ArticleProtein science : a publication of the Protein Society2019
Quantitative collision-induced unfolding differentiates model antibody-drug conjugates.
Article in Protein science : a publication of the Protein Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Gas-phase unfolding assay rapidly predicts structure-function relationships in engineered antibodies with tuned flexibilities.Nature communications · 2026Article
- Determination of Thermochemical Barriers in Multiple-Collision-Induced Dissociation Experiments on Gas-Phase Protein Complexes.Journal of the American Chemical Society · 2025Article
- New Frontiers in ADC Analysis: Advances in Chromatography, Electrophoresis, and Mass Spectrometry.The AAPS journal · 2025Review
- Computed Vibrational Heat Capacities for Gas-Phase Biomolecular Ions.Journal of the American Society for Mass Spectrometry · 2025Article
- Emerging opportunities for intact and native protein analysis using chemical proteomics.Analytica chimica acta · 2025Review
- Modeling collisional kinetic energy damping, heating, and cooling of ions in mass spectrometers: a tutorial perspective.International journal of mass spectrometry · 2024Article
- Collision Induced Unfolding Enables the Quantitation of Isomass Biotherapeutics in Complex Biological Matrices.Journal of the American Society for Mass Spectrometry · 2023Article
- Ion Mobility Mass Spectrometry (IM-MS) for Structural Biology: Insights Gained by Measuring Mass, Charge, and Collision Cross Section.Chemical reviews · 2023Review
- Article
- Separation and Collision Cross Section Measurements of Protein Complexes Afforded by a Modular Drift Tube Coupled to an Orbitrap Mass Spectrometer.Analytical chemistry · 2022Article
- Mass Spectrometry Methods for Measuring Protein Stability.Chemical reviews · 2022Review
- Surface-induced Dissociation Mass Spectrometry as a Structural Biology Tool.Chemical reviews · 2022Review
- Direct-MS analysis of antibody-antigen complexes.Proteomics · 2021Article
- High-Throughput Multi-attribute Analysis of Antibody-Drug Conjugates Enabled by Trapped Ion Mobility Spectrometry and Top-Down Mass Spectrometry.Analytical chemistry · 2021Article
- State-of-the-Art Native Mass Spectrometry and Ion Mobility Methods to Monitor Homogeneous Site-Specific Antibody-Drug Conjugates Synthesis.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Rapid and Simultaneous Characterization of Drug Conjugation in Heavy and Light Chains of a Monoclonal Antibody Revealed by High-Resolution Ion Mobility Separations in SLIM.Analytical chemistry · 2020Article
- VHH characterization. Comparison of recombinant with chemically synthesized anti-HER2 VHH.Protein science : a publication of the Protein Society · 2019Article
- Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-drug conjugates (ADCs) are antibody-based therapeutics that have proven to be highly effective cancer treatment platforms. They are composed of monoclonal antibodies conjugated with highly potent drugs via chemical linkers. Compared to cysteine-targeted chemistries, conjugation at native lysine residues can lead to a higher degree of structural heterogeneity, and thus it is important to evaluate the impact of conjugation on antibody conformation. Here, we present a workflow involving native ion mobility (IM)-MS and gas-phase unfolding for the structural characterization of lysine-linked monoclonal antibody (mAb)-biotin conjugates. Following the determination of conjugation states via denaturing Liquid Chromatography-Mass Spectrometry (LC-MS) measurements, we performed both size exclusion chromatography (SEC) and native IM-MS measurements in order to compare the structures of biotinylated and unmodified IgG1 molecules. Hydrodynamic radii (Rh) and collision cross-sectional (CCS) values were insufficient to distinguish the conformational changes in these antibody-biotin conjugates owing to their flexible structures and limited instrument resolution. In contrast, collision induced unfolding (CIU) analyses were able to detect subtle structural and stability differences in the mAb upon biotin conjugation, exhibiting a sensitivity to mAb conjugation that exceeds native MS analysis alone. Destabilization of mAb-biotin conjugates was detected by both CIU and differential scanning calorimetry (DSC) data, suggesting a previously unknown correlation between the two measurement tools. We conclude by discussing the impact of IM-MS and CIU technologies on the future of ADC development pipelines.
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