Modification of receptor selectivity and functional activity of cyclic cholecystokinin analogues

Article abstract of DOI:10.1016/S0223-5234(98)80006-8

We reported earlier on the synthesis and biological activity at the CCK-B receptor of cyclized derivatives of CCK. These peptides, in which the positions 28 and 31 were replaced by lysine residues, were bridged by a succinyl moiety. To determine the importance of the nature and size of the cyclic structure, cyclic analogues were synthesized in which: (i) the lysine residues were replaced by ornithine and diaminobutyric acid and (ii) the succinic moiety was replaced by a malonic, adipic and glutaric moiety. They were tested For their ability to inhibit the specific binding of ¹²⁵I-BH-CCK-8 to CCK receptors in rat pancreatic acini and guinea pig brain membranes. They were also evaluated for their ability to stimulate amylase secretion from rat pancreatic acini. The potency and selectivity of these analogues were compared with those obtained with CCK-4 and compound JIMV320, a potent and selective CCK-B receptor ligand synthesized earlier in our laboratory.