Martinez J, Magous R, Lignon M F, Laur J, Castro B, Bali J P
J Med Chem. 1984 Dec;27(12):1597-601. doi: 10.1021/jm00378a012.
A series of C-terminal peptide segments of gastrin, i.e., (tert-butyloxycarbonyl)-L-tryptophyl-L-methionyl-L-aspartic acid amide, (tert-butyloxycarbonyl)-glycyl-L-tryptophyl-L-methionyl-L-aspartic acid amide, (tert-butyloxy-carbonyl)-L-tyrosyl-glycyl-L-tryptophyl-L-methionyl-L-asp artic acid amide, and (benzyloxycarbonyl)-L-glutamyl-L-alanyl-L-tyrosyl-glycyl-L-tryptophyl-L -methionyl-L-aspartic acid amide were prepared and were shown to competitively inhibit the binding of labeled human gastrin to its receptors in an isolated gastric mucosal cell preparation and to antagonize the action of gastrin on gastric acid secretion (ED50 from 1.5 to 7 mg/kg) in vivo in the reperfused rat stomach, determined according to the method of Ghosh and Schild. From these studies, it could be concluded that the C-terminal phenylalanine residue, which is of primary importance for intrinsic biological gastrin-like activity, is not essential for binding to gastrin receptors.
制备了一系列胃泌素的C末端肽段，即（叔丁氧羰基）-L-色氨酰-L-甲硫氨酰-L-天冬氨酸酰胺、（叔丁氧羰基）-甘氨酰-L-色氨酰-L-甲硫氨酰-L-天冬氨酸酰胺、（叔丁氧羰基）-L-酪氨酰-甘氨酰-L-色氨酰-L-甲硫氨酰-L-天冬氨酸酰胺，以及（苄氧羰基）-L-谷氨酰-L-丙氨酰-L-酪氨酰-甘氨酰-L-色氨酰-L-甲硫氨酰-L-天冬氨酸酰胺，结果表明，在分离的胃黏膜细胞制剂中，它们能竞争性抑制标记的人胃泌素与其受体的结合，并且在再灌注大鼠胃中，能在体内拮抗胃泌素对胃酸分泌的作用（半数有效剂量为1.5至7mg/kg），这是根据戈什和席尔德的方法测定的。从这些研究中可以得出结论，对于内在的胃泌素样生物活性至关重要的C末端苯丙氨酸残基，对于与胃泌素受体的结合并非必不可少。
