NRAS DNA G-quadruplex-targeting molecules for sequence-selective enzyme inhibition

Chem Commun (Camb). 2024 Nov 7;60(90):13179-13182. doi: 10.1039/d4cc03753g.

Abstract

Sequence-selective G-quadruplex ligands are valuable for controlling gene expression. Here, we established a new fluorescence displacement assay using a NRAS G-quadruplex selective fluorescent probe to identify sequence-selective DNA G-quadruplex ligands. These sequence-selective NRAS G-quadruplex ligands retained their binding affinity even in the presence of excessive human telomeric DNA G-quadruplex and regulated enzymatic activities in a sequence-selective manner.

MeSH terms

  • DNA / chemistry
  • DNA / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Fluorescent Dyes* / chemistry
  • G-Quadruplexes*
  • GTP Phosphohydrolases / chemistry
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Ligands
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism

Substances

  • Ligands
  • Fluorescent Dyes
  • DNA
  • NRAS protein, human
  • Enzyme Inhibitors
  • Membrane Proteins
  • GTP Phosphohydrolases