发展亲和质谱技术加速G蛋白偶联受体的配体筛选和药物发现

基于靶蛋白 配体亲合作用检测的亲和质谱技术与常规高通量筛选技术相辅相成，已发展成为药物先导化合物早期发现流程中的关键技术之一。G蛋白偶联受体（GPCR）家族由于其特殊的生化性质，对基于亲合作用的配体筛选和配体表征提出了巨大的技术挑战。文章主要介绍亲和质谱技术用于GPCR配体筛选的基本原理及其特点，并总结该技术用于大规模化合物库及天然草本粗提物筛选的前沿进展。

Developing the affinity mass spectrometry technology for the discovery of chemicalligands and drug leads towards GPCR targets

Affinity mass spectrometry (affinity MS) based on the detection of protein target-ligand interaction is a powerful technologycomplementary to conventional high-throughput screening (HTS) assays and has been successfully incorporated into the early-phaselead discovery pipeline. Owing to the special biochemical properties of G protein-coupled receptors (GPCRs), tremendous technicalchallenges are posed to affinity MS-based ligand screening for GPCR targets. Here we briefly summarize the principle and features ofthe affinity MS technique adapted to GPCR ligand screening, and review the recent progress in screening both large-scale compoundlibraries and natural herb extracts with affinity MS for discovery of unreported GPCR ligands and modulators.