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.
Heckendorn
R
R
Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
Allgeier
H
H
Baud
J
J
Gunzenhauser
W
W
Angst
C
C
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000378:metabolism; D000345:Affinity Labels; D000818:Animals; D001386:Azides / Q000138:chemical synthesis* / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000378:metabolism; D010777:Photochemistry; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000345:Affinity Labels; D001386:Azides; D005971:Glutamates; D007457:Iodine Radioisotopes; D009943:Organophosphorus Compounds; D016194:Receptors, N-Methyl-D-Aspartate; C069052:CGP 39653; C083277:CGP 55802A; D018698:Glutamic Acid; D015763:2-Amino-5-phosphonovalerate