BINDING OF CHOLECYSTOKININ-8 (CCK-8) PEPTIDE DERIVATIVES TO CCK(A) AND CCK(B) RECEPTORS

The structural requirements for the selective binding of cholecystokin in-8 (CCK-8)-related peptides to peripheral (CCK(A)) receptors are not sufficiently understood. In this study, the interaction of a series o f newly shortened analogues of CCK-8 with both receptor subtypes was a nalyzed by displacement studies using [H-3]-CCK-8 and I-125-Bolton-Hun ter (BH)-CCK-8 as radioligands. The pentapeptide derivative of CCK-8, succinyl-Tyr (SO3H)-Met-Gly-Trp-Met-phenethylamide, was found to bind selectively with high affinity to the CCK(A) receptor. The replacement of Met28 and/or Met31 by norleucine and of L-Trp30) by its D-analogue had no significant effect on the binding properties of the peptide. F urther C-terminal shortening resulted in a drastic loss of affinity an d selectivity of the CCK receptor binding.