Brik Ashraf, Wu Chung-Yi, Wong Chi-Huey
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, USA.
Org Biomol Chem. 2006 Apr 21;4(8):1446-57. doi: 10.1039/b600055j. Epub 2006 Mar 22.
The use of libraries extracted from nature or constructed by combinatorial chemistry, have been widely appreciated in the drug discovery area. In this perspective, we present our contribution to the field of enzyme inhibitor discovery using a useful approach that allows diversification of a common core in a microtiter plate followed by in situ screening. Our method relies on an organic reaction that is highly selective, high yielding, amenable to the microscale and preferably can be performed in water. The core can be a designed molecule based on the structural and mechanistic information of the target, a compound with a weak binding affinity, or a natural product. Several reactions were found useful for this approach and were applied to the rapid discovery of potent inhibitors of representative enzymes.
从自然界提取或通过组合化学构建的文库在药物发现领域已得到广泛认可。从这个角度来看，我们展示了我们在酶抑制剂发现领域的贡献，采用了一种有用的方法，该方法允许在微量滴定板中对共同核心进行多样化，然后进行原位筛选。我们的方法依赖于一种有机反应，该反应具有高度选择性、高产率、适用于微尺度且最好能在水中进行。核心可以是基于靶标的结构和作用机制信息设计的分子、具有弱结合亲和力的化合物或天然产物。发现有几种反应适用于这种方法，并被应用于快速发现代表性酶的强效抑制剂。
