Fletcher Steven, Hamilton Andrew D
Department of Chemistry, Yale University, PO Box 208107, New Haven, CT 06520-8107, USA.
J R Soc Interface. 2006 Apr 22;3(7):215-33. doi: 10.1098/rsif.2006.0115.
Protein-protein interactions play key roles in a range of biological processes, and are therefore important targets for the design of novel therapeutics. Unlike in the design of enzyme active site inhibitors, the disruption of protein-protein interactions is far more challenging, due to such factors as the large interfacial areas involved and the relatively flat and featureless topologies of these surfaces. Nevertheless, in spite of such challenges, there has been considerable progress in recent years. In this review, we discuss this progress in the context of mimicry of protein surfaces: targeting protein-protein interactions by rational design.
蛋白质-蛋白质相互作用在一系列生物过程中发挥着关键作用，因此是新型治疗药物设计的重要靶点。与酶活性位点抑制剂的设计不同，由于涉及的界面面积大以及这些表面相对平坦且无特征的拓扑结构等因素，破坏蛋白质-蛋白质相互作用要困难得多。然而，尽管存在这些挑战，近年来仍取得了相当大的进展。在本综述中，我们将在蛋白质表面模拟的背景下讨论这一进展：通过合理设计靶向蛋白质-蛋白质相互作用。
