《生命科学》 2023, 35(6): 769-778

抗体类药物非聚糖翻译后修饰的LC-MS表征分析

俞海东³ , 石莲花¹ , 金有训^1,* , 韩荣勋²

¹中国计量科学研究院，北京 102200 ²长江大学动物科学学院，荆州 434025 ³上海中侨职业技术大学，上海 201514

摘　要：

抗体类药物往往存在复杂多样的翻译后修饰(post-translational modifications, PTMs)，由此产生高度的异质性。PTMs 表征是抗体类药物研发的重要组成部分。尤其在早期研发阶段，高质量的结构表征可以为药物筛选、药物发现、工艺开发和优化提供指引和依据。基于液相色谱- 质谱联用(LC-MS) 技术的表征分析手段可快速、准确地识别PTMs，已成为抗体类药物PTMs 分析及结构表征的有力工具。该文综述了抗体类药物非聚糖PTMs 的鉴定成果，内容包括修饰类型、修饰位点、修饰所在区域、表达系统信息及潜在影响，并对LC-MS 表征分析策略进行了一定的探讨，希望为抗体类药物早期研发阶段的表征分析提供参考。综述的非聚糖PTMs 均通过LC-MS 或LC-MS/MS 技术得到了鉴定。

通讯作者：金有训 , Email:jinyx@nim.ac.cn

LC-MS characterization of non-glycan PTMs of antibody-based drugs

YU Hai-Dong³ , SHI Lian-Hua¹ , JIN You-Xun^1,* , HAN Rong-Xun²

¹National Institute of Metrology, Beijing 102200, China ²College of Animal Sciences, Yangtze University, Jingzhou 434025, China ³Shanghai Zhongqiao Vocational and Technical University, Shanghai 201514, China

Abstract:

Antibody-based drugs often show high heterogeneity due to complex and diverse post-translational modifications (PTMs). As an important support for drug development, characterization of PTMs can provide guidance and reference for drug screening, drug discovery, process development and optimization. LC-MS has become a powerful tool for identification and characterization of PTMs, due to the advantages of rapidness and high accuracy. Here we provide an overview of identification results of non-glycan PTMs of antibody-based drugs, including modification types, modified sites, located regions, expression systems and the resultant potential effects. Also, LC-MS based analytical strategies for characterization are discussed. We hope this paper can provide references for characterization of antibody-based drugs in the early development. PTMs reviewed in this paper were all identified by LC-MS or LC-MS/MS.

Communication Author：JIN You-Xun , Email:jinyx@nim.ac.cn