CIRCULAR-DICHROISM STUDY ON FULLY BIOACTIVE CCK-PEPTIDES OF INCREASING CHAIN-LENGTH

A CD conformational analysis has been performed on CCK-peptides elonga ted at the N-terminus in sequence mode beyond the naturally occurring CCK-8 up to the pentadecapeptide sequence. By extending N-terminally t he CCK-8 sequence an intramolecular salt bridge between the tyrosine-O -sulfate and the arginine guanido function is allowed to be establishe d. However, this intramolecular electrostatic interaction was not foun d to affect the bioactivities of the CCK-peptides indicating that indu ction of such salt bridge at the level of the ligand molecule does not prevent a similar interaction at receptor level by exchange of the co unterion partner. As expected for unconstrained short linear peptides the dichroic properties in aqueous solution were indicative of predomi nantly random coil structure. Conversely, in aqueous TFE the CD spectr a were consistent with the presence of gamma-type turns similarly to w hat has been observed under identical conditions for small size peptid es related to the homologuous gastrin hormone. In surfactant solutions the CCK-peptides were found to assume beta-type structures by inserti ng at least the C-terminal portion of the bioactive core into more hyd rophobic compartments of the surfactant micelles, whereas the hydrophi lic charged N-termini of the CCK-peptides of increasing chain length a re exposed to the water phase in random coil structures as suggested b y the CD spectra. This contrasts previous findings related to the homo loguous gastrin peptides, where identical CD spectra were recorded in aqueous TFE and in presence of micelles. This observation strongly sug gests that gastrin and CCK related peptides exhibit distinct conformat ional preferences, despite their high degree of sequence homology, and fully agrees with the ability of CCK to interact specifically with di fferent receptors.