Synthesis and biological evaluation of peptide-siRNA conjugates with phosphodiester unit as linker
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.
KeywordssiRNA peptide conjugate solid synthesis
Unable to display preview. Download preview PDF.
- 19.Moschos SA, Jones SW, Perry MM, Williams AE, Erjefalt JS, Turner JJ, Barnes PJ, Sproat BS, Gait MJ, Lindsay MA. Lung delivery studies using siRNA conjugated to TAT(48–60) and penetratin reveal peptide induced reduction in gene expression and induction of innate immunity. Bioconjugate Chem, 2007, 18: 1450–1459CrossRefGoogle Scholar