ArticleMolecular pharmaceutics2013
Identification of oxidation sites and covalent cross-links in metal catalyzed oxidized interferon Beta-1a: potential implications for protein aggregation and immunogenicity.
Article in Molecular pharmaceutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 44 citations in OpenAlex.
- Development of a semi-automated MHC-associated peptide proteomics (MAPPs) method using streptavidin bead-based immunoaffinity capture and nano LC-MS/MS to support immunogenicity risk assessment in drug development.Frontiers in immunology · 2023Article
- Oxidative Crosslinking of Peptides and Proteins: Mechanisms of Formation, Detection, Characterization and Quantification.Molecules (Basel, Switzerland) · 2021Review
- Facile imprinted polymer for label-free highly selective potentiometric sensing of proteins: case of recombinant human erythropoietin.Analytical and bioanalytical chemistry · 2021Article
- Cross-talk between redox signalling and protein aggregation.Biochemical Society transactions · 2020Review
- 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.Pharmaceutical research · 2018Article
- Factors affecting the physical stability (aggregation) of peptide therapeutics.Interface focus · 2017Review
- Chemical and Biophysical Characteristics of Monoclonal Antibody Solutions Containing Aggregates Formed during Metal Catalyzed Oxidation.Pharmaceutical research · 2017Article
- Nanoparticulate Impurities Isolated from Pharmaceutical-Grade Sucrose Are a Potential Threat to Protein Stability.Pharmaceutical research · 2017Article
- Antitumor activity of interferon-β1a in hormone refractory prostate cancer with neuroendocrine differentiation.Journal of endocrinological investigation · 2017Article
- Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges.Journal of pharmaceutical sciences · 2016Review
- Protein oxidation and peroxidation.The Biochemical journal · 2016Review
- Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational Modifications.Journal of immunology research · 2016Review
- Metal-mediated protein oxidation: applications of a modified ELISA-based carbonyl detection assay for complex proteins.Pharmaceutical research · 2015Article
- Oxidation of an exposed methionine instigates the aggregation of glyceraldehyde-3-phosphate dehydrogenase.The Journal of biological chemistry · 2014Article
- Oxidation of therapeutic proteins and peptides: structural and biological consequences.Pharmaceutical research · 2014Review
- Metal and complementary molecular bioimaging in Alzheimer's disease.Frontiers in aging neuroscience · 2014Review
- Immunogenicity of subcutaneously administered therapeutic proteins--a mechanistic perspective.The AAPS journal · 2013Review
- Next Generation Biopharmaceuticals: Product Development.Advances in biochemical engineering/biotechnologyArticle
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Oxidation via Cu(2+)/ascorbate of recombinant human interferon beta-1a (IFNβ1a) leads to highly immunogenic aggregates, however it is unknown which amino acids are modified and how covalent aggregates are formed. In the present work we mapped oxidized and cross-linked amino acid residues in aggregated IFNβ1a, formed via Cu(2+)/ascorbate catalyzed oxidation. Size exclusion chromatography (SEC) was used to confirm extensive aggregation of oxidized IFNβ1a. Circular dichroism and intrinsic fluorescence spectroscopy indicated substantial loss of secondary and tertiary structure, respectively. Derivatization with 4-(aminomethyl)benzenesulfonic acid was used to demonstrate, by fluorescence in combination with SEC, the presence of tyrosine (Tyr) oxidation products. High performance liquid chromatography coupled to electrospray ionization mass spectrometry of reduced, alkylated, and digested protein was employed to localize chemical degradation products. Oxidation products of methionine, histidine, phenylalanine (Phe), tryptophan, and Tyr residues were identified throughout the primary sequence. Covalent cross-links via 1,4- or 1,6-type addition between primary amines and DOCH (2-amino-3-(3,4-dioxocyclohexa-1,5-dien-1-yl)propanoic acid, an oxidation product of Phe and Tyr) were detected. There was no evidence of disulfide bridge, Schiff base, or dityrosine formation. The chemical cross-links identified in this work are most likely responsible for the formation of covalent aggregates of IFNβ1a induced by oxidation, which have previously been shown to be highly immunogenic.
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Registered trials
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