Issue 37, 2012

Synthesis and properties of novel l-isonucleoside modified oligonucleotides and siRNAs

Abstract

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.

Graphical abstract: Synthesis and properties of novel l-isonucleoside modified oligonucleotides and siRNAs

Supplementary files

Article information

Article type
Paper
Submitted
28 Apr 2012
Accepted
31 Jul 2012
First published
02 Aug 2012

Org. Biomol. Chem., 2012,10, 7566-7577

Synthesis and properties of novel L-isonucleoside modified oligonucleotides and siRNAs

J. Zhang, Y. Chen, Y. Huang, H. Jin, R. Qiao, L. Xing, L. Zhang, Z. Yang and L. Zhang, Org. Biomol. Chem., 2012, 10, 7566 DOI: 10.1039/C2OB26219C

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