Synthesis and binding properties of 2-amino-5-phosphono-3-pentenoic acid photoaffinity ligands as probes for the glutamate recognition site of the NMDA receptor

J Med Chem. 1993 Nov 12;36(23):3721-6. doi: 10.1021/jm00075a029.

Abstract

Four omega-benzoylated (E)-2,10-diamino-4-(phosphonomethyl)dec-3-enoic acids have been synthesized and tested in vitro for binding affinity to the glutamate recognition site of the NMDA (N-methyl-D-aspartate) receptor. The omega-4-azidosalicylamide derivative 24 was iodinated to give the photoaffinity ligand 25 (CGP 55802 A) which showed an IC50 value of 34 nM in the in vitro [3H]CGP 39653 binding assay. This compound and its radioactive 125I-form are the first photoaffinity ligands for the NMDA receptor with high affinity to the glutamate recognition site.

MeSH terms

  • 2-Amino-5-phosphonovalerate / analogs & derivatives
  • 2-Amino-5-phosphonovalerate / metabolism
  • Affinity Labels*
  • Animals
  • Azides / chemical synthesis*
  • Azides / metabolism
  • Binding Sites
  • Brain / metabolism
  • Glutamates / metabolism*
  • Glutamic Acid
  • Iodine Radioisotopes
  • Isotope Labeling
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Organophosphorus Compounds / chemical synthesis*
  • Organophosphorus Compounds / metabolism
  • Photochemistry
  • Rats
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Spectrometry, Mass, Fast Atom Bombardment

Substances

  • Affinity Labels
  • Azides
  • Glutamates
  • Iodine Radioisotopes
  • Organophosphorus Compounds
  • Receptors, N-Methyl-D-Aspartate
  • CGP 39653
  • CGP 55802A
  • Glutamic Acid
  • 2-Amino-5-phosphonovalerate