摘要
鉴定小分子药物的靶蛋白对于理解药物的作用机理以及药物副作用至关重要。传统方法需要对药物进行化学修饰共价交联,可能会导致药物活性的改变。目前已经发展多种无需化学修饰便可以对药物靶蛋白鉴定的方法,包括药物亲和力反应靶标稳定性技术(Drug affinity responsive target stability,DARTS)、蛋白质氧化速率稳定性技术(Stability of proteins from rates of oxidation,SPROX)、细胞热移位分析技术(Cellular thermal shift assay,CETSA)和热蛋白组分析技术(Thermal proteome profiling,TPP)等。文中将介绍这些技术的原理、应用以及各自的优点和局限性,另外也介绍了这些技术最新的优化方案。
Identification of the target proteins of small molecule drugs is crucial for understanding the mechanisms of drug actions and its side effects. Conventional methods require chemical modification, which might alter the activities of the drugs. Various label-free techniques have been developed to identify drug target proteins without chemical modifications. This includes drug affinity responsive target stability(DARTS), stability of proteins from rates of oxidation(SPROX), cellular thermal shift assay(CETSA), thermal proteome profiling(TPP) and many others. Here we review the principles and applications of these label-free techniques, their advantages and limitations, as well as the most recent advances.
作者
马婕
刘强
Jie Ma;Qiang Liu(Department of Histoembryology,Genetics and Developmental Biology,Basic Medical College,Shanghai Key Laboratory of Reproductive Medicine,Shanghai Jiaotong University School of Medicine,Shanghai 200025,China)
出处
《生物工程学报》
CAS
CSCD
北大核心
2021年第4期1131-1138,共8页
Chinese Journal of Biotechnology
基金
国家自然科学基金(Nos.81571488,81771637)资助。
关键词
小分子药物
无共价修饰
药物亲和力反应靶标稳定性
蛋白质氧化速率稳定性
细胞热移位分析
热蛋白质组分析
small molecule drugs
label-free
drug affinity responsive target stability
stability of proteins from rates of oxidation
cellular thermal shift assay
thermal proteome profiling
