title: Synthesis and biological activity of 2-phenylethyl ester analogues of C-terminal heptapeptide of cholecystokinin modified in Trp 30 region.
abstract: We have tried to evaluate the significance of the tryptophan side chain residue and of the surrounding peptide bonds in the antagonist activity of cholecystokinin analogues lacking the C-terminal amide function and having a D-tryptophan. In order to perform this study, analogues of the C-terminal heptapeptide of cholecystokinin were synthesized by replacing the C-terminal phenylalanine residue with 2-phenylethyl alcohol and by either replacing the tryptophan residue with an alanine, a norleucine and a phenylalanine residue, or introducing a "reduced peptide bond" in the tryptophan 30 region. Most of these compounds were able to reproduce only part of the response of cholecystokinin in stimulating amylase release from rat pancreatic acini, as was already observed for 2-phenylethyl ester analogues of CCK. These results point out the key role of tryptophan 30 in the biological response of cholecystokinin.
authors.affiliation: CCIPE, Faculty of Pharmacy, Montpellier, France.
authors.forename: M
authors.initials: M
authors.lastname: Rolland
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez
authors.forename: M F
authors.initials: MF
authors.lastname: Lignon
authors.forename: M C
authors.initials: MC
authors.lastname: Galas
authors.forename: J
authors.initials: J
authors.lastname: Laur
authors.forename: A
authors.initials: A
authors.lastname: Aumelas
authors.forename: J
authors.initials: J
authors.lastname: Martinez
mesh_terms: D000595:Amino Acid Sequence; D000681:Amylases / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism*; D012844:Sincalide
chemical_list: D009842:Oligopeptides; D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; C025997:cholecystokinin (27-33); D000681:Amylases; D012844:Sincalide; D010626:Phenylethyl Alcohol