...
首页> 外文期刊>Biochemistry >EPISELECTION - NOVEL K-I-SIMILAR-TO NANOMOLAR INHIBITORS OF SERINE PROTEASES SELECTED BY BINDING OR CHEMISTRY ON AN ENZYME SURFACE
【24h】

EPISELECTION - NOVEL K-I-SIMILAR-TO NANOMOLAR INHIBITORS OF SERINE PROTEASES SELECTED BY BINDING OR CHEMISTRY ON AN ENZYME SURFACE

机译:EPISELECT-通过在酶表面上结合或化学选择的丝氨酸蛋白酶新的K-I-类似物至分子抑制剂

获取原文
获取原文并翻译 | 示例
           

摘要

A novel class of mechanism-based inhibitors of the serine proteases is developed using epitaxial selection. Tripeptide boronates esterified by an alcohol or alcohols at the boron retain the tight binding to trypsin-like enzymes associated with transition-state analogs and incorporate additional groups that can be utilized for selectivity between proteases. Formed by reaction of a series of alcohols with the inhibitor boronate oxygen(s), the most structurally compatible alcohol-derivatized inhibitors are either selected by binding to the enzyme (epitaxial selection) or assembled by epitaxial reaction on the enzyme surface. Mass spectrometry of the derivatized boronates and X-ray crystallography of the complexes identify the chemical structures and the three-dimensional interactions of inhibitors generated. This scheme also engineers navel, potent (K-i similar to 7 nM), and more specific inhibitors of individual serine proteases, by derivitizations of compounds obtained by epitaxial selection. [References: 76]
机译:使用外延选择开发了新型的基于机制的丝氨酸蛋白酶抑制剂。在硼处被一种或多种醇酯化的三肽硼酸酯保留与过渡态类似物相关的胰蛋白酶样酶的紧密结合,并掺入可用于蛋白酶之间选择性的其他基团。通过一系列醇与抑制剂硼酸氧的反应形成,结构上最相容的醇衍生化抑制剂可以通过与酶结合来选择(外延选择),也可以通过在酶表面上的外延反应进行组装。衍生化的硼酸盐的质谱分析和配合物的X射线晶体学分析确定了所生成抑制剂的化学结构和三维相互作用。该方案还通过衍生化通过外延选择获得的化合物来工程化肚脐,强效的肚脐(K-i类似于7 nM)和更特异性的单个丝氨酸蛋白酶抑制剂。 [参考:76]

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号