ArticlemAbs
In-depth qualitative and quantitative analysis of composite glycosylation profiles and other micro-heterogeneity on intact monoclonal antibodies by high-resolution native mass spectrometry using a modified Orbitrap.
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Who cites it
33 citing papers in PubMed.
- Characterizing Monoclonal Antibody Aggregation Using Charge Detection Mass Spectrometry and Industry Standard Methods.Journal of the American Society for Mass Spectrometry · 2025Article
- Assessment of monoclonal antibody glycosylation: a comparative study using HRMS, NMR, and HILIC-FLD.Analytical and bioanalytical chemistry · 2024Article
- A Critical Analysis of the FDA's Omics-Driven Pharmacodynamic Biomarkers to Establish Biosimilarity.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Approaches to Heterogeneity in Native Mass Spectrometry.Chemical reviews · 2022Review
- High-Resolution Native Mass Spectrometry.Chemical reviews · 2022Review
- Towards middle-up analysis of polyclonal antibodies: subclass-specific N-glycosylation profiling of murine immunoglobulin G (IgG) by means of HPLC-MS.Scientific reports · 2020Article
- Article
- Structural Analysis of Monoclonal Antibodies by Ultrahigh Resolution MALDI In-Source Decay FT-ICR Mass Spectrometry.Analytical chemistry · 2019Article
- N-glycan microheterogeneity regulates interactions of plasma proteins.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Comprehensive Proteoform Characterization of Plasma Complement Component C8αβγ by Hybrid Mass Spectrometry Approaches.Journal of the American Society for Mass Spectrometry · 2018Article
- Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S.Nature communications · 2018Article
- Native mass spectrometry combined with enzymatic dissection unravels glycoform heterogeneity of biopharmaceuticals.Nature communications · 2018Article
- Serum glycosylation characterization of osteonecrosis of the femoral head by mass spectrometry.European journal of mass spectrometry (Chichester, England) · 2018Article
- Global N-Glycan Site Occupancy of HIV-1 gp120 by Metabolic Engineering and High-Resolution Intact Mass Spectrometry.ACS chemical biology · 2017Article
- Direct analysis of aberrant glycosylation on haptoglobin in patients with gastric cancer.Oncotarget · 2017Observational
- Native Mass Spectrometry: What is in the Name?Journal of the American Society for Mass Spectrometry · 2017Article
- The diverse and expanding role of mass spectrometry in structural and molecular biology.The EMBO journal · 2016Review
- Use of a charge reducing agent to enable intact mass analysis of cysteine-linked antibody-drug-conjugates by native mass spectrometry.EuPA open proteomics · 2016Article
- Optimal Synthetic Glycosylation of a Therapeutic Antibody.Angewandte Chemie (International ed. in English) · 2016Article
- Optimal Synthetic Glycosylation of a Therapeutic Antibody.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2016Article
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6 authors.
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Abstract
Here, we describe a fast, easy-to-use, and sensitive method to profile in-depth structural micro-heterogeneity, including intricate N-glycosylation profiles, of monoclonal antibodies at the native intact protein level by means of mass spectrometry using a recently introduced modified Orbitrap Exactive Plus mass spectrometer. We demonstrate the versatility of our method to probe structural micro-heterogeneity by describing the analysis of three types of molecules: (1) a non-covalently bound IgG4 hinge deleted full-antibody in equilibrium with its half-antibody, (2) IgG4 mutants exhibiting highly complex glycosylation profiles, and (3) antibody-drug conjugates. Using the modified instrument, we obtain baseline separation and accurate mass determination of all different proteoforms that may be induced, for example, by glycosylation, drug loading and partial peptide backbone-truncation. We show that our method can handle highly complex glycosylation profiles, identifying more than 20 different glycoforms per monoclonal antibody preparation and more than 30 proteoforms on a single highly purified antibody. In analyzing antibody-drug conjugates, our method also easily identifies and quantifies more than 15 structurally different proteoforms that may result from the collective differences in drug loading and glycosylation. The method presented here will aid in the comprehensive analytical and functional characterization of protein micro-heterogeneity, which is crucial for successful development and manufacturing of therapeutic antibodies.
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