McGill University, Department of Chemistry, Otto Maass Building, 801 Sherbrooke St. West, lab 206A, Montreal, QC, Canada, H3A 2K6.
Curr Top Med Chem. 2011;11(15):1944-55. doi: 10.2174/156802611796391212.
The potential areas of applications of chemogenomic approaches are very large. Thanks to the large amount of knowledge accumulated during years of research, it is now possible to consider the binding of a ligand to a protein in a much larger context. This knowledge combined with the augmentation of computing capabilities allows global approaches to investigate biological and pharmaceutical problems. Classification of proteins, focused libraries, selectivity profiles and elaboration of new ligands for orphan receptors can all be investigated using chemogenomic. G protein-coupled receptors (GPCRs) constitute a large protein family of significant interest in pharmaceutical research. Despite this interest, and excluding the more than 360 nonolfatory proteins, the endogenous ligands of about 100 GPCRs have still not been identified. The main limitation of GPCRs investigation is the lack of 3D structures. The goal of this review is to present different chemogenomic approaches that can be applied to GPCRs. Three types of such approaches are presented: ligand centered, protein centered and protein-ligand centered approaches. For each of them, current limitations and biases are mentioned.
化学生物基因组学方法的潜在应用领域非常广泛。由于多年研究中积累了大量的知识，现在可以在更大的范围内考虑配体与蛋白质的结合。这方面的知识与计算能力的提高相结合，使得可以采用全局方法来研究生物和制药问题。利用化学生物基因组学可以对蛋白质进行分类、设计靶向特定蛋白质的药物库、研究选择性特征以及开发针对孤儿受体的新配体。G 蛋白偶联受体（GPCR）是一个重要的蛋白质家族，在药物研究中具有重要意义。尽管如此，除了 360 多种非嗅觉蛋白外，仍有大约 100 种 GPCR 的内源性配体尚未被鉴定。GPCR 研究的主要限制是缺乏 3D 结构。本文的目的是介绍可应用于 GPCR 的不同化学生物基因组学方法。介绍了三种类型的此类方法：配体中心、蛋白质中心和蛋白质-配体中心方法。对于每一种方法，都提到了当前的局限性和偏见。
