Different reactivity of Sp and Rp isomers of phosphorothioate-modified oligonucleotides in a duplex structure

Md Ariful Islam; Aki Fujisaka; Junji Kawakami; Takao Yamaguchi; Satoshi Obika

doi:10.1016/j.bmcl.2020.127166

Different reactivity of Sp and Rp isomers of phosphorothioate-modified oligonucleotides in a duplex structure

Bioorg Med Chem Lett. 2020 Jul 15;30(14):127166. doi: 10.1016/j.bmcl.2020.127166. Epub 2020 Apr 3.

Authors

Md Ariful Islam¹, Aki Fujisaka², Junji Kawakami³, Takao Yamaguchi⁴, Satoshi Obika⁵

Affiliations

¹ Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali 3814, Bangladesh.
² Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Faculty of Pharmacy, Osaka Ohtani University, Nishikiori-Kita 3-11-1, Tondabayashi, Osaka 584-8540, Japan.
³ Faculty of Frontiers of Innovative Research in Science and Technology, Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
⁴ Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
⁵ Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: obika@phs.osaka-u.ac.jp.

PMID: 32527537
DOI: 10.1016/j.bmcl.2020.127166

Abstract

The presence of a stereoisomeric center at the phosphorus atom in phosphorothioate-modified oligonucleotides (PS-ONs) has been recognized as an important feature since the early stages of their development. Therefore, several studies have been conducted on the chirality of PS-ONs. In this study, we evaluated the stereo-biased chemistry of PS-ON duplexes. Depending on their absolute configurations, PS-ON duplexes were found to have significantly different and stereospecific reactivities towards simple alkylating reagent.

Keywords: Alkylation reaction; Oligonucleotide; Phosphorothioate; Stereoselectivity.

Publication types

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

MeSH terms

Carbohydrate Conformation
Phosphorothioate Oligonucleotides / chemistry*
Stereoisomerism

Substances

Phosphorothioate Oligonucleotides