针对金属蛋白酶家族的新型异羟肟酸文库：设计、平行合成与筛选
A library of novel hydroxamic acids targeting the metallo-protease family: design, parallel synthesis and screening.
作者信息
Flipo Marion, Beghyn Terence, Charton Julie, Leroux Virginie A, Deprez Benoit P, Deprez-Poulain Rebecca F
机构信息
Inserm, U761, University of Lille 2, Faculty of Pharmacy, Institut Pasteur Lille, "Biostructures and Drug Discovery" 3 rue du Pr Laguesse F-59006 Lille cedex, France.
出版信息
Bioorg Med Chem. 2007 Jan 1;15(1):63-76. doi: 10.1016/j.bmc.2006.10.010. Epub 2006 Oct 12.
We report here the design and parallel synthesis of 217 compounds based on a malonic-hydroxamic acid template. These compounds are obtained via a two-step solution-phase procedure. The set of diverse building-blocks used makes this strategy suitable for the search of inhibitors of various metallo-proteases and for the investigation of the biological role of new metallo-proteases. As a proof of concept, we screened this library on Neutral Aminopeptidase (APN; EC 3.4.11.2), the prototypal enzyme of the M1 family. Several submicromolar inhibitors were identified.
我们在此报告基于丙二酸异羟肟酸模板设计并平行合成的217种化合物。这些化合物通过两步溶液相程序获得。所使用的各种构建模块使该策略适用于寻找各种金属蛋白酶的抑制剂以及研究新型金属蛋白酶的生物学作用。作为概念验证，我们在中性氨肽酶（APN；EC 3.4.11.2）上筛选了该文库，APN是M1家族的原型酶。鉴定出了几种亚微摩尔级抑制剂。
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