ArticleAnalytical chemistry2026
Stereochemical and Structural Characterization of Methionine Oxidation in the IgG1 Fc Region by Integrated NMR and LC-MS Analysis.
Article in Analytical chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Monoclonal antibodies are widely used biotherapeutics, whose efficacy and pharmacokinetics critically depend on their structural integrity. Among chemical degradation pathways, methionine oxidation is a particularly important post-translational modification that compromises antibody stability, Fc receptor binding, and thereby FcRn-mediated recycling and FcγR-mediated effector functions. However, the structural consequences of oxidation remain poorly understood, largely due to the subtle and localized nature of the modification. Here, we present an integrated analytical framework combining methyl-based NMR spectroscopy, selective enzymatic reduction, and peptide mapping to resolve methionine oxidation in the Fc region of human IgG1 antibodies at residue- and stereochemical-level resolution. By selectively labeling methionine methyl groups, we monitored oxidation-induced spectral changes in conserved Fc residues Met252 and Met428. Site-directed mutagenesis revealed a mutual influence between these residues, consistent with their spatial proximity at the C
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