CYCLIC CHOLECYSTOKININ-ANALOG PENTAPEPTIDE CYCLO (ASP-TRP-MET-ASP-PHE) - AN UNEXPECTED SOLUTION CONFORMATION

The conformational analysis of the CCK-B binding peptide cycle (Asp-Tr p-Met-Asp-Phe) has been carried out in DMSO-d(6) and in a mixture of H 2O/DMSO-d(6) by NMR spectroscopy and by restrained molecular dynamics methods. In the NMR spectra, only one set of resonance signals was fou nd. The NOE analyses proved the existence of an all-trans conformation for this peptide. Distance constraints of H-1 pairs derived from NOE data were used for restrained molecular dynamics simulations, resultin g in one conformational family with a very regular orientation of-the amino acids and similar dihedral angles for each residue. The dihedral s and the absence of an intramolecular hydrogen bond indicate that the re is no common turn formation in the peptide backbone. A submicromola r binding constant for CCK-B receptors point to a similarity with the bioactive conformation. (C) 1995 Academic Press, Inc.