Wise Alan, Jupe Steven C, Rees Stephen
7TMR Systems Research Europe, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Herts SG1 2NY, United Kingdom.
Annu Rev Pharmacol Toxicol. 2004;44:43-66. doi: 10.1146/annurev.pharmtox.44.101802.121419.
The completion of the human genome sequencing project has identified approximately 720 genes that belong to the G-protein coupled receptor (GPCR) superfamily. Approximately half of these genes are thought to encode sensory receptors. Of the remaining 360 receptors, the natural ligand has been identified for approximately 210 receptors, leaving 150 so-called orphan GPCRs with no known ligand or function. The identification of ligands active at orphan GPCRs has been achieved through the development of a number of experimental approaches, including the screening of putative small molecule and peptide ligands, reverse pharmacology, and the use of bioinformatics to predict candidate ligands. In this review, we discuss the methodologies developed for the identification of ligands at orphan GPCRs and include examples of their successful application.
人类基因组测序项目的完成已鉴定出约720个属于G蛋白偶联受体（GPCR）超家族的基因。这些基因中约一半被认为编码感觉受体。在其余360种受体中，已为约210种受体鉴定出天然配体，剩下150种所谓的孤儿GPCR，其配体和功能均未知。通过开发多种实验方法已实现了对孤儿GPCR有活性的配体的鉴定，这些方法包括筛选假定的小分子和肽配体、反向药理学以及使用生物信息学预测候选配体。在本综述中，我们讨论了为鉴定孤儿GPCR的配体而开发的方法，并列举了其成功应用的实例。
