摘要
药物-靶蛋白相互作用研究是新药研发的重要环节,药物通过结合靶蛋白的特定氨基酸位点,从而影响靶蛋白的药理作用,这是药物发挥治疗效果的前提。目前,有多种技术应用于检测药物配体与靶蛋白相互作用。如基于热力学的细胞热转移分析(cellular thermal shift assay,CETSA)、差示扫描荧光(differential scanning fluorimetry,DSF)及质谱、核磁共振技术等。此外,高通量配体筛选技术为寻找靶蛋白特异性配体提供了技术便利,是高效鉴定药物配体与靶蛋白相互作用的利器。本文对药物小分子与靶点蛋白相互作用及亲和力技术进行了总结,并探讨了高通量配体筛选技术在药物研究的应用。
The interaction of drug and target protein is a critical part of new drug discovery.It is the premise for drugs to exert therapeutic effects by targeting specific binding sites of target proteins and thereby affecting its pharmacological activity.Currently,a variety of techniques are exploited to detect the interaction between drug ligands and target proteins.For example,cellular thermal shift assay(CETSA)and differential scanning fluorimetry(DSF)based on thermodynamics,mass spectrometry and nuclear magnetic resonance technology,etc.In addition,high-throughput ligand screening technology provides technical convenience for the search of specific ligand,and is a powerful tool to efficiently identify the interaction between drug ligand and target protein.Here,we summarize the detection techniques of interaction between small molecules and target proteins,and discuss the application of high-throughput ligand screening technology in drug research.
作者
董睿方
夏元铮
孔令义
DONG Rui-fang;XIA Yuan-zheng;KONG Ling-yi(Jiangsu Key Laboratory of Bioactive Natural Product Research,State Key Laboratory of Natural Medicines,School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 210009,China)
出处
《药学学报》
CAS
CSCD
北大核心
2023年第11期3242-3253,共12页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(81973524)。
关键词
靶蛋白
配体
亲和力
相互作用
高通量
target protein
ligand
affinity
interaction
high throughput
作者简介
通讯作者:夏元铮,Tel:13913024226,E-mail:xiayz@cpu.edu.cn;通讯作者:孔令义,Tel:86-25-83271405,E-mail:cpu_lykong@126.com。
