ArticlePharmaceutical research2018
Effect of Chemical Oxidation on the Higher Order Structure, Stability, Aggregation, and Biological Function of Interferon Alpha-2a: Role of Local Structural Changes Detected by 2D NMR.
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 10 papers.
What it found
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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.
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Who cites it
10 citing papers in PubMed.
- Mobile Affinity Selection Chromatography Analysis of Therapeutic Monoclonal Antibodies.Analytical chemistry · 2023Article
- Expression ofEPJ web of conferences · 2023Article
- Integration of NMR Spectroscopy in an Analytical Workflow to Evaluate the Effects of Oxidative Stress on Abituzumab: Beyond the Fingerprint of mAbs.Analytical chemistry · 2023Article
- Aggregation of protein therapeutics enhances their immunogenicity: causes and mitigation strategies.RSC chemical biology · 2021Review
- NMR Spectroscopy for Protein Higher Order Structure Similarity Assessment in Formulated Drug Products.Molecules (Basel, Switzerland) · 2021Article
- Pharmacokinetics Versus In Vitro Antiproliferative Potency to Design a Novel Hyperglycosylated hIFN-α2 Biobetter.Pharmaceutical research · 2021Article
- Role of NMR in High Ordered Structure Characterization of Monoclonal Antibodies.International journal of molecular sciences · 2020Review
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Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeOxidized interferons have been shown to aggregate and cause immunogenicity. In this study, the structural mechanisms underlying oxidation-induced interferon alpha-2a (IFNA2a) aggregation and loss of function were examined.
methodsIFNA2a was oxidized using 0.037% vol/vol hydrogen peroxide. Oxidized protein was probed using biophysical methods that include denaturant melts, particle counting, proteolysis-coupled mass spectrometry, and 2D NMR.
resultsOxidized IFNA2a did not show major changes in its secondary structure, but showed minor changes in tertiary structure when compared to the unoxidized protein. In addition, a significant loss of conformational stability was observed upon oxidation. Correspondingly, increased protein aggregation was observed resulting in the formation of sub-visible particles. Oxidized protein showed decreased biological function in terms of its anti-viral potency and cytopathic inhibition efficacy. Proteolysis-coupled mass spectrometry identified five methionine residues that were oxidized with no correlation between the extent of oxidation and their accessible surface area. 2D
conclusionsIncreased protein aggregation and decreased function of IFNA2a upon oxidation correlated with the site of modification identified by proteolysis-coupled mass spectrometry and local structural changes in the protein detected by 2D NMR.
Indexed as
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30324266What OpenQuestion holds
Registered trials
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