New oligodeoxynucleotide derivatives containing N-(methanesulfonyl)-phosphoramidate (mesyl phosphoramidate) internucleotide group

B. P. Chelobanov, E. A. Burakova, D. V. Prokhorova, A. A. Fokina, D. A. Stetsenko

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Novel oligonucleotide derivatives containing N-(methanesulfonyl)-phosphoramidate (mesyl phosphoramidate) group have been described. Solid-phase synthesis of these compounds using an automated DNA synthesizer has been performed for the first time, including the Staudinger reaction between methanesulfonyl azide (mesyl azide) and 3′,5′-dinucleoside 2-cyanoethyl phosphite within an oligonucleotide immobilized on the polymer support, which is a product of phosphoramidite coupling. The mesyl phosphoramidate group is stable to the conditions of oligonucleotide synthesis, in particular, during acidic detritylation and subsequent removal of protecting groups and cleavage of an oligonucleotide from the polymer support by concentrated aqueous ammonia or methylamine at 55°C. It has been shown that the stability of complementary duplexes of oligodeoxynucleotides containing the mesyl phosphoramidate group with a single-stranded DNA is not inferior to the stability of native DNA:DNA duplex. Furthermore, mesyl phosphoramidate oligonucleotides are able to form a complementary duplex with RNA, which is only slightly less stable than the equivalent DNA:RNA duplex. This raises the possibility of their application as potential antisense therapeutic agents.

Original languageEnglish
Pages (from-to)664-668
Number of pages5
JournalRussian Journal of Bioorganic Chemistry
Volume43
Issue number6
DOIs
Publication statusPublished - 1 Nov 2017

Keywords

  • antisense oligonucleotides
  • methanesulfonyl azide
  • solid-phase synthesis
  • Staudinger reaction
  • THERAPEUTICS
  • OLIGODEOXYRIBONUCLEOTIDE

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