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

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.

Graphical abstractPeptide–oligonucleotide conjugates (N-3′) containing disulfide bond unit has been synthesized by solid phase synthesis strategy. The 3′-sense strand peptide conjugated siRNA(VII) maintained good gene silencing activity, and the sense strand off-target effect decreased remarkably.Figure optionsDownload full-size imageDownload as PowerPoint slide