不可逆探针已被证明是研究药物受体药理学的结构和功能特征的有用药理学工具。已经证明它们对于分离和纯化受体特别有价值。此外,不可逆探针是识别和表征结合位点的有用工具,从而支持合理药物设计的推进。在这个Minireview中,我们提供了成功合成靶向G蛋白偶联受体(GPCRs)的不可逆探针的通用策略和指南.我们提供了常用的化学反应性和光反应性基团的概述,并对它们的性质和潜在应用进行了比较。此外,特别关注基于市售试剂引入这些反应性基团的合成方法。
Irreversible probes have been proven to be useful pharmacological tools in the study of structural and functional features in drug receptor pharmacology. They have been demonstrated to be particularly valuable for the isolation and purification of receptors. Furthermore, irreversible probes are helpful tools for the identification and characterization of binding sites, thereby supporting the advancement of rational drug design. In this Minireview, we provide insight into universal strategies and
guidelines to successfully synthesize irreversible probes that target G protein-coupled receptors (
GPCRs). We provide an overview of commonly used chemoreactive and photoreactive groups, and make a comparison of their properties and potential applications. Furthermore, there is a particular focus on synthetic approaches to introduce these reactive groups based on commercially available reagents.