Chemical-biology approaches to pathway selective adenosine receptor ligands

该项目旨在开发新的化学生物学工具和方法，用于选择性靶向G蛋白偶联受体（GPCR）介导的信号通路。GPCR是一个重要的细胞表面信号蛋白家族，负责调节许多重要的生理功能。A1腺苷受体是一个重要的模型和治疗相关的GPCR，将是这个项目的重点。被称为双位配体的化合物，其可以与不同的结合位点（称为正构和变构位点）相互作用，将被探索作为能够激活信号传导途径的途径选择性试剂，所述信号传导途径介导期望的效果，而不是产生不良作用的那些。长期的益处包括鉴定具有更有选择性的作用模式和改善的安全性的生物活性化合物。

This project aims to develop new chemical-biology tools and approaches for selectively targeting signalling pathways mediated by G protein-coupled receptors (GPCR). GPCRs are an important family of cell surface signalling proteins that are responsible for the regulation of numerous vital physiological functions. The A1 adenosine receptor is an important model and therapeutically relevant GPCR that will be the focus of this project. Compounds known as bitopic ligands, which can interact with distinct binding sites (termed orthosteric and allosteric sites), will be explored as pathway selective agents capable of activating the signalling pathways mediating the desired effect in preference to those producing adverse effects. Longer-term benefits include the identification of bioactive compounds with more selective modes of action and improved safety profiles.