摘要
中药发挥其临床功效必然有其物质基础,这些功效物质不仅是中药发挥药理活性的基石,亦是创新药物研发的重要源泉。但长期以来,中药效应物质的作用靶标不明、互作模式和药理机制不清,严重阻碍了中药的临床精准应用和国际化进程。近年来,随着生物质谱技术的不断革新,以质谱技术为核心的化学生物学和生命组学等前沿技术蓬勃发展,极大地助力了中药效应物质的作用靶标鉴定和药理机制解析。本文围绕中药效应物质靶标鉴定以及小分子-靶蛋白互作模式表征领域的国内外新近研究进展,着重阐述了基于生物质谱技术的小分子标记与非标记靶标发现两大策略的基本原理,并对其技术要点和应用领域进行了细致分析。此外,本文还重点介绍了近年来国内外学者借助生物质谱技术和多种前沿技术,在中药效应物质-靶蛋白互作模式表征方面取得的研究进展。相关研究策略、方法学和应用案例有望为中药效应物质的靶标发现和药理机制的深度解析等提供系列解决方案和研究示范。
The clinical efficacy of Chinese medicines(CMs)fundamentally relies on their material basis,with active constituents serving not only as the cornerstone of CM's pharmacological activity,but also as a valuable resource for innovative drug research and development.However,the precise clinical application and internationalization of CMs have long been hindered by limited understanding of the molecular targets,modes of action,and pharmacological mechanisms underlying their functional components.Novel biochemical and biophysical approaches,in combination with recent advancements in mass spectrometry(MS)-based techniques,instrumentation,and data analysis pipelines,have significantly facilitated the identification of molecular targets and elucidation of pharmacological mechanisms of functional components in CMs.This review summarizes recent advances in the target identification of functional components in CMs and the characterization of small moleculetarget protein interactions.We discuss the principles and technical aspects of small molecule-labeled and label-free target deconvoluted strategies leveraging biological mass spectrometry,providing a comparative analysis of their application scopes,strengths and limitations.This review article also addressed the recent progress made by the scholars in characterizing the interaction modes between functional components of CMs and target proteins,using biomass spectrometry and other cutting-edge technologies.The relevant research strategies,methodologies,and application cases are expected to provide a series of solutions and research models for the discovery of targets and in-depth elucidation of pharmacological mechanisms of CMs pharmacodynamic substances.
作者
胡雪艳
褚夏燕
涂东珠
曾海荣
田甜
庄小禹
葛广波
HU Xue-yan;CHU Xia-yan;TU Dong-zhu;ZENG Hai-rong;TIAN Tian;ZHUANG Xiao-yu;GE Guang-bo(Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Experiment Center for Science and Technology,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine,Shanghai 201203,China)
出处
《药学学报》
北大核心
2026年第1期58-74,共17页
Acta Pharmaceutica Sinica
基金
国家重点研发计划“中医药现代化研究”重点专项(2022YFC3502000)
CYP3A4共价抑制剂的高效发现及作用模式表征新体系的构建及其应用(82273897)。
关键词
生物质谱
中药效应物质
靶标发现
作用模式表征
蛋白质组学
biological mass spectrometry
functional components of Chinese medicine
target identification
characterization of mode of action
proteomics
