title: Synthesis and biological activities of some human gastrin analogs.
abstract: The synthesis of analogs of the C-terminal tridecapeptide of gastrin is described. These pseudopeptide analogs were obtained either by replacing the C-terminal phenylalanine amide with 2-phenylethylalcohol or with 2-phenylethylamine, or by replacing the peptide bond between Trp and Leu, or between Leu and Asp with an aminomethylene (CH2NH). The ability of these compounds to stimulate gastric acid secretion in anesthetized rats and to inhibit binding of labeled CCK-8 to isolated cells from rabbit fundic mucosa was tested. [desPhe13, Leu11]-HG-12-I-beta-phenylethylester 33, [desPhe13, Leu11]-HG-12-II-beta-phenylethylester 38, [desPhe13, Leu11]-HG-12-I-beta-phenylethylamide 32, and [desPhe13, Leu11]-HG-12-II-beta-phenylethylamide 37 acted as gastrin receptor antagonists, while [Trp10-psi(CH2NH)-Leu11]-HG-13-I 31 and [Trp10-psi(CH2NH)-Leu11]-HG-13-II 36 acted as agonists. Unexpectedly, [Leu11-psi(CH2NH)-Asp12]-HG-13-I 30 and [Leu11-psi (CH2NH)-Asp12]-HG-13-II 35 were almost devoid of affinity for the gastrin receptor.
authors.affiliation: Laboratório de Tecnologia Químico Farmacêutica, Faculdade de Farmácia, Universidade Federal de Pernambuco, Recife, Brasil.
authors.forename: A C
authors.initials: AC
authors.lastname: Lima-Leite
authors.forename: P
authors.initials: P
authors.lastname: Fulcrand
authors.forename: J C
authors.initials: JC
authors.lastname: Galleyrand
authors.forename: G
authors.initials: G
authors.lastname: Berge
authors.forename: A
authors.initials: A
authors.lastname: Aumelas
authors.forename: J P
authors.initials: JP
authors.lastname: Bali
authors.forename: J
authors.initials: J
authors.lastname: Castel
authors.forename: J
authors.initials: J
authors.lastname: Martinez
mesh_terms: D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D010452:Peptide Biosynthesis; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors
chemical_list: D005755:Gastrins; D011949:Receptors, Cholecystokinin