基于液相色谱-串联质谱技术鉴定药物靶标的研究进展

金金; 梁旭俊; 毕武; 张鹏飞

生命科学研究 ›› 2023, Vol. 27 ›› Issue (3) : 275 -282.

技术与应用

基于液相色谱-串联质谱技术鉴定药物靶标的研究进展

金金, 梁旭俊, 毕武, 张鹏飞

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Advances in the Identification of Drug Targets Based on Liquid Chromatography-Tandem Mass Spectrometry

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摘要

药物靶标是指细胞、组织或器官的特殊结构, 它能与药物相互作用, 促使药物发挥疗效。全面识别药物靶标对了解药物的作用机制及其潜在的副作用至关重要。目前, 应用广泛的药物靶标识别和鉴定技术, 如基于活性的蛋白质分析(activity-based protein profiling, ABPP)、以化合物为中心的化学蛋白质组学(compound-centric chemical proteomics, CCCP), 需要对化合物小分子进行修饰, 这可能会降低甚至改变药物分子的活性。因此, 无需对药物分子进行化学修饰的技术, 如药物亲和反应的靶标稳定(drug affinity responsive target stability, DARTS)、细胞热位移分析(cellular thermal shift assay, CETSA)和热蛋白质组分析(thermal proteome profiling, TPP), 逐渐成为药物靶标研究的重要手段。液相色谱-串联质谱技术是鉴定药物靶标蛋白的重要工具。本文综述了基于液相色谱-串联质谱技术的药物靶标研究方法的应用, 并对药物靶标鉴定技术的未来发展进行了展望。

Abstract

A drug target is a specific structure in a cell, tissue or organ that interacts with a drug to make it work. Comprehensive identification of drug targets is essential to understanding the mechanism of action of drugs and their potential side effects. Currently, widely used drug target identification and validation tech-niques, such as activity-based protein profiling (ABPP), compound-centric chemical proteomics (CCCP), re-quire the modification of small-molecule compounds, which may reduce or alter the activity of drug mole-cules. Therefore, advanced techniques that do not require chemical modification of drug molecules, such as drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and thermal proteome profiling (TPP), are becoming important tools for drug target research. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful tool for identification of drug target proteins. This paper reviewed drug target research techniques based on LC-MS/MS and future development of drug target identification.