【摘要】 合理设计一些容量小的、针对特定靶标的化合物库 (称为集中库 ,focused library) ,是当前组合库设计中的热点。当靶标的三维结构可以通过 X射线衍射或 NMR等手段确定后 ,人们就能采用几种不同的策略来进行组合库的设计。本文讨论了在靶标结合位点的约束下 ,进行组合库设计的主要方法及程序 ,同时强调了它们的优点与不足。通过这些方法的成功应用实例 ,显示了它们在新药创制中的广泛应用前景更多还原

【Abstract】 Currently, rational design of small focused libraries, which are biased toward specific therapeutic targets, is at the forefront of combinatorial library design. When the 3-D structure of the target is obtained through X-ray or NMR, various structure-based design strategies can be used in focused library design. In this paper, the major methods and programs specially developed for designing combinatorial libraries under the constraints of the binding site of a biological target and their advantages and disadvantages are reviewed. The examples of the successful application of these methodologies demonstrate their promotion to the drug discovery.更多还原