PXD040111

PXD040111 is an original dataset announced via ProteomeXchange.

Title	Conjugation site characterization of antibody–drug conjugates using electron-transfer/higher-energy collision dissociation (EThcD)
Description	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 high collision dissociation (HCD) fragmentation, which aid in identifying and localizing post-translational modifications (PTMs). Herein, we systematically employ EThcD to assess the fragmentation mode impact on conjugation site characterization 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.
HostingRepository	iProX
AnnounceDate	2023-02-14
AnnouncementXML	Submission_2023-03-26_23:20:18.781.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuanli Song
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-13 22:26:17	ID requested
1	2023-02-13 22:26:31	announced
⏵ 2	2023-03-26 23:20:20	announced	2023-03-27: Update publication information.

Song Y, Gao J, Meng Q, Tang F, Wang Y, Zeng Y, Huang W, Shao H, Zhou H, Conjugation site characterization of antibody-drug conjugates using electron-transfer/higher-energy collision dissociation (EThcD). Anal Chim Acta, 1251():340978(2023) [pubmed]

submitter keyword: Antibody–drug conjugates, EThcD, conjugation site, peptide mapping, quality control

Hu Zhou
contact affiliation	Shanghai Institute of Materia Medica, Chinese Academy of Sciences
contact email	zhouhu@simm.ac.cn
lab head
Yuanli Song
contact affiliation	Shanghai Institute of Materia Medica, Chinese Academy of Sciences
contact email	s20-songyuanli@simm.ac.cn
dataset submitter

iProX dataset URI