Rodriguez M, Dubreuil P, Bali J P, Martinez J
J Med Chem. 1987 May;30(5):758-63. doi: 10.1021/jm00388a002.
The effects of partial retro-inverso modifications of selected peptide bonds of the N-terminal tetrapeptide of gastrin have been studied. In some of the synthesized compounds, the phenylalanyl residue has been replaced by the (R,S)-2-benzylmalonyl, 3-phenylpropionyl, benzylcarbamoyl, or benzyloxycarbonyl moieties. All pseudopeptides showed affinity for the gastrin receptor, in vitro, with potencies varying from IC50 = 10(-7) to IC50 = 10(-4) M. These compounds exhibited little or no activity on acid secretion in the anesthetized rat but were able to antagonize the action of gastrin. Among the most potent were Boc-Trp-Leu-gAsp-CO-CH2CH2C6H5 (20) (ED50 = 0.15 microM/kg), Boc-Trp-Leu-gAsp-m(R,S)Phe-NH2 (3) (ED50 = 0.15 microM/kg), and Boc-Trp-gLeu-D-Asp-m(R,S)Phe-NH2 (7) (ED50 = 0.3 microM/kg).
已对胃泌素N端四肽特定肽键的部分反转异构修饰的效果进行了研究。在一些合成化合物中，苯丙氨酰残基已被（R,S）-2-苄基丙二酰基、3-苯丙酰基、苄基氨基甲酰基或苄氧羰基部分取代。所有拟肽在体外均显示出对胃泌素受体的亲和力，其效价范围为IC50 = 10(-7)至IC50 = 10(-4) M。这些化合物对麻醉大鼠的胃酸分泌几乎没有或没有活性，但能够拮抗胃泌素的作用。其中最有效的是Boc-Trp-Leu-gAsp-CO-CH2CH2C6H5（20）（ED50 = 0.15 microM/kg）、Boc-Trp-Leu-gAsp-m（R,S）Phe-NH2（3）（ED50 = 0.15 microM/kg）和Boc-Trp-gLeu-D-Asp-m（R,S）Phe-NH2（7）（ED50 = 0.3 microM/kg）。
