Core modified 8-17 DNAzymes with 2'-deoxy-2'-C-methylpyrimidine nucleosides

Bioorg Chem. 2020 Nov:104:104328. doi: 10.1016/j.bioorg.2020.104328. Epub 2020 Sep 29.

Abstract

The catalytic core of an 8-17 DNAzyme directed against STAT 3 was modified using (2'R) and (2'S) 2'-deoxy-2'-C-methyluridine and cytidine. While 2'-deoxy-2'-C-methyluridine significantly diminished the catalytic activity, 2'-deoxy-2'-C-methylcytidine replacement was better accepted, being the kact of modified DNAzymes at 8- and 11-positions comparable to the non-modified one. When 2'-O-methyl and phosphorothioate nucleotides were tested in the binding arms together with core modified DNAzymes the kcat was affected in a non predictable way, emphasizing the fact that both chemical substitutions should be considered globally. Finally, 2'-deoxy-2'-C-methyl modified DNAzymes stability was assayed finding that the double 2'-C-methyl modification in the catalytic core enhanced 70% the stability against a T47D cell lysate compared to a non-modified control.

Keywords: 2′-Deoxy-2′-C-methylpyrimidine nucleotides; 8–17 DNAzyme; Activity; STAT 3; Stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • DNA, Catalytic / chemistry
  • DNA, Catalytic / metabolism*
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / chemistry
  • Deoxycytidine / metabolism
  • Molecular Structure
  • Uridine / analogs & derivatives
  • Uridine / chemistry
  • Uridine / metabolism

Substances

  • (2'S)-2'-deoxy-2'-C-methyluridine
  • DNA, Catalytic
  • Deoxycytidine
  • 2'-methyl-2'-deoxycytidine
  • Uridine