Circular dichroism study on fully bioactive CCK-peptides of increasing chain length

A CD conformational analysis has been performed on CCK-peptides elongated at the N-terminus in sequence mode beyond the naturally occurring CCK-8 up to the pentadecapeptide sequence. By extending N-terminally the CCK-8 sequence an intramolecular salt bridge between the tyrosine-O-sulfate and the arginine guanido function is allowed to be established. However, this intramolecular electrostatic interaction was not found to affect the bioactivities of the CCK-peptides indicating that induction of such salt bridge at the level of the ligand molecule does not prevent a similar interaction at receptor level by exchange of the counterion partner. As expected for unconstrained short linear peptides the dichroic properties in aqueous solution were indicative of predominantly random coil structure. Conversely, in aqueous TFE the CD spectra were consistent with the presence of γ-type turns similarly to what has been observed under identical conditions for small size peptides related to the homologuous gastrin hormone. In surfactant solutions the CCK-peptides were found to assume β-type structures by inserting at least the C-terminal portion of the bioactive core into more hydrophobic compartments of the surfactant micelles, whereas the hydrophilic charged N-termini of the CCK-peptides of increasing chain length are exposed to the water phase in random coil structures as suggested by the CD spectra. This contrasts previous findings related to the homologuous gastrin peptides, where identical CD spectra were recorded in aqueous TFE and in presence of micelles. This observation strongly suggests that gastrin and CCK related peptides exhibit distinct conformational preferences, despite their high degree of sequence homology, and fully agrees with the ability of CCK to interact specifically with different receptors. © 1993, Walter de Gruyter. All rights reserved.SCOPUS: ar.j