Incorporation of an acyclic alkynyl nucleoside analog into siRNA improves silencing activity and nuclease resistance

Aya Ogata; Yoshihito Ueno

doi:10.1016/j.bmcl.2015.04.034

Incorporation of an acyclic alkynyl nucleoside analog into siRNA improves silencing activity and nuclease resistance

Bioorg Med Chem Lett. 2015 Jun 15;25(12):2574-8. doi: 10.1016/j.bmcl.2015.04.034. Epub 2015 Apr 17.

Authors

Aya Ogata¹, Yoshihito Ueno²

Affiliations

¹ United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
² United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan. Electronic address: uenoy@gifu-u.ac.jp.

PMID: 25956414
DOI: 10.1016/j.bmcl.2015.04.034

Abstract

In order to improve the silencing activity and nuclease resistance of small interfering RNA (siRNA), we designed and synthesized an acyclic thymidine analog containing 4-pentyne-1,2-diol instead of d-ribofuranose. The incorporation of this analog into siRNAs at specific positions in the strands was found to enhance the silencing activity of siRNAs and to increase the resistance of the siRNA to hydrolytic degradation by a 3' exonuclease.

Keywords: Acyclic nucleoside; Alkyne; Nuclease resistance; RNAi; siRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Endonucleases / antagonists & inhibitors
Endonucleases / genetics
Endonucleases / metabolism*
Hydrolysis
Nucleosides / chemistry*
Oligonucleotides / chemical synthesis
Oligonucleotides / chemistry
RNA, Small Interfering / chemistry*
RNA, Small Interfering / metabolism

Substances

Nucleosides
Oligonucleotides
RNA, Small Interfering
Endonucleases