Structurally similar small molecule photoaffinity CCK-A agonists and antagonists as novel tools for directly probing 7TM receptor-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. Th e 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 antago nists and agonists might differ in their mode of binding to the CCK-A recep tor. Preliminary affinity results show that representative agonists and ant agonists from these series can be used to efficiently covalently label the CCK-A receptor. (C) 1998 Elsevier Science Ltd. All rights reserved.