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

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.