Molecular construction of sulfonamide antisense oligonucleotides

Korotkovs, V., Reichenbach, L. F., Pescheteau, C., Burley, G. A. and Liskamp, R. M.J. (2019) Molecular construction of sulfonamide antisense oligonucleotides. Journal of Organic Chemistry, 84(17), pp. 10635-10648. (doi: 10.1021/acs.joc.9b00941)

Abstract

An efficient and scalable synthesis of new oligonucleotide monomers was developed for replacement of the phosphodiester backbone of RNA by a sulfonamide containing backbone to enable construction of novel sulfonamide antisense oligonucleotides (SaASOs). It was shown that by employing these sulfonamide RNA(SaRNA) monomers it was possible to synthesize oligomers in solution. The properties of a sulfonamide moiety replacement were evaluated by incorporation of a SaRNA-monomer into a DNA strand and performing thermal stability tests of the resulting DNA and RNA-double-strand hybrids. Although the sulfonamide modification caused a decrease in melting temperature (Tm) of both hybrids, it was lower for the sulfonamide containing DNA-RNA hybrid than that for the sulfonamide containing DNA-DNA hybrid.

• Item Type: Articles
• Additional Information: This research was funded by the University of Glasgow.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liskamp, Professor Robert and Burley, Dr Glenn and Korotkovs, Mr Valerijs
• Authors: Korotkovs, V., Reichenbach, L. F., Pescheteau, C., Burley, G. A., and Liskamp, R. M.J.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Journal of Organic Chemistry
• Publisher: American Chemical Society
• ISSN: 0022-3263
• ISSN (Online): 1520-6904
• Published Online: 05 August 2019
• Copyright Holders: Copyright © 2019 American Chemical Society
• First Published: First published in Journal of Organic Chemistry 84(17):10635–10648
• Publisher Policy: Reproduced in accordance with the publisher copyright policy