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Synthesis and properties of novel L-isonucleoside modified oligonucleotides and siRNAs
Zhang, Jun; Chen, Yue; Huang, Ye; Jin, Hong-Wei; Qiao, Ren-Ping; Xing, Lei; Zhang, Liang-Ren; Yang, Zhen-Jun; Zhang, Li-He
刊名ORGANIC & BIOMOLECULAR CHEMISTRY
2012
DOI10.1039/c2ob26219c
10期:37页:7566-7577
收录类别SCI ; IC
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Organic
资助者National Natural Science Foundation of China ; Ministry of Science and Technology of China ; National Natural Science Foundation of China ; Ministry of Science and Technology of China
研究领域[WOS]Chemistry
关键词[WOS]LOCKED NUCLEIC-ACID ; HYBRIDIZATION PROPERTIES ; CHEMICAL-MODIFICATION ; ENZYMATIC STABILITY ; HIGH-AFFINITY ; GUIDE STRAND ; RNASE-H ; DNA ; COMPLEXES ; OLIGODEOXYNUCLEOTIDES
英文摘要

Antisense oligonucleotides and siRNAs are potential therapeutic agents and their chemical modifications play an important role to improve the properties and activities of oligonucleotides. Isonucleoside is a type of nucleoside analogue, in which the nucleobase is moved from C-1 to other positions of ribose. In this report, a novel isonucleoside 5 containing a 5′-CH2-extended chain at the sugar moiety was synthesized, thus isoadenosine 5a and isothymidine 5b were incorporated into a DNA single strand and siRNA. It was found that isonucleoside 5 modified oligonucleotides can form stable double helical structures with their complementary DNA and RNA and the stability towards nuclease and ability to activate RNase H are more promising compared with the unmodified, natural analogues. In siRNA, passenger strand modified with isonucleoside (5a/b) at 3′ or 5′ terminal can retain the silencing activity and minimize the passenger strand specific off-target effect.

语种英语
所属项目编号20932001 ; 2006AA02Z144 ; 2009ZX09503
资助者National Natural Science Foundation of China ; Ministry of Science and Technology of China ; National Natural Science Foundation of China ; Ministry of Science and Technology of China
WOS记录号WOS:000308089500015
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54292
专题北京大学药学院
作者单位Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
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GB/T 7714
Zhang, Jun,Chen, Yue,Huang, Ye,et al. Synthesis and properties of novel L-isonucleoside modified oligonucleotides and siRNAs[J]. ORGANIC & BIOMOLECULAR CHEMISTRY,2012,10(37):7566-7577.
APA Zhang, Jun.,Chen, Yue.,Huang, Ye.,Jin, Hong-Wei.,Qiao, Ren-Ping.,...&Zhang, Li-He.(2012).Synthesis and properties of novel L-isonucleoside modified oligonucleotides and siRNAs.ORGANIC & BIOMOLECULAR CHEMISTRY,10(37),7566-7577.
MLA Zhang, Jun,et al."Synthesis and properties of novel L-isonucleoside modified oligonucleotides and siRNAs".ORGANIC & BIOMOLECULAR CHEMISTRY 10.37(2012):7566-7577.
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