酸性氨基酸硫醇衍生物对血管紧张素III形成的抑制作用。

Inhibition of angiotensin III formation by thiol derivatives of acidic amino acids.

作者信息

Wilk S, Thurston L S

机构信息

Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, NY 10029.

出版信息

Neuropeptides. 1990 Jul;16(3):163-8. doi: 10.1016/0143-4179(90)90129-m.

DOI:10.1016/0143-4179(90)90129-m

PMID:1982017

Abstract

Angiotensin III is formed by removal of the N-terminal Asp residue of angiotensin II in a reaction catalyzed by glutamyl aminopeptidase (aminopeptidase A EC 3.4.11.7). Thiol derivatives of glutamate and aspartate in which the alpha-COOH group was replaced by -CH2SH were synthesized as inhibitors of glutamyl aminopeptidase. Glutamate thiol was a potent inhibitor of glutamyl aminopeptidase (Ki = 4 x 10(-7) M) but even more potently inhibited microsomal alanyl aminopeptidase (Ki = 2.5 x 10(-7) M). Aspartate thiol (beta-homocysteine) was a less potent but more selective inhibitor of glutamyl aminopeptidase (glutamyl aminopeptidase: Ki = 1.2 x 10(-6) M; microsomal alanyl aminopeptidase: Ki = 7.5 x 10(-6) M). Neither compound inhibited cytosolic leucyl aminopeptidase. Aspartate thiol blocked the conversion of angiotensin II to angiotensin III. These derivatives are more selective than amastatin and may be of value in studies probing the biological significance of angiotensin III.

摘要

血管紧张素III是在谷氨酰氨肽酶（氨肽酶A，EC 3.4.11.7）催化的反应中，通过去除血管紧张素II的N端天冬氨酸残基而形成的。合成了α-COOH基团被-CH2SH取代的谷氨酸和天冬氨酸的硫醇衍生物，作为谷氨酰氨肽酶的抑制剂。谷氨酸硫醇是谷氨酰氨肽酶的有效抑制剂（Ki = 4×10^(-7) M），但更有效地抑制微粒体丙氨酰氨肽酶（Ki = 2.5×10^(-7) M）。天冬氨酸硫醇（β-高半胱氨酸）是谷氨酰氨肽酶的较弱但更具选择性的抑制剂（谷氨酰氨肽酶：Ki = 1.2×10^(-6) M；微粒体丙氨酰氨肽酶：Ki = 7.5×10^(-6) M）。这两种化合物均不抑制胞质亮氨酰氨肽酶。天冬氨酸硫醇阻断了血管紧张素II向血管紧张素III的转化。这些衍生物比氨肽菌素更具选择性，可能在探究血管紧张素III生物学意义的研究中具有价值。