6-Azido-7-nitro-1,4-dihydroquinoxaline-2,3-dione (ANQX) forms an irreversible bond to the active site of the GluR2 AMPA receptor

J Med Chem. 2008 Sep 25;51(18):5856-60. doi: 10.1021/jm701517b.

Abstract

AMPA receptors mediate fast excitatory synaptic transmission and are essential for synaptic plasticity. ANQX, a photoreactive AMPA receptor antagonist, is an important biological probe used to irreversibly inactivate AMPA receptors. Here, using X-ray crystallography and mass spectroscopy, we report that ANQX forms two major products in the presence of the GluR2 AMPAR ligand-binding core (S1S2J). Upon photostimulation, ANQX reacts intramolecularly to form FQX or intermolecularly to form a covalent adduct with Glu705.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Excitatory Amino Acid Antagonists / chemistry
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Mass Spectrometry
  • Models, Molecular
  • Molecular Structure
  • Nitro Compounds / chemistry
  • Nitro Compounds / pharmacology*
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Receptors, AMPA / antagonists & inhibitors*
  • Receptors, AMPA / chemistry

Substances

  • 6-azido-7-nitro-1,4-dihydroquinoxaline-2,3-dione
  • Excitatory Amino Acid Antagonists
  • Nitro Compounds
  • Quinolines
  • Receptors, AMPA

Associated data

  • PDB/3BKI