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 conjugat...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.展开更多
In this paper,a series of peptide-siRNA conjugates with phosphodiester unit as the linker targeting to Cdc2 gene were synthesized by solid phase stepwise strategy.The conjugation of peptides at either 3’-terminus of ...In this paper,a series of peptide-siRNA conjugates with phosphodiester unit as the linker targeting to Cdc2 gene were synthesized by solid phase stepwise strategy.The conjugation of peptides at either 3’-terminus of siCdc2 bring no change to the classical A-form of RNA duplex,but slightly compromise the thermodynamic stability.Peptide conjugation at the 3’-terminus of sense strand could improve the serum stability obviously,however,the opposite peptide conjugation at the 3’-terminus of antisense strand shows no such influence.According to the results of artificial silencing activity assay system,peptide conjugation at 3’-terminus of antisense strand slightly weakens the silencing activity of siCdc2.But sense strand peptide conjugation exhibits similar silencing activity as native siCdc2,meanwhile,it could mitigate the unwanted off-target effect of sense strand targeting to its own mRNA.展开更多
基金supported by the National Natural Science Foundation of China(No.20932001)the Ministry of Science and Technology of China(Nos.2012CB720604,2012AA022501)
文摘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.
基金supported by the National Natural Science Foundation of China(20932001)the Ministry of Science and Technology of China(2012AA022501)the National Key Basic Research Program of China(2012CB720604)
文摘In this paper,a series of peptide-siRNA conjugates with phosphodiester unit as the linker targeting to Cdc2 gene were synthesized by solid phase stepwise strategy.The conjugation of peptides at either 3’-terminus of siCdc2 bring no change to the classical A-form of RNA duplex,but slightly compromise the thermodynamic stability.Peptide conjugation at the 3’-terminus of sense strand could improve the serum stability obviously,however,the opposite peptide conjugation at the 3’-terminus of antisense strand shows no such influence.According to the results of artificial silencing activity assay system,peptide conjugation at 3’-terminus of antisense strand slightly weakens the silencing activity of siCdc2.But sense strand peptide conjugation exhibits similar silencing activity as native siCdc2,meanwhile,it could mitigate the unwanted off-target effect of sense strand targeting to its own mRNA.
