Dualsystems Biotech AG, Grabenstrasse 11a, 8952 Schlieren, Switzerland.
Methods. 2012 Aug;57(4):423-9. doi: 10.1016/j.ymeth.2012.06.006. Epub 2012 Jun 19.
The majority of small molecule drugs act on protein targets to exert a therapeutic function. It has become apparent in recent years that many small molecule drugs act on more than one particular target and consequently, approaches which profile drugs to uncover their target binding spectrum have become increasingly important. Classical yeast two-hybrid systems have mainly been used to discover and characterize protein-protein interactions, but recent modifications and improvements have opened up new routes towards screening for small molecule-protein interactions. Such yeast "n"-hybrid systems hold great promise for the development of drugs which interfere with protein-protein interactions and for the discovery of drug-target interactions. In this review, we discuss several yeast two-hybrid based approaches with applications in drug discovery and describe a protocol for yeast three-hybrid screening of small molecules to identify their direct targets.
大多数小分子药物通过作用于蛋白质靶标来发挥治疗功能。近年来，人们已经清楚地认识到，许多小分子药物会作用于不止一个特定的靶标，因此，对药物进行分析以揭示其靶标结合谱的方法变得越来越重要。经典的酵母双杂交系统主要用于发现和表征蛋白质-蛋白质相互作用，但最近的改进和完善为筛选小分子-蛋白质相互作用开辟了新途径。这种酵母“n”杂交系统为开发干扰蛋白质-蛋白质相互作用的药物和发现药物-靶标相互作用提供了巨大的前景。在这篇综述中，我们讨论了几种基于酵母双杂交的方法在药物发现中的应用，并描述了一种使用酵母三杂交筛选小分子以鉴定其直接靶标的方案。
