Oxidation of M252 but not M428 in hu-IgG1 is responsible for decreased binding to and activation of hu-FcγRIIa (His131)
| Autor: | Hermann Beck, Tilman Schlothauer, Cecile Avenal, Florian Cymer, Daniel Gygax, Harald Wegele, Marco Thomann |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.drug_class Antibody Affinity Bioengineering Monoclonal antibody 030226 pharmacology & pharmacy Applied Microbiology and Biotechnology Mass Spectrometry 03 medical and health sciences chemistry.chemical_compound Methionine 0302 clinical medicine Affinity chromatography medicine Humans Histidine Receptor Pharmacology General Immunology and Microbiology biology Chemistry Receptors IgG Antibodies Monoclonal General Medicine Surface Plasmon Resonance 030104 developmental biology Biochemistry Immunoglobulin G Monoclonal biology.protein Fc-Gamma Receptor Antibody Oxidation-Reduction Chromatography Liquid Protein Binding Biotechnology |
| Zdroj: | Biologicals. 50:125-128 |
| ISSN: | 1045-1056 |
| DOI: | 10.1016/j.biologicals.2017.09.006 |
| Popis: | Oxidation of monoclonal therapeutic antibodies (mAbs) can affect binding to Fc-receptors and potentially influence pharmacokinetics or effector functions like e.g. antibody dependent cellular phagocytosis (ADCP). Recently, it has been demonstrated that binding to FcγRIIa (H131) is affected by methionine oxidation of the Fc-portion but it is currently unknown which methionine is responsible for decreased binding. We separated an oxidized IgG1 monoclonal antibody based on the oxidation state of methionine 252 and analyzed fractionated material in receptor binding experiments as well as in functional (cell-based) assays. Although the unfractionated mixture demonstrated weaker interaction/activation of the receptor, differently oxidized isolated subspecies can lead both to stronger as well as weaker binding and activation of the histidine variant of FcγRIIa. |
| Databáze: | OpenAIRE |
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