Pendleton R G, Gessner G, Horner E
Rorer Central Research, King of Prussia, Pennsylvania.
J Pharmacol Exp Ther. 1989 Jul;250(1):31-6.
The purpose of this study was to define in a systematic experimental manner the minimal amino acid domain(s) present in the angiotensin II molecule that are required for binding to, as well as activation of, its receptor at physiological concentrations. Although removal of the C-terminal phenylalanine residue markedly reduced affinity for the rabbit adrenal cortical receptor, sequential additions of amino acids beginning with phenylalanine did not result in a molecule with significant receptor affinity until the hexapeptide stage was reached. Similar receptor affinities were obtained with the other two possible 6 amino acid fragments in the molecule. None of the possible pentapeptide fragments were active, as was also the case with representative 4, 3 and 2 amino acid sequences. Of the three hexapeptides, only the one containing phenylalanine as the C-terminal amino acid displayed agonist activity on the rabbit aortic strip. The other two behaved as competitive antagonists. These results indicate that 6 amino acids constitute the minimal receptor binding domain present in the angiotensin II molecule and that phenylalanine is crucial at the C-terminus for activating the receptor.
本研究的目的是以系统的实验方式确定血管紧张素II分子中存在的、在生理浓度下与受体结合并激活受体所需的最小氨基酸结构域。虽然去除C末端苯丙氨酸残基会显著降低对兔肾上腺皮质受体的亲和力，但从苯丙氨酸开始依次添加氨基酸，直到达到六肽阶段才得到具有显著受体亲和力的分子。该分子中其他两个可能的六氨基酸片段也获得了相似的受体亲和力。所有可能的五肽片段均无活性，代表性的四、三、二氨基酸序列也是如此。在这三个六肽中，只有以苯丙氨酸作为C末端氨基酸的六肽对兔主动脉条显示出激动剂活性。另外两个表现为竞争性拮抗剂。这些结果表明，六个氨基酸构成了血管紧张素II分子中存在的最小受体结合结构域，并且苯丙氨酸在C末端对于激活受体至关重要。
