Ruffner Heinz, Bauer Andreas, Bouwmeester Tewis
Cellzome AG, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Drug Discov Today. 2007 Sep;12(17-18):709-16. doi: 10.1016/j.drudis.2007.07.011. Epub 2007 Aug 28.
Systematic genome-wide and pathway-specific protein-protein interaction screens have generated a putative, organizing framework of the spatial interconnectivity of a large number of human proteins, including numerous therapeutically relevant disease-associated proteins. The intrinsic value for drug discovery is that these physical protein-protein interaction networks may contribute to a mechanistic understanding of the pathophysiology of disease and can aid in the identification and prioritization of tractable targets and generate hypotheses on how to best drug non-tractable, disease-associated targets. Here, we review the 'therapeutic potential' of the 1st generation sub-genome-scale human interaction networks and disease-associated protein networks generated by yeast two-hybrid screens and affinity purification-mass spectrometry approaches.
全基因组范围和特定通路的系统性蛋白质-蛋白质相互作用筛选，已生成了一个关于大量人类蛋白质空间互联性的推测性组织框架，其中包括众多与治疗相关的疾病关联蛋白。药物发现的内在价值在于，这些物理性蛋白质-蛋白质相互作用网络可能有助于从机制上理解疾病的病理生理学，并有助于识别和确定可处理的靶点并对其进行优先级排序，还能就如何最佳地作用于难以处理的疾病关联靶点提出假设。在此，我们综述了通过酵母双杂交筛选和亲和纯化-质谱方法生成的第一代亚基因组规模人类相互作用网络和疾病关联蛋白网络的“治疗潜力”。
