ArticlemAbs
Resolving the micro-heterogeneity and structural integrity of monoclonal antibodies by hybrid mass spectrometric approaches.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Glycosylation in SARS-CoV-2 variants: A path to infection and recovery.Biochemical pharmacology · 2022Review
- Fast and Ultrasensitive Glycoform Analysis by Supercritical Fluid Chromatography-Tandem Mass Spectrometry.Analytical chemistry · 2022Article
- Structural and Functional Analysis of CEX Fractions Collected from a Novel AvastinPharmaceutics · 2022Article
- High-Resolution Native Mass Spectrometry.Chemical reviews · 2022Review
- Discrepancies between High-Resolution Native and Glycopeptide-Centric Mass Spectrometric Approaches: A Case Study into the Glycosylation of Erythropoietin Variants.Journal of the American Society for Mass Spectrometry · 2021Article
- Exploring the Chemical Space of Protein Glycosylation in Noncovalent Protein Complexes: An Expedition along Different Structural Levels of Human Chorionic Gonadotropin by Employing Mass Spectrometry.Analytical chemistry · 2021Article
- Towards structure-focused glycoproteomics.Biochemical Society transactions · 2021Review
- A Pragmatic Guide to Enrichment Strategies for Mass Spectrometry-Based Glycoproteomics.Molecular & cellular proteomics : MCP · 2021Review
- 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
- A Simple Strategy to Eliminate Hexosylation Bias in the Relative Quantification of N-Glycosylation in Biopharmaceuticals.Angewandte Chemie (International ed. in English) · 2020Article
- Mapping a Conformational Epitope of Hemagglutinin A Using Native Mass Spectrometry and Ultraviolet Photodissociation.Analytical chemistry · 2020Article
- Monitoring of immunoglobulin N- and O-glycosylation in health and disease.Glycobiology · 2020Review
- Structural Analysis of the Glycoprotein Complex Avidin by Tandem-Trapped Ion Mobility Spectrometry-Mass Spectrometry (Tandem-TIMS/MS).Analytical chemistry · 2020Article
- Novel Interface for High-Throughput Analysis of Biotherapeutics by Electrospray Mass Spectrometry.Analytical chemistry · 2020Article
- Neutrophil myeloperoxidase harbors distinct site-specific peculiarities in its glycosylation.The Journal of biological chemistry · 2019Article
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- Quantitative collision-induced unfolding differentiates model antibody-drug conjugates.Protein science : a publication of the Protein Society · 2019Article
- Structural Analysis of Monoclonal Antibodies by Ultrahigh Resolution MALDI In-Source Decay FT-ICR Mass Spectrometry.Analytical chemistry · 2019Article
- Quantitation of Glycopeptides by ESI/MS - size of the peptide part strongly affects the relative proportions and allows discovery of new glycan compositions of Ceruloplasmin.Glycoconjugate journal · 2019Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For therapeutic monoclonal antibodies (mAbs), detailed analysis of the structural integrity and heterogeneity, which results from multiple types of post-translational modifications (PTMs), is relevant to various processes, including product characterization, storage stability and quality control. Despite the recent rapid development of new bioanalytical techniques, it is still challenging to completely characterize the proteoform profile of a mAb. As a nearly indispensable tool in mAb analysis, mass spectrometry (MS) provides unique structural information at multiple levels. Here, we tested a hybrid strategy for the comprehensive characterization of micro-heterogeneity by integrating 2 state-of-the-art MS-based approaches, high-resolution native MS and targeted glycan profiling, to perform complementary analysis at the intact protein level and released glycan level, respectively. We compared the performance of these methods using samples of engineered half-body IgG4s and a panel of mAbs approved for human use. The glycosylation characterization data derived from these approaches were found to be mutually consistent in composition profiling, and complementary in identification and relative-quantitation of low-abundant uncommon glycoforms. In addition, multiple other sources of micro-heterogeneity, such as glycation, lack of glycosylation, and loss of light chains, could be detected by this approach, and the contribution of multiple types of modifications to the overall micro-heterogeneity could be assessed using our superposition algorithm. Our data demonstrate that the hybrid strategy allows reliable and thorough characterization of mAbs, revealing product characteristics that would easily be missed if only a single approach were used.
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