Oxidation Mechanisms and Control Strategies in Peptide and Protein Formulations

Abstract Oxidation represents an important chemical degradation process in formulations of therapeutic peptides and proteins. Potential consequences of peptide and protein oxidation are loss of efficacy, aggregation and/or immunogenicity. Depending on the oxidant(s) present or generated in pharmaceutical formulations, oxidation can target any amino acid, though preferred oxidation targets are the aromatic and sulfur-containing amino acids. The rational development of stable peptide and protein formulations would be greatly assisted by a detailed mechanistic understanding of protein oxidation processes in these formulations. This review will provide an overview about oxidation mechanisms relevant for pharmaceutical peptide and protein formulations. It will cover oxidation mechanisms of peptide and protein amino acids as well as processes which may lead to the formation of oxidants in pharmaceutical formulations, together with a mechanistic analysis of potential mitigation strategies.