Structure-activity relationships of CCK sub(26-33)-related analogues modified in position 33

In the sequence of the C-terminal octapeptide of cholecystokinin, the phenylalanine amide residue in position 33 is of primary importance for the biological activity. Indeed, removal of Phe super(33)-NH sub(2) is a modification known to induce antagonist properties. The influence of the chemical nature of the Phe-NH sub(2) side chain on the biological activity of CCK sub(8) was investigated through replacement of this residue by several amino acids with different lipophilic properties in the sequence of Boc(Nle super(28), Nle super(31))CCK sub(27-33), an equipotent analogue of CCK sub(8). The binding properties of these new CCK-related analogues: Boc(Nle super(31, X) super(3)3C)CK sub(27-33) were measured on both mouse brain and guinea pig pancreatic membranes, and their peripheral activities on amylase secretion and contractions of guinea pig ileum.