Inhibitors of angiotensin-converting enzyme containing a tetrahedral arsenic atom.
Inhibitors of angiotensin-converting enzyme containing a tetrahedral arsenic atom.
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含有四面体砷原子的血管紧张素转换酶抑制剂。
DOI：
10.1042/bj2260447
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Kortylewicz,ZP
中科院分区：
文献类型：
--
作者：
Galardy,RE;Kortylewicz,ZP
研究了VA族和VIA族元素以及硅和硼的一系列四面体含氧酸作为血管紧张素转化酶抑制剂。砷酸盐是一种竞争性抑制剂，Ki为27 +/- 1 mM，比磷酸盐至少有效10倍。二甲基胂酸盐是一种竞争性抑制剂，Ki为70 +/- 9 mM，比二甲基次膦酸盐有效2倍。硼、硅、锑、硫和硒的含氧酸不是抑制剂。在这些结果的基础上，这种锌金属肽酶的强抑制底物类似物含有四面体磷原子，两个底物类似物含有四面体砷原子的制备。2-胂酰-L-脯氨酸是一种竞争性抑制剂，Ki为18 +/- 7 mM，比其磷类似物2-膦酰-L-脯氨酸弱2000倍以上。4-胂酸基-2-苄基丁酸是一种混合抑制剂，Ki为0.5 +/- 0.2 mM，与其磷类似物2-苄基-4-膦酰基丁酸的效力无法区分。
A series of tetrahedral oxo acids of Group VA and VIA elements and of silicon and boron were examined as inhibitors of angiotensin-converting enzyme. Arsenate is a competitive inhibitor with a Ki of 27 +/- 1 mM, at least 10-fold more potent than phosphate. Dimethylarsinate is a competitive inhibitor with a Ki of 70 +/- 9 mM, 2-fold more potent than dimethylphosphinate. Oxo acids of boron, silicon, antimony, sulphur and selenium are not inhibitors. On the basis of these results and the strong inhibition of this zinc metallopeptidase by substrate analogues containing a tetrahedral phosphorus atom, two substrate analogues containing a tetrahedral arsenic atom were prepared. 2-Arsonoacetyl-L-proline is a competitive inhibitor with a Ki of 18 +/- 7 mM, more than 2000-fold weaker than that of its phosphorus analogue 2-phosphonoacetyl-L-proline. 4-Arsono-2-benzylbutanoic acid is a mixed inhibitor with a Ki of 0.5 +/- 0.2 mM, indistinguishable in potency from its phosphorus analogue 2-benzyl-4-phosphonobutanoic acid.