Analogues of cholecystokinin methylated in the side chain of carboxyterminal phenylalanine

Abstract

In the course of our study on cholecystokinin (CCK) a series of Boc-CCK-7 was synthesized. Their carboxyterminal part was modified by phenylalanine derivatives containing 2 or 4 and 2,6 or 2,4,6 methylated aromatic side-chain. During the synthesis, the racemic phenylalanine derivatives were used and peptides containing either L- or D- methylated phenylalanine were separated using a preparative HPLC. Gall bladder contraction, anorectic, sedative and analgetic bioassays of these analogues revealed that all of them behaved as CCK-8 agonists. While the analogues containing L-form of the methylated phenylalanines had almost the same potency (80% - 130%) in comparison to CCK-8, the presence of the D-form decreased the biological activity of corresponding analogues to 8 – 62% of the CCK-8 potency. These results are in agreement with the suggestion that phenylalanine residue in C-terminus takes part in biological activity transduction only.