ArticlePharmaceutical research2018
Impact of Tryptophan Oxidation in Complementarity-Determining Regions of Two Monoclonal Antibodies on Structure-Function Characterized by Hydrogen-Deuterium Exchange Mass Spectrometry and Surface Plasmon Resonance.
Article in Pharmaceutical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed.
- Article
- Phage Display Technology: Design, Library Construction, and Panning Strategies for Antibody Development.Biomolecules & therapeutics · 2026Review
- Reconciling specificity and non-specificity in antibody binding: an energy landscape framework for immunology education.Frontiers in immunology · 2025Article
- Understanding the Specific Implications of Amino Acids in the Antibody Development.The protein journal · 2024Review
- Preclinical development of humanized monoclonal antibodies against CD169 as a broad antiviral therapeutic strategy.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Selectivity and Resolving Power of Hydrophobic Interaction Chromatography Targeting the Separation of Monoclonal Antibody Variants.Analytical chemistry · 2024Article
- Introduction of Carbonyl Groups into Antibodies.Molecules (Basel, Switzerland) · 2023Review
- Developability assessment at early-stage discovery to enable development of antibody-derived therapeutics.Antibody therapeutics · 2023Review
- Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems.Chemical reviews · 2022Review
- Functional Changes of Therapeutic Antibodies upon Exposure to Pro-Oxidative Agents.Antibodies (Basel, Switzerland) · 2022Article
- Photo-Oxidation of Therapeutic Protein Formulations: From Radical Formation to Analytical Techniques.Pharmaceutics · 2021Review
- Optimization of therapeutic antibodies.Antibody therapeutics · 2021Review
- Forced Degradation Testing as Complementary Tool for Biosimilarity Assessment.Bioengineering (Basel, Switzerland) · 2019Article
- Applying the science of measurement to biology: Why bother?PLoS biology · 2019Article
- A photochemical and theoretical study of the triplet reactivity of furano- and pyrano-1,4-naphthoquionones towards tyrosine and tryptophan derivatives.RSC advances · 2019Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTryptophan's (Trp) unique hydrophobic and structural properties make it an important antigen binding motif when positioned in complementarity-determining regions (CDRs) of monoclonal antibodies (mAbs). Oxidation of Trp residues within the CDR can deleteriously impact antigen binding, particularly if the CDR conformation is altered. The goal of this study was to evaluate the conformational and functional impact of Trp oxidation for two mAb subtypes, which is essential in determining the structure-function relationship and establishing appropriate analytical control strategies during protein therapeutics development.
methodsSelective Trp oxidation was induced by 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) treatment in the presence of free methionine (Met). The native and chemically oxidized mAbs were characterized by hydrogen-deuterium exchange mass spectrometry (HDX-MS) for conformational changes and surface plasmon resonance (SPR) for antigen-antibody binding.
resultsTreatment of mAbs with AAPH selectively oxidized solvent accessible Trp residues. Oxidation of Trp within or in proximity of CDRs increased conformational flexibility in variable domains and disrupted antigen binding.
conclusionsTrp oxidation in CDRs can adversely impact mAbs' conformation and antigen binding. Trp oxidation should be carefully evaluated as part of critical quality attribute assessments. Oxidation susceptible Trp should be closely monitored during process development for mAbs to establish appropriate analytical control for manufacturing of drug substance and drug product.
Indexed as
Identifiers
What OpenQuestion holds
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.