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Conjugation site characterization of antibody-drug conjugates using electron-transfer/higher-energy collision dissociation (EThcD)

文献类型：期刊论文

作者Song, Yuanli1,3; Gao, Jing1; Meng, Qian1; Tang, Feng1,3; Wang, Yuqiu1; Zeng, Yue1,3; Huang, Wei1,3; Shao, Hong2; Zhou, Hu1,3
刊名ANALYTICA CHIMICA ACTA
出版日期2023-04-22
卷号1251页码:7
ISSN号0003-2670
关键词Antibody -drug conjugates EThcD Conjugation site Peptide mapping Quality control
DOI10.1016/j.aca.2023.340978
通讯作者Shao, Hong(shaohong@smda.sh.cn) ; Zhou, Hu(zhouhu@simm.ac.cn)
英文摘要Antibody-drug conjugates (ADCs) are formed by binding of cytotoxic drugs to monoclonal antibodies (mAbs) through chemical linkers. A comprehensive evaluation of the critical quality attributes (CQAs) of ADCs is vital for drug development but remains challenging owing to ADC structural heterogeneity than mAbs. Drug conjugation sites can considerably affect ADC properties, such as stability and pharmacokinetics, however, few studies have focused on method development in this area owing to technical challenges. Hybrid electron-transfer/higher-energy collision dissociation (EThcD) produces more fragment ions than conventional higher-energy collision dissociation (HCD) fragmentation, which aids in identifying and localizing post-translational modifications. Herein, we systematically employ EThcD to assess the fragmentation mode impact on conjugation site charac-terization for randomly conjugated and site-specific ADCs. EThcD generates more fragment ions in tandem mass spectrometry (MS/MS) spectra compared with HCD. Additional ions aid in pinpointing the correct conjugation sites that bear complex linker payload structures. Our study may contribute to the quality control of various preclinical and clinical ADCs.
WOS关键词ADO-TRASTUZUMAB EMTANSINE ; MASS-SPECTROMETRY ; STRUCTURAL-CHARACTERIZATION ; PROTEOMICS ; FRAGMENTATION ; HETEROGENEITY ; PERFORMANCE ; CHALLENGES ; STABILITY ; PROTEASES
资助项目National Key Research and Development Program of China[2020YFA0509000] ; Science and Technology Commission of Shanghai Municipality[20XD1424900] ; Shanghai Municipal Science and Technology Major Project ; Technology Innovation Project of Instrument and Equipment Function Development[2021-DK-02] ; Technical Support Talents Project of the Chinese Academy of Sciences ; open project of NMPA Key Laboratory of Quality Control of Therapeutic Monoclonal Antibodies ; [2022000017]
WOS研究方向Chemistry
语种英语
出版者ELSEVIER
WOS记录号WOS:000992928500001
源URL[http://119.78.100.183/handle/2S10ELR8/306650]  
专题新药研究国家重点实验室
通讯作者Shao, Hong; Zhou, Hu
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Media, Analyt Res Ctr Organ & Biol Mol, CAS Key Lab Receptor Res,State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Shanghai Inst Food & Drug Control, NMPA Key Lab Qual Control Therapeut Monoclonal Ant, 1500 Zhangheng Rd, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Song, Yuanli,Gao, Jing,Meng, Qian,et al. Conjugation site characterization of antibody-drug conjugates using electron-transfer/higher-energy collision dissociation (EThcD)[J]. ANALYTICA CHIMICA ACTA,2023,1251:7.
APA Song, Yuanli.,Gao, Jing.,Meng, Qian.,Tang, Feng.,Wang, Yuqiu.,...&Zhou, Hu.(2023).Conjugation site characterization of antibody-drug conjugates using electron-transfer/higher-energy collision dissociation (EThcD).ANALYTICA CHIMICA ACTA,1251,7.
MLA Song, Yuanli,et al."Conjugation site characterization of antibody-drug conjugates using electron-transfer/higher-energy collision dissociation (EThcD)".ANALYTICA CHIMICA ACTA 1251(2023):7.

入库方式： OAI收割

来源：上海药物研究所

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