ArticleAnalytical chemistry2023
Added Value of Internal Fragments for Top-Down Mass Spectrometry of Intact Monoclonal Antibodies and Antibody-Drug Conjugates.
Article in Analytical chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Gas-phase unfolding assay rapidly predicts structure-function relationships in engineered antibodies with tuned flexibilities.Nature communications · 2026Article
- Native Top-Down Mass Spectrometry Combined with High-Resolution Charge Variant Analysis of Trastuzumab Originator and Biosimilars.Journal of the American Society for Mass Spectrometry · 2026Article
- On the Utility of Infrared Photoactivation for Native Top-Down and Complex-Down Orbitrap Mass Spectrometry of Soluble Proteoform Complexes.Journal of the American Society for Mass Spectrometry · 2026Article
- Uncovering hidden protein modifications with native top-down mass spectrometry.Nature methods · 2025Article
- Top-Down and Middle-Down Mass Spectrometry of Antibodies.Molecular & cellular proteomics : MCP · 2025Review
- Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets.Frontiers in immunology · 2025Review
- Nanobodies: From High-Throughput Identification to Therapeutic Development.Molecular & cellular proteomics : MCP · 2024Review
- Enhanced Payload Localization in Antibody-Drug Conjugates Using a Middle-Down Mass Spectrometry Approach with Proton Transfer Charge Reduction.Analytical chemistry · 2024Article
- Characterization of a Monoclonal Antibody by Native and Denaturing Top-Down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2024Article
- Mass spectrometry-intensive top-down proteomics: an update on technology advancements and biomedical applications.Analytical methods : advancing methods and applications · 2024Review
- Panda-UV Unlocks Deeper Protein Characterization with Internal Fragments in Ultraviolet Photodissociation Mass Spectrometry.Analytical chemistry · 2024Article
- Endogenous monoclonal immunoglobulins analyzed using the EXENT® solution and LC-MS.Journal of mass spectrometry and advances in the clinical lab · 2024Article
- Internal Fragments Enhance Middle-Down Mass Spectrometry Structural Characterization of Monoclonal Antibodies and Antibody-Drug Conjugates.Analytical chemistry · 2024Article
- Top-down proteomics.Nature reviews. Methods primers · 2024Article
- Improved characterization of trastuzumab deruxtecan with PTCR and internal fragments implemented in middle-down MS workflows.Analytical and bioanalytical chemistry · 2024Article
- Detection of Lipid-Bound Bacteriorhodopsin Trimer Complex Directly from Purple Membrane by Native Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2023Article
- Mass spectrometry characterization of antibodies at the intact and subunit levels: from targeted to large-scale analysis.International journal of mass spectrometry · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) are two of the most important therapeutic drug classes that require extensive characterization, whereas their large size and structural complexity make them challenging to characterize and demand the use of advanced analytical methods. Top-down mass spectrometry (TD-MS) is an emerging technique that minimizes sample preparation and preserves endogenous post-translational modifications (PTMs); however, TD-MS of large proteins suffers from low fragmentation efficiency, limiting the sequence and structure information that can be obtained. Here, we show that including the assignment of internal fragments in native TD-MS of an intact mAb and an ADC can improve their molecular characterization. For the NIST mAb, internal fragments can access the sequence region constrained by disulfide bonds to increase the TD-MS sequence coverage to over 75%. Important PTM information, including intrachain disulfide connectivity and N-glycosylation sites, can be revealed after including internal fragments. For a heterogeneous lysine-linked ADC, we show that assigning internal fragments improves the identification of drug conjugation sites to achieve a coverage of 58% of all putative conjugation sites. This proof-of-principle study demonstrates the potential value of including internal fragments in native TD-MS of intact mAbs and ADCs, and this analytical strategy can be extended to bottom-up and middle-down MS approaches to achieve even more comprehensive characterization of important therapeutic molecules.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.