ArticleNature communications2024
Exposing the molecular heterogeneity of glycosylated biotherapeutics.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed.
- Article
- Development and Integrated Application of the Multi-Attribute Method (MAM) in Quality Control of Biotechnological Drugs.Biotechnology and bioengineering · 2026Review
- Improved Protein Identification in Native Ambient Mass Spectrometry by the Integration of Proton Transfer Charge Reduction and Higher-Energy Collision Dissociation (PTCR-HCD MS3).Journal of the American Society for Mass Spectrometry · 2026Article
- Integrated Phytochemical and Pharmacological Insights intoPlants (Basel, Switzerland) · 2026Review
- Resolving charge and glycosylation variants of cetuximab combining offline ion-exchange and hydrophilic interaction chromatography-HRMS.Analytical and bioanalytical chemistry · 2026Article
- Extending Serum IgG1 Antibody Repertoire Coverage Using DIA-PTCR.Journal of the American Society for Mass Spectrometry · 2026Article
- Proton Transfer Charge Reduction Enables Isobaric Labeling-Based Proteoform Quantification of Overlapping Signals in Top-Down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2026Article
- Automating Middle-Down Mass Spectrometry Analysis for Extensive Antibody Characterization.Analytical chemistry · 2026Article
- Generating 3D models of complex carbohydrates with GLYCAM-Web.Nature methods · 2026Article
- Native Mass Spectrometry-Based Proteomics Reveals the Mechanism of Hemophore Release by PathogenicbioRxiv : the preprint server for biology · 2026Article
- Mass Spectrometry Analysis of Biotherapeutic Monoclonal Antibody Glycosylation.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Posttranslational modifications of heterologous proteins expressed in Nicotiana benthamiana.Plant biotechnology journal · 2026Review
- GLYCO-BUILD: an enzymatic pipeline for the synthesis of peptides carrying eukaryotic N-glycans.Nature communications · 2025Article
- Uncovering hidden protein modifications with native top-down mass spectrometry.Nature methods · 2025Article
- Glycosylation in cancer: mechanisms, diagnostic markers, and therapeutic applications.Molecular and cellular biochemistry · 2025Review
- The biology of interleukin-6 family cytokines is regulated by glycosylation.The Biochemical journal · 2025Review
- AsymmetricJournal of the American Chemical Society · 2024Article
- Cracking the diversity of sweet drugs.Nature chemical biology · 2024Article
- Protein Complex Heterogeneity and Topology Revealed by Electron Capture Charge Reduction and Surface Induced Dissociation.ACS central science · 2024Article
- Protein complex heterogeneity and topology revealed by electron capture charge reduction and surface induced dissociation.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
20 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The heterogeneity inherent in today's biotherapeutics, especially as a result of heavy glycosylation, can affect a molecule's safety and efficacy. Characterizing this heterogeneity is crucial for drug development and quality assessment, but existing methods are limited in their ability to analyze intact glycoproteins or other heterogeneous biotherapeutics. Here, we present an approach to the molecular assessment of biotherapeutics that uses proton-transfer charge-reduction with gas-phase fractionation to analyze intact heterogeneous and/or glycosylated proteins by mass spectrometry. The method provides a detailed landscape of the intact molecular weights present in biotherapeutic protein preparations in a single experiment. For glycoproteins in particular, the method may offer insights into glycan composition when coupled with a suitable bioinformatic strategy. We tested the approach on various biotherapeutic molecules, including Fc-fusion, VHH-fusion, and peptide-bound MHC class II complexes to demonstrate efficacy in measuring the proteoform-level diversity of biotherapeutics. Notably, we inferred the glycoform distribution for hundreds of molecular weights for the eight-times glycosylated fusion drug IL22-Fc, enabling correlations between glycoform sub-populations and the drug's pharmacological properties. Our method is broadly applicable and provides a powerful tool to assess the molecular heterogeneity of emerging biotherapeutics.
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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.