Synthesis,physicochemical and biological properties of oligonucleotides incorporated with amino-isonucleosides  

作　　者：WANG Fang CHEN Yue HUANG Ye JIN Hong-Wei ZHANG Liang-Ren YANG Zhen-Jun ZHANG Li-He 

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences,Peking University,Beijing 100191,China

出　　处：《Science China Chemistry》2012年第1期70-79,共10页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China(20932001);the Ministry of Science and Technology of China (2006AA02Z144,2009ZX09503)

摘　　要：Antisense oligonucleotides(ASONs) and siRNAs have been applied extensively for the regulation of cellular and viral gene expression,and RNAi is currently one of the most promising new approaches for anti-tumor and anti-viral therapy.In order to improve bioactivity properties and physicochemical properties of siRNA,we synthesized a novel class of ASONs II-VII incorporated with amino-isonucleoside(isoA1 and isoA2) for investigation on basic physicochemical properties.Then we designed amino-isonucleoside(isoA1,isoA2 and isoT1) incorporated siRNA 2-7.Some meaningful results have been obtained from the physicochemical property experiments in ASONs.In RNAi potency experiments,we investigated RNAi potency of each strand of the siRNA.These amino-isonucleosides incorporated siRNAs showed promising bioactivity properties and had position specificity.Reduced off target effect from sense strand loading in siRNA application was observed.Antisense oligonucleotides（ASONs） and siRNAs have been applied extensively for the regulation of cellular and viral gene expression,and RNAi is currently one of the most promising new approaches for anti-tumor and anti-viral therapy.In order to improve bioactivity properties and physicochemical properties of siRNA,we synthesized a novel class of ASONs II-VII incorporated with amino-isonucleoside（isoA1 and isoA2） for investigation on basic physicochemical properties.Then we designed amino-isonucleoside（isoA1,isoA2 and isoT1） incorporated siRNA 2-7.Some meaningful results have been obtained from the physicochemical property experiments in ASONs.In RNAi potency experiments,we investigated RNAi potency of each strand of the siRNA.These amino-isonucleosides incorporated siRNAs showed promising bioactivity properties and had position specificity.Reduced off target effect from sense strand loading in siRNA application was observed.

关 键 词：amino-isonucleoside antisense oligonucleotide SIRNA 

分 类 号：O621.2[理学—有机化学]