SYNTHESIS AND BIOLOGICAL-ACTIVITIES OF SOME HUMAN GASTRIN ANALOGS

The synthesis of analogs of the C-terminal tridecapeptide of gastrin i s described. These pseudopeptide analogs were obtained either by repla cing the C-terminal phenylalanine amide with 2-phenylethylalcohol or w ith 2-phenylethylamine, or by replacing the peptide bond between Trp a nd Leu, or between Leu and Asp with an aminomethylene (CH2NH). The abi lity of these compounds to stimulate gastric acid secretion in anesthe tized rats and to inhibit binding of labeled CCK-8 to isolated cells f rom rabbit fundic mucosa was tested. [desPhe(13), Leu(11)]-HG-12-I-bet a-phenylethylester 33, [desPhe(13), Leu(11)]-HG-12-II-beta-phenylethyl ester 38,[desPhe(13), Leu(11)]-HG-12-I-beta-phenylethylamide 32, and [ desPhe(13), Leu(11)]-HG-12-II-beta-phenylethylamide 37 acted as gastri n receptor antagonists, while [Trp (10)-Psi(CH2NH)-Leu(11)]-HG-13-I 31 and [Trp(10)-Psi(CH2NH)-Leu(11)]-HG-13-II 36 acted as agonists. Unexp ectedly, [Leu(11)-Psi(CH2NH)-Asp(12)]-HG-13-I 30 and [Leu(11)-Psi(CH2N H)-Asp(12)]-HG-13-II 35 were almost devoid of affinity for the gastrin receptor.