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 photoaffini...

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Veröffentlicht in:	Journal of medicinal chemistry 1993-11, Vol.36 (23), p.3721-3726
Hauptverfasser:	Heckendorn, Roland, Allgeier, Hans, Baud, Jaqueline, Gunzenhauser, Wilfried, Angst, Christof
Format:	Artikel
Sprache:	eng
Schlagworte:	2-Amino-5-phosphonovalerate - analogs & derivatives 2-Amino-5-phosphonovalerate - metabolism Affinity Labels Animals Azides - chemical synthesis Azides - metabolism Binding Sites Brain - metabolism Chemistry Exact sciences and technology Glutamates - metabolism Glutamic Acid Iodine Radioisotopes Isotope Labeling Magnetic Resonance Spectroscopy Molecular Structure Noncondensed benzenic compounds Organic chemistry Organophosphorus Compounds - chemical synthesis Organophosphorus Compounds - metabolism Photochemistry Preparations and properties Rats Receptors, N-Methyl-D-Aspartate - metabolism Spectrometry, Mass, Fast Atom Bombardment
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Zusammenfassung:	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.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm00075a029