Study of the Staudinger Reaction and Reveal of Key Factors Affecting the Efficacy of Automatic Synthesis of Phosphoryl Guanidinic Oligonucleotide Analogs

M. A. Bazhenov, A. V. Shernyukov, M. S. Kupryushkin, D. V. Pyshnyi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

In this work, we introduce a novel nuanced analysis of the chemical transformations occurs during the automatic synthesis of phosphoryl guanidine oligonucleotides (PGOs). It was shown on model compounds that the stable form of phosphoryl guanidine afforded by the P(III) atom of the phosphite component oxidation by the corresponding organic azide is the positively charged triester phosphoryl guanidinium fragment. The idea that the presence of such kind of fragments in PGOs, obtained under automatic DNA synthesis conditions, may have an adverse effect on its backbone stability when at the postsynthetic stage PGOs on polymer treated with aqueous basic solutions has been proposed. To overcome this impediment, we suggest before the stage of the desired PGO final deblocking to treat the solid phase with a protected PGO chain fixed with a solution of a strong base in an anhydrous medium. In consequence of this treatment, the transformation of PGO triester form to diester takes place, imparting better stability to the modified chain under deblocking conditions and increasing the yield of the desired oligonucleotide derivatives.

Original languageEnglish
Pages (from-to)699-708
Number of pages10
JournalRussian Journal of Bioorganic Chemistry
Volume45
Issue number6
DOIs
Publication statusPublished - 1 Nov 2019

Keywords

  • automated oligonucleotide synthesis
  • modified oligonucleotides
  • organic azides
  • phosphoazides
  • phosphoryl guanidine oligonucleotides (PGO)
  • phosphoryl guanidines
  • Staudinger reaction

OECD FOS+WOS

  • 1.06.CQ BIOCHEMISTRY & MOLECULAR BIOLOGY
  • 1.04 CHEMICAL SCIENCES

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