抗体类药物非聚糖翻译后修饰的LC-MS表征分析  

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

作　　者：俞海东 石莲花 金有训 韩荣勋[2] YU Hai-Dong;SHI Lian-Hua;JIN You-Xun;HAN Rong-Xun(National Institute of Metrology,Beijing 102200,China;College of Animal Sciences,Yangtze University,Jingzhou 434025,China;Shanghai Zhongqiao Vocational and Technical University,Shanghai 201514,China)

机构地区：[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

出　　处：《生命科学》2023年第6期769-778,共10页Chinese Bulletin of Life Sciences

基　　金：国家重点研发计划项目(2022YFC2009600)。

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。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.

关 键 词：抗体类药物 LC-MS 表征 翻译后修饰 

分 类 号：O657[理学—分析化学] Q53[理学—化学]