Bigaud M, Hauss B, Schalk C, Jauch M F, D'Orchymont H
Marion Merrell Dow Research Institute, Strasbourg, France.
Fundam Clin Pharmacol. 1994;8(2):155-61. doi: 10.1111/j.1472-8206.1994.tb00792.x.
The structure activity relationship of phosphoramidon analogues was studied for their ability to reduce the hypertensive effect of exogenous proET-1, probably via inhibition of an endothelin converting enzyme activity (ECE). Results concerning in vivo ECE and in vitro thermolysin inhibitions were compared. In contrast to the phosphoryl group of phosphoramidon, which was found to be an absolute requirement, the rhamnose moiety was of very little importance for the inhibition of either enzyme. Furthermore, the tryptophan residue of phosphoramidon appeared to be particularly important for the ECE inhibition, whereas thermolysin inhibition seemed to depend greatly on the leucine residue. It is concluded that in vivo ECE and thermolysin differ in the way they recognise phosphoramidon. The existence of an hydrophobic pocket, specific for the recognition of the tryptophan residue of phosphoramidon, could be proposed for ECE.
研究了磷酰胺类似物的构效关系，以了解它们降低外源性proET-1高血压作用的能力，这可能是通过抑制内皮素转化酶活性（ECE）实现的。比较了体内ECE抑制和体外嗜热菌蛋白酶抑制的结果。与磷酰胺的磷酰基是绝对必需的相反，鼠李糖部分对这两种酶的抑制作用很小。此外，磷酰胺的色氨酸残基似乎对ECE抑制特别重要，而嗜热菌蛋白酶抑制似乎很大程度上取决于亮氨酸残基。得出的结论是，体内ECE和嗜热菌蛋白酶在识别磷酰胺的方式上有所不同。可以推测ECE存在一个疏水口袋，专门用于识别磷酰胺的色氨酸残基。
