Inhibition of Achromobacter protease I by lysinal derivatives.
Inhibition of Achromobacter protease I by lysinal derivatives.
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赖氨酸衍生物对无色杆菌蛋白酶 I 的抑制作用。
DOI：
10.1271/bbb.56.1604
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
M. Soejima
中科院分区：
文献类型：
--
作者：
T. Masaki;T. Tanaka;S. Tsunasawa;F. Sakiyama;M. Soejima
化学合成了Z-Val-、Z-Pro-、Z-Leu-Leu-、Z-Leu-Pro-lysinals和BZ-DL-lysinal，并测试了它们对赖氨酸专一性丝氨酸蛋白酶Achromobacter Protease I(API)的新型抑制作用。在所测试的赖氨酸衍生物中，Z-Val-lysinal是最有效的竞争性抑制剂，用Tos-Lys-ome进行的酯解试验估计其Ki为6.5 nM。在氨解试验中，Z-亮氨酸-赖氨酸是最有效的抑制剂，其抑制方式是非竞争性的。在酯解和氨解测定中，其他赖氨酸衍生物的KI均比亮氨酸低10(3)倍以上。缺乏醛基团的Z-Val-赖氨醇是一种竞争性较差的抑制剂。这些结果表明，酰基、酰氨基酰基和酰基肽基赖氨酸对Achromobacter Protein I具有过渡态抑制作用。
Z-Val-, Z-Pro-, Z-Leu-Leu-, and Z-Leu-Pro-lysinals and BZ-DL-lysinal were chemically synthesized and tested as novel inhibitors for Achromobacter protease I (API), a lysine-specific serine protease. Among the lysinal derivatives tested, Z-Val-lysinal was the most potent competitive inhibitor, its Ki being estimated as 6.5 nM in an esterolytic assay with Tos-Lys-OMe. In an amidolytic assay, Z-Leu-Leu-lysinal was the most potent inhibitor and the apparent mode of inhibition was non-competitive. The Kis of the other lysinal derivatives in both esterolytic and amidolytic assays were more than 10(3) times lower than that of leupeptin. Z-Val-lysinol, lacking the aldehyde group, was a poor competitive inhibitor. These results suggest that acyl-, acylaminoacyl-, and acylpeptidyllysinals function as a transition-state inhibitor for Achromobacter protease I.