Ion Mobility-Mass Spectrometry and Collision Induced Unfolding Reveal Linker-Payload Effects on Antibody-Drug Conjugate Higher-Order Structure and Stability

Bioconjugate Chemistry 2026

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Authors: Devin M. Makey, Marion H. Emmert, Hang Hu, Eli J. Larson, Emmanuel Appiah‐Amponsah, Erik L Regalado, Rodell C. Barrientos, Brandon T. Ruotolo
DOI: 10.1021/acs.bioconjchem.6c00018
Cited by: 1
References: 36

Abstract

) of the ADC was observed. Conjugation at interchain cysteine residues disrupted the HOS of the ADC to a greater extent compared to site-specific conjugates, as evidenced by higher root-mean-square deviation values. CIU data revealed differences in conformation and stability in ADCs with different DARs and different positional isomers with the same DAR. These findings demonstrate the utility of IM-MS and CIU as a high-throughput, information-rich assay for probing the HOS and stability of ADCs during their discovery and development.

Fields of Study & Subjects

HER2/EGFR in Cancer Research Phosphodiesterase function and regulation Estrogen and related hormone effects

Publication details

Journal / source
Bioconjugate Chemistry
Publisher
American Chemical Society (ACS)
Volume
37
Issue
5
Pages
942–949
Publication date
1 May 2026
Language
EN