EFFICIENT INHIBITION OF HUMAN-LEUKOCYTE ELASTASE AND CATHEPSIN-G BY SACCHARIN DERIVATIVES
EFFICIENT INHIBITION OF HUMAN-LEUKOCYTE ELASTASE AND CATHEPSIN-G BY SACCHARIN DERIVATIVES
复制标题
DOI：
10.1021/jm00073a019
复制
发表时间：
1993-10-15
影响因子：
7.3
通讯作者：
MCCLENAHAN, JJ
中科院分区：
文献类型：
--
作者：
GROUTAS, WC;HOUSERARCHIELD, N;MCCLENAHAN, JJ
一系列糖精衍生物 I 已被合成并评估了其对人白细胞弹性蛋白酶和组织蛋白酶 G 的抑制活性。大多数化合物被发现是有效且时间依赖性的弹性蛋白酶抑制剂。发现失活的弹性蛋白酶在 24 小时后几乎完全恢复其活性（80-90% 活性），并且重新激活的半衰期在 12-15 小时之间。向完全失活的酶中添加羟胺导致酶活性快速且完全恢复。在生化和模型研究的基础上提出了初步的作用机制。
A series of saccharin derivatives I has been synthesized and evaluated for their inhibitory activity toward human leukocyte elastase and cathepsin G. Most of the compounds were found to be efficient and time-dependent inhibitors of elastase. Inactivated elastase was found to regain its activity almost fully after 24 h (80-90 % activity) and the half-lives of reactivation ranged between 12-15 h. Addition of hydroxylamine to fully-inactivated enzyme led to rapid and complete recovery of enzymatic activity. A tentative mechanism of action is proposed on the basis of biochemical and model studies.