Michnick Stephen W, Ear Po Hien, Manderson Emily N, Remy Ingrid, Stefan Eduard
Département de Biochimie, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, Québec H3C 3J7, Canada.
Nat Rev Drug Discov. 2007 Jul;6(7):569-82. doi: 10.1038/nrd2311.
Changes in the interactions among proteins that participate in a biochemical pathway can reflect the immediate regulatory responses to intrinsic or extrinsic perturbations of the pathway. Thus, methods that allow for the direct detection of the dynamics of protein-protein interactions can be used to probe the effects of any perturbation on any pathway of interest. Here we describe experimental strategies - based on protein-fragment complementation assays (PCAs) - that can achieve this. PCA-based strategies can be used with or instead of traditional target-based drug discovery strategies to identify novel pathway-component proteins of therapeutic interest, to increase the quantity and quality of information about the actions of potential drugs, and to gain insight into the intricate networks that make up the molecular machinery of living cells.
参与生化途径的蛋白质之间相互作用的变化能够反映对该途径内在或外在扰动的即时调节反应。因此，能够直接检测蛋白质-蛋白质相互作用动态变化的方法可用于探究任何扰动对任何感兴趣途径的影响。在此，我们描述了基于蛋白质片段互补分析（PCA）的实验策略，这些策略能够实现这一点。基于PCA的策略可与传统的基于靶点的药物发现策略一起使用，或取而代之，以识别具有治疗意义的新型途径组成蛋白，增加有关潜在药物作用的信息数量和质量，并深入了解构成活细胞分子机制的复杂网络。
