Synthesis of γ-N-modified 8-oxo-2'-deoxyguanosine triphosphate and its characterization

Nucleosides Nucleotides Nucleic Acids. 2019;38(8):578-589. doi: 10.1080/15257770.2019.1586919. Epub 2019 Mar 31.

Abstract

8-OxodGTP is generated by the reaction between dGTP and reactive oxygen species and a considered mutagenic nucleotide. It can be incorporated into the duplex DNA during replication processes by the DNA polymerase, and thus the repair enzyme removes oxodGTP from the nucleotide pools in living cells. On the other hand, the γ-modified triphosphates show interesting properties for use as biological tools. Therefore, the γ-N-pyrenylalkyl-oxodGTP derivatives were synthesized and their effect on the enzymatic reactions were evaluated. The γ-N-pyrenylmethyl-oxodGTP was found to be accepted by the DNA polymerase just like oxodGTP, but showed a competitive inhibition property for the human oxodGTPase.

Keywords: 8-oxodGTP; DNA polymerase; gamma phosphate modification; repair enzyme.

MeSH terms

  • DNA-Directed DNA Polymerase / chemistry
  • Deoxyguanine Nucleotides / chemical synthesis*
  • Deoxyguanine Nucleotides / chemistry
  • Humans
  • Hydrolysis
  • Kinetics
  • Molecular Docking Simulation
  • Molecular Structure
  • Oxidation-Reduction
  • Pyrenes / chemical synthesis*
  • Pyrenes / chemistry

Substances

  • Deoxyguanine Nucleotides
  • Pyrenes
  • 8-oxodeoxyguanosine triphosphate
  • DNA-Directed DNA Polymerase