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Updated: Feb 8, 2026

LERLIC-MS/MS for In-depth Characterization and Quantification of Glutamine and Asparagine Deamidation in Shotgun Proteomics
Published on: April 9, 2017
Structure Based Prediction of Asparagine Deamidation Propensity in Monoclonal Antibodies
Qingrong Yan1, Maggie Huang1, Michael J Lewis1
1a Large Molecule Analytical Development, Pharmaceutical Development and Manufacturing Sciences , Janssen R&D, LLC , Malvern , PA , USA.
Abstract:
Identification of asparagine (Asn) sites that are prone to deamidation is critical for the development of therapeutic monoclonal antibodies (mAbs). Despite a common chemical degradation pathway, the rates of Asn deamidation can vary dramatically among different sites, and prediction of the sensitive deamidation sites is still challenging. In this study, characterization of Asn deamidation for five IgG1 and five IgG4 mAbs under both normal and stressed conditions revealed dramatic differences in the Asn deamidation rates. A comprehensive analysis of the deamidation sites indicated that the deamidation rate differences could be explained by differences in the local structure conformation, structure flexibility and solvent accessibility. A decision tree was developed to predict the deamidation propensity for all Asn sites in IgG mAbs based on the analysis of these three structural parameters. This decision tree will allow potential Asn deamidation hot spots to be identified early in development.
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