Yin Hang, Hamilton Andrew D
Yale University, New Haven, CT, USA.
Angew Chem Int Ed Engl. 2005 Jul 4;44(27):4130-63. doi: 10.1002/anie.200461786.
The development of small-molecule modulators of protein-protein interactions is a formidable goal, albeit one that possesses significant potential for the discovery of novel therapeutics. Despite the daunting challenges, a variety of examples exists for the inhibition of two large protein partners with low-molecular-weight ligands. This review discusses the strategies for targeting protein-protein interactions and the state of the art in the rational design of molecules that mimic the structures and functions of their natural targets.
开发蛋白质-蛋白质相互作用的小分子调节剂是一个艰巨的目标,尽管这一目标在发现新型治疗药物方面具有巨大潜力。尽管面临巨大挑战,但已有多种利用低分子量配体抑制两个大型蛋白质相互作用伙伴的实例。本文综述了针对蛋白质-蛋白质相互作用的策略以及在合理设计模拟天然靶点结构和功能的分子方面的最新进展。