Harnessing an emissive guanine surrogate to design small-molecule fluorescent chemosensors of O6-methylguanine-DNA-methyltransferase (MGMT)

Org Biomol Chem. 2022 Mar 2;20(9):1888-1892. doi: 10.1039/d2ob00208f.

Abstract

The fluorescence properties of an emissive guanine surrogate, thienoguanine (thGN, 2-aminothieno[3,4-d]pyrimidin-4(3H)-one), were exploited to design two real-time chemosensors of O6-methylguanine-DNA-methyltransferase (MGMT), a key DNA repair enzyme involved in the resistance to DNA-alkylating anti-cancer drugs though direct reversal of O6-alkylated guanine adducts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Modification Methylases / metabolism*
  • DNA Repair Enzymes / metabolism*
  • Drug Design*
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism*
  • Guanine / analogs & derivatives
  • Guanine / chemistry
  • Guanine / metabolism*
  • Humans
  • Molecular Structure
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / metabolism*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Fluorescent Dyes
  • Small Molecule Libraries
  • Tumor Suppressor Proteins
  • Guanine
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes