Molecular construction of sulfonamide antisense oligonucleotides

Valerijs Korotkovs, Linus F. Reichenbach, Clémentine Pescheteau, Glenn A. Burley, Rob M. J. Liskamp

Research output: Contribution to journalArticle

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 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 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.
LanguageEnglish
Pages10635-10648
Number of pages14
JournalJournal of Organic Chemistry
Volume84
Issue number17
Early online date5 Aug 2019
DOIs
Publication statusPublished - 6 Sep 2019

Fingerprint

Antisense Oligonucleotides
Sulfonamides
RNA
DNA
Monomers
Oligomers
Oligonucleotides
Melting point
Thermodynamic stability

Keywords

  • oligonucleotide monomers
  • RNA
  • sulfonamide antisense oligonucleotides
  • SaASOs
  • DNA

Cite this

Korotkovs, V., Reichenbach, L. F., Pescheteau, C., Burley, G. A., & Liskamp, R. M. J. (2019). Molecular construction of sulfonamide antisense oligonucleotides. Journal of Organic Chemistry, 84(17), 10635-10648. https://doi.org/10.1021/acs.joc.9b00941
Korotkovs, Valerijs ; Reichenbach, Linus F. ; Pescheteau, Clémentine ; Burley, Glenn A. ; Liskamp, Rob M. J. / Molecular construction of sulfonamide antisense oligonucleotides. In: Journal of Organic Chemistry. 2019 ; Vol. 84, No. 17. pp. 10635-10648.
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Korotkovs, V, Reichenbach, LF, Pescheteau, C, Burley, GA & Liskamp, RMJ 2019, 'Molecular construction of sulfonamide antisense oligonucleotides' Journal of Organic Chemistry, vol. 84, no. 17, pp. 10635-10648. https://doi.org/10.1021/acs.joc.9b00941

Molecular construction of sulfonamide antisense oligonucleotides. / Korotkovs, Valerijs; Reichenbach, Linus F.; Pescheteau, Clémentine; Burley, Glenn A.; Liskamp, Rob M. J.

In: Journal of Organic Chemistry, Vol. 84, No. 17, 06.09.2019, p. 10635-10648.

Research output: Contribution to journalArticle

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T1 - Molecular construction of sulfonamide antisense oligonucleotides

AU - Korotkovs, Valerijs

AU - Reichenbach, Linus F.

AU - Pescheteau, Clémentine

AU - Burley, Glenn A.

AU - Liskamp, Rob M. J.

PY - 2019/9/6

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AB - 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 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 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.

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KW - RNA

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KW - DNA

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