfide bond unit. The 3′-sense strand peptide–siRNA conjugate ( VII ) maintained good gene silencing activity, while that of the 3′-antisense strand conjugate decreased somewhat. And the sense strand off-target effect of VII decreased remarkably.