Reactive derivatives for affinity labeling in the ifenprodil site of NMDA receptors.
To prepare thiol-reactive ifenprodil derivatives designed as potential probes for cysteine-substituted NR2B containing NMDA receptors, electrophilic centers were introduced in different areas of the ifenprodil structure. Intermediates and final compounds were evaluated by binding studies and by electrophysiology to determine the structural requirements for their selectivity. The reactive compounds were further tested for their stability and for their reactivity in model reactions; some were found suitable as structural probes to investigate the binding site and the docking mode of ifenprodil in the NR2B subunit.
Alarcon
Karine
K
Laboratoire de Chimie Bioorganique, CNRS UMR 7175, Faculté de Pharmacie, Université Louis Pasteur de Strasbourg, 74 Route du Rhin, F-67401 Illkirch, France. alarcon@bioorga.u-strasbg.fr
Martz
Adeline
A
Mony
Laetitia
L
Neyton
Jacques
J
Paoletti
Pierre
P
Goeldner
Maurice
M
Foucaud
Bernard
B
D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D000345:Affinity Labels / Q000737:chemistry*; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry; D004594:Electrophysiology; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D008956:Models, Chemical; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000317:Adrenergic alpha-Antagonists; D000345:Affinity Labels; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D003545:Cysteine; C010739:ifenprodil