Loss of silencing activity caused by 5′-terminal modification with D-/L-isonucleotide(isoNA) or locked nucleic acid(LNA) could not be restored by 5′-terminal phosphorylation  

作　　者：HUANG Ye CHEN Zhuo WANG Zhuo LI YaTing CHEN Yue YANG ZhenJun ZHANG LiHe 

机构地区：[1]The State Key Laboratory of Natural and Biomimetic Drugs [2]School of Pharmaceutical Sciences,Peking University

出　　处：《Science China Chemistry》2014年第2期329-334,共6页中国科学（化学英文版）

基　　金：supported by the National Natural Sciences Foundation of China(20932001);the Program of the Ministry of Science and Technology of China(2009ZX09503,2012AA022501,2012CB720604)

摘　　要：In this study,a series of 5′-phosphorylated siRNAs with D-/L-isonucleotide(isoNA)or locked nucleic acid(LNA)incorporated at the 5′-terminus were synthesized.It was found that after incorporating either isoNA or LNA at the 5′-terminus of the antisense strand or sense strand,the silencing activity of modified strands has been inhibited,which cannot be recovered by phosphorylation at the 5′-terminus;however,the silencing activity of unmodified strand to its own target was increased.This work indicates that the isoNA and LNA modification at 5′-terminus can interfere with the strand selection during the RISC assembling process,and the disturbance of the 5′-phosporylation should not be the only viable mechanism.In this study, a series of 5＇-phosphorylated siRNAs with D-/L-isonucleotide （isoNA） or locked nucleic acid （LNA） incorporated at the 5＇-terminus were synthesized. It was found that after incorporating either isoNA or LNA at the 5＇-terminus of the anti sense strand or sense strand, the silencing activity of modified strands has been inhibited, which cannot be recovered by phos- phorylation at the 5＇-terminus; however, the silencing activity of unmodified strand to its own target was increased. This work indicates that the isoNA and LNA modification at 5＇-terminus can interfere with the strand selection during the RISC assem- bling process, and the disturbance of the 5＇-phosporylation should not be the only viable mechanism.

关 键 词：isonucleotide locked nucleic acid （LNA） 5＇-terminal phosphorylation 

分 类 号：Q522[生物学—生物化学]