Mechanistic insight into the oxidative degradation of monoclonal antibodies: relevance to developability and the design of stable pharmaceutical formulations
Open Access
- 14 May 2026
- journal article
- review article
- Published by Portland Press Ltd. in Biochemical Society Transactions
- Vol. 54 (5) , 523-533
Abstract
Oxidation represents a key pathway for the chemical degradation of therapeutic monoclonal antibodies (mAbs), and chemical liabilities such as amino acid residue oxidation are an integral part of developability studies. Mechanistically, oxidation reactions in formulations of therapeutic mAbs are frequently not well understood, as critical information such as the nature of the oxidant(s) is frequently lacking. This brief review summarizes recent screening and developability studies of therapeutic proteins specifically focusing on oxidative liabilities and discusses these data in view of mechanistic and complementary analytical information on the oxidation of amino acid residues in specific protein sequences.Keywords
Funding Information
- KU | Department of Pharmaceutical Chemistry, University of Kansas (N/A)
This publication has 76 references indexed in Scilit:
- Comparative Evaluation of Disodium Edetate and Diethylenetriaminepentaacetic Acid as Iron Chelators to Prevent Metal -Catalyzed Destabilization of a Therapeutic Monoclonal AntibodyJournal of Pharmaceutical Sciences, 2010
- Elevated cleavage of human immunoglobulin gamma molecules containing a lambda light chain mediated by iron and histidineAnalytical Biochemistry, 2009
- Identifying the site of spin trapping in proteins by a combination of liquid chromatography, ELISA, and off-line tandem mass spectrometryFree Radical Biology and Medicine, 2008
- A comprehensive picture of non‐site specific oxidation of methionine residues by peroxides in protein pharmaceuticalsJournal of Pharmaceutical Sciences, 2004
- Free radical-mediated oxidation of free amino acids and amino acid residues in proteinsAmino Acids, 2003
- Singlet oxygen-mediated damage to proteins and its consequencesBiochemical and Biophysical Research Communications, 2003
- Ability of Lipid Hydroperoxides To Partition into Surfactant Micelles and Alter Lipid Oxidation Rates in EmulsionsJournal of Agricultural and Food Chemistry, 2002
- Absolute Rate Constants for the Reaction of Hypochlorous Acid with Protein Side Chains and Peptide BondsChemical Research in Toxicology, 2001
- Reactions of Fe(II)‐ATP and Fe(II)‐citrate complexes with t‐butyl hydroperoxide and cumyl hydroperoxideFEBS Letters, 1990
- Metal ion-catalyzed oxidation of proteins: Biochemical mechanism and biological consequencesFree Radical Biology and Medicine, 1990