Synthesis of the new nucleoside 5'-alpha-iminophosphates using Staudinger reaction

Bioorg Chem. 2022 Oct:127:105987. doi: 10.1016/j.bioorg.2022.105987. Epub 2022 Jun 27.

Abstract

Efficient protocols were developed for the synthesis of a new compounds - nucleoside 5'-α-iminophosphates using the Staudinger reaction. These substances are alpha-phosphate mimetic nucleotide in which an oxygen atom is replaced by a corresponding imino (=N-R)-group. Various 5'-iminomonophosphates of nucleosides were obtained. A chemical method for the synthesis of triphosphate derivatives based on the iminomonophosphates has been designed. Thymidine 5'-(1,3-dimethylimidazolidin-2-ylidene)-triphosphate (ppp(DMI)T) was synthesized, its hydrolytic stability and substrate properties in relation to some DNA polymerases was firstly studied. It was shown that ppp(DMI)T can serve as substrate for enzyme catalyzed template-independent DNA synthesis by human terminal deoxynucleotidyltransferase TdT.

Keywords: Alpha-phosphate mimetic nucleotides; Nucleoside 5′-α-iminophosphates; Staudinger reaction; Terminal deoxynucleotidyl transferase substrate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Nucleotidylexotransferase / chemistry
  • DNA-Directed DNA Polymerase* / chemistry
  • Humans
  • Nucleosides* / chemistry
  • Nucleotides / chemistry
  • Thymidine

Substances

  • Nucleosides
  • Nucleotides
  • DNA Nucleotidylexotransferase
  • DNA-Directed DNA Polymerase
  • Thymidine