Oxidation of therapeutic proteins and peptides: structural and biological consequences.
Oxidation is a common degradation pathway that affects therapeutic proteins and peptides during production, purification, formulation, transportation, storage and handling of solid and liquid preparations. In the present work we review the scientific literature about structural and biological consequences of protein/peptide oxidation. Representative examples are discussed of specific products whose oxidation has been recently studied, including monoclonal antibodies, calcitonin, granulocyte colony-stimulating factor, growth hormone, insulin, interferon alpha and beta, oxytocin and parathyroid hormone. These examples illustrate that oxidation often leads to modifications of higher-order structures, including aggregate induction, and can generate products that are pharmacokinetically different, biologically less active and/or potentially more immunogenic than their native counterpart. It is therefore crucially important during the pharmaceutical development of therapeutic proteins and peptides to comprehensively characterize oxidation products and evaluate the impact of oxidation-induced structural modifications on the biological properties of the drug.
Division of Drug Delivery Technology Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
Riccardo
R
Torosantucci
Christian
C
Schöneich
Wim
W
Jiskoot
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical / Q000379:methods; D006801:Humans; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry* / Q000627:therapeutic use; D011506:Proteins / Q000737:chemistry* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000737:chemistry / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D010455:Peptides; D011506:Proteins; D011994:Recombinant Proteins