From purified GPCRs to drug discovery: the promise of protein-based methodologies
From purified GPCRs to drug discovery: the promise of protein-based methodologies
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DOI：
10.1016/j.coph.2009.04.002
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发表时间：
2009-10-01
影响因子：
4
通讯作者：
Wagner, Renaud
中科院分区：
文献类型：
--
作者：
Alkhalfioui, Fatima;Magnin, Thierry;Wagner, Renaud
G蛋白偶联受体（GPCR）是最大的膜蛋白家族，是许多疾病的理想治疗靶点。除了基于细胞的测定和高通量筛选（HTS）之外，并且由于毫克量的活性纯化受体的可用性，专注于可溶性GPCR的基于蛋白质的方法正在越来越多地用于这种药物发现努力。沿着GPCR结构的开发，创新的生物化学和生物物理学方法为改进结构-活性关系的知识、鉴定新的相互作用伴侣和确定不同模型环境中的受体行为开辟了新的途径。这篇综述总结了最先进的方法，强大的生产和纯化的可溶性和活性GPCR，以及最近已经获得的主要成果，在GPCR生物学使用的面板，这样的蛋白质为基础的方法。
G-protein-coupled receptors (GPCRs), the largest family of membrane proteins, represent ideal therapeutic targets for a number of disorders and diseases. Besides cell-based assays and high throughput screening (HTS), and thanks to the availability of milligram quantities of active purified receptors, protein-based approaches focusing on soluble GPCRs are growingly being used in this drug discovery effort. Along with the exploitation of GPCRs structures, innovative biochemical and biophysical approaches open up new routes for improving the knowledge of structure-activity relationships, for the identification of novel interacting partners and for the determination of receptor behaviour in different model environments. This review summarizes the state-of-the-art methodologies that robustly allow for the production and purification of soluble and active GPCRs, as well as the main outcomes that have been recently gained in GPCR biology using a panel of such protein-based approaches.