Conformational analysis of cholecystokinin fragments CCK₄, CCK₅, and CCK₆ by ¹H‐nmr spectroscopy and fluorescence‐transfer measurements

Abstract

Abstract The confortmational behavior of the cholecystokinin‐related fragments CCK 4 , CCK 5 , and CCK 6 as determined by 1 H‐nmr spectroscopy in DMSO‐d 6 and water and fluorescence‐transfer measurements in aqueous medium are greatly dependent on the ionization states of these peptides. Under netral conditions, the backbones of CCK 5 and CCK 6 preferentially adopted folded forms with a β‐turn including the four residues Gly‐Trp‐Met‐Asp, probably stabilized by a hydrogen bond between the CO of Gly and the NH of Phe. In these structures, possible induced by an ionic interaction between the carboxylic group of Asp 32 and the NH group of the N‐terminal amino acid, the lateral chains of the various residues are quite distant from each other (15–16 Å). Under acidic conditions, extended structures without interactions between side chains predominate for CCK 5 and CCK 6 , while for CCK 4 , a conformational change drawing the Trp and Phe side chains in close proximity was shown by fluorescence. The conformations observed in aqueous medium at physiological pH are discussed in relation to the biological activity of these peptides.