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A disulfde-modifed nucleoside was designed and synthesized. After loading the modifed nucleoside on controlled pore glass(CPG), solid phase synthesis strategy was used to prepare peptide–oligonucleotide conjugates(N-3’) containing disulfde 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.
A disulfde-modifed nucleoside was designed and synthesized. After loading the modifed nucleoside on controlled pore glass (CPG), solid phase synthesis strategy was used to prepare peptide-oligonucleotide conjugates (N-3 ’) containing disulfde 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.