Synthesis and biological evaluation of cyclic and branched peptide analogues as ligands for cholecystokinin type 1 receptor

摘要

A library of cyclic CCK8 analogues, containing unnatural amino acids in the peptide sequence, is prepared using solid-phase synthesis. The structure of these cyclic peptides is based on a previously synthesised compound, cyclo-CCK8, selective for CCK_1 receptor. Structure-activity investigations are performed by evaluating the binding properties of the new analogues. In particular, the binding ability of the cyclic CCK8 analogues is tested by nuclear medicine studies on cell line transfected with CCK_1 receptor. Compounds named cyclo-A4-cyclo-A7 show binding constant in the range 6.0-8.0 μM, with an improved affinity over the previous described cyclo-CCK8, but almost comparable IC_(50) values among new analogues towards CCK_1 were obtained.