ArticlemAbs
Structural analysis of a therapeutic monoclonal antibody dimer by hydroxyl radical footprinting.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 67 citations in OpenAlex.
- Article
- Structural exposure of different microtubule binding domains determines the propagation and toxicity of pathogenic tau conformers in Alzheimer's disease.PLoS pathogens · 2025Article
- Mapping conformational changes on bispecific antigen-binding biotherapeutic by covalent labeling and mass spectrometry.Journal of pharmaceutical analysis · 2024Article
- A Novel Platform for Evaluating Dose Rate Effects on Oxidative Damage to Peptides: Toward a High-Throughput Method to Characterize the Mechanisms Underlying the FLASH Effect.Radiation research · 2023Article
- Structural Investigation of Therapeutic Antibodies Using Hydroxyl Radical Protein Footprinting Methods.Antibodies (Basel, Switzerland) · 2022Review
- Complementary Structural Information for Antibody-Antigen Complexes from Hydrogen-Deuterium Exchange and Covalent Labeling Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2022Article
- MEMBRANE PROTEIN STRUCTURES AND INTERACTIONS FROM COVALENT LABELING COUPLED WITH MASS SPECTROMETRY.Mass spectrometry reviews · 2022Review
- Expression of functional eGFP-fused antigen-binding fragment of ranibizumab inBioImpacts : BI · 2022Article
- New high-throughput endstation to accelerate the experimental optimization pipeline for synchrotron X-ray footprinting.Journal of synchrotron radiation · 2021Article
- Laser-free Hydroxyl Radical Protein Footprinting to Perform Higher Order Structural Analysis of Proteins.Journal of visualized experiments : JoVE · 2021Article
- Structurally distinct external solvent-exposed domains drive replication of major human prions.PLoS pathogens · 2021Article
- Covalent Labeling/Mass Spectrometry of Monoclonal Antibodies with Diethylpyrocarbonate: Reaction Kinetics for Ensuring Protein Structural Integrity.Journal of the American Society for Mass Spectrometry · 2020Article
- Higher-Order Structure Influences the Kinetics of Diethylpyrocarbonate Covalent Labeling of Proteins.Journal of the American Society for Mass Spectrometry · 2020Article
- Development of Container Free Sample Exposure for Synchrotron X-ray Footprinting.Analytical chemistry · 2020Article
- POT1-TPP1 differentially regulates telomerase via POT1 His266 and as a function of single-stranded telomere DNA length.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Covalent Labeling with Diethylpyrocarbonate: Sensitive to the Residue Microenvironment, Providing Improved Analysis of Protein Higher Order Structure by Mass Spectrometry.Analytical chemistry · 2019Article
- Article
- Recent Advances in X-Ray Hydroxyl Radical Footprinting at the Advanced Light Source Synchrotron.Protein and peptide letters · 2019Article
- Covalent labeling-mass spectrometry with non-specific reagents for studying protein structure and interactions.Methods (San Diego, Calif.) · 2018Review
- Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Hydroxyl radical footprinting is a covalent labeling strategy used to probe the conformational properties of proteins in solution. We describe the first application of this high resolution technique for characterizing the structure of a therapeutic monoclonal antibody (mAb) dimer. As monitored by size-exclusion chromatography (SEC), therapeutic mAbs typically contain small amounts of a dimer species relative to the primary monomeric form in its drug substance or drug product. To determine its structural orientation, a sample enriched in an IgG1 mAb dimer was oxidized by hydroxyl radicals generated by exposure of the aqueous solution to synchrotron X-rays in millisecond timescales. The antibody monomer that served as a control was oxidized in a similar fashion. The oxidized samples were digested with trypsin and analyzed by RP-UHPLC-MS. The footprinting data show that peptides displaying decreased rates of oxidation (i.e., regions of increased protection) in the dimer are localized in the light and heavy chains of the Fab domain. The interface region for the monomers comprising the dimer was thus inferred to be between their Fab arms, allowing us to model two possible theoretical dimer orientations: a head-to-head, single arm-bound Fab-to-Fab dimer, and a head-to-head, double arm-bound Fab (') 2-to-Fab (') 2 dimer. Lower resolution fragment-SEC analysis of the dimer and monomer samples treated with papain or FabRICATOR enzyme provided complimentary evidence to support the Fab/Fab orientation of the IgG1 dimer.
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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.