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)

191855.pdf - Accepted Version



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.
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 (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

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