氢氘交换质谱技术在蛋白质类药物研究领域的应用

Application of Hydrogen-Deuterium Exchange Mass Spectrometry Technology in the Field of Protein Drug Research

随着生物医药技术的发展,蛋白质作为药物研究中的主要靶点或治疗制剂,逐渐应用于临床各种适应症。而研究蛋白质的结构变化对理解候选药物的作用方式及功能至关重要,因此在蛋白质类药物设计及生产过程中往往需要进行高级结构(HOS)表征、抗原表位作图、构象变化及动力学等研究。氢氘交换质谱(HDX-MS)技术作为一种高灵敏,快速,高通量的蛋白质结构动力学表征技术,由于其对大分子蛋白构象表征的优势,逐步发展成为药物研发特别是蛋白质类药物设计和生物治疗学研究的重要工具。本文详细介绍了HDX-MS技术的发展历史及基本原理,并对该技术在蛋白质类药物研发领域的研究进展进行了系统回顾与展望。

With the development of biomedical technology,as the main target or therapeutic agent in drug research,protein is gradually used in various clinical indications.Studying the proteins structural changes is critical to understand the action and function mode of candidate drugs.Therefore,in the design and production of protein drugs,it is often necessary to carry out studies on higher-order structure (HOS) characterization,epitope mapping,conformational changes and kinetics.Hydrogen-deuterium exchange mass spectrometry (HDX-MS) is a highly sensitive,fast,and high-throughput protein structure dynamic characterization technology.Due to its advantages in the conformational characterization of macromolecular proteins,it has gradually developed into an important tool for drug development,especially in protein drug design and biotherapeutics research.This article introduces the development history and basic principles of HDX-MS technology in detail,and the research progress of this technology in the field of protein drug development is reviewed and prospected.