Structurally similar small molecule photoaffinity CCK-A agonists and antagonists as novel tools for directly probing 7TM receptors-ligand interactions.
Incorporation of photolabile benzoyl (2a-d) or trifluoromethyl-3H-diazirine (3a-d) substituents into 1,5-benzodiazepine ligands did not significantly impair the rat CCK-A binding affinity of either agonists or antagonists. The modified agonist ligands also retained functional potency and efficacy in the rat amylase assay. Despite their strong structural similarity, the SAR of this limited set of compounds suggests that these small molecule antagonists and agonists might differ in their mode of binding to the CCK-A receptor. Preliminary affinity results show that representative agonists and antagonists from these series can be used to efficiently covalently label the CCK-A receptor.
Darrow
J W
JW
Neurogen Corporation, Branford, CT 06405, USA.
Hadac
E M
EM
Miller
L J
LJ
Sugg
E E
EE
D000818:Animals; D002460:Cell Line; D008024:Ligands; D015335:Molecular Probes; D019920:Photoaffinity Labels / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
D008024:Ligands; D015335:Molecular Probes; D019920:Photoaffinity Labels; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin