快速开发出一种强效的光触发丝氨酸水解酶 RBBP9 抑制剂。
Rapid development of a potent photo-triggered inhibitor of the serine hydrolase RBBP9.
机构信息
Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
出版信息
Chembiochem. 2012 Sep 24;13(14):2082-93. doi: 10.1002/cbic.201200445. Epub 2012 Aug 20.
Abstract
The serine hydrolases constitute a large class of enzymes that play important roles in physiology. There is great interest in the development of potent and selective pharmacological inhibitors of these proteins. Traditional active-site inhibitors often have limited selectivity within this superfamily and are tedious and expensive to discover. Using the serine hydrolase RBBP9 as a model target, we designed a rapid and relatively inexpensive route to highly selective peptoid-based inhibitors that can be activated by visible light. This technology provides rapid access to photo-activated tool compounds capable of selectively blocking the function of particular serine hydrolases.
摘要
丝氨酸水解酶构成了一大类在生理学中发挥重要作用的酶。人们对开发这些蛋白质的有效且选择性的药理学抑制剂非常感兴趣。传统的活性位点抑制剂在这个超家族中通常选择性有限，并且发现它们既繁琐又昂贵。我们以丝氨酸水解酶 RBBP9 作为模型靶标，设计了一种快速且相对廉价的方法，用于合成基于肽的高选择性抑制剂，这些抑制剂可以被可见光激活。这项技术提供了快速获得光激活工具化合物的途径，这些化合物能够选择性地阻断特定丝氨酸水解酶的功能。
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