Solution Conformation of CCK9, a Cholecystokinin Analog

Cholecystokinin (CCK) is a peptide hormone endowed with several important biological activities, both in the central and peripheral nervous system. Previous conformational studies have dealt mainly with its C-terminal octapeptide fragment (CCK8), which represents the shortest fully circulating form of this hormone. We have undertaken a detailed NMR conformational study in a DMSO d6/H 2O cryomixture at 278 K of the CCK analog H-Arg-Asp-Tyr(SO 3H)-Thr-Gly-Trp-Nle-Asp-PheNH 2 (CCK9) which retains all the bioactivities of CCK8, but was found to he remarkably more stable in acidic media and unaffected by air oxidation due to Met replacements. The predominant conformation contains a γ-turn centered on Thr 4, separated by Gly 5 from a helical segment that comprises the C-terminal residues.