ArticlePharmaceutical research2019
Utility of High Resolution NMR Methods to Probe the Impact of Chemical Modifications on Higher Order Structure of Monoclonal Antibodies in Relation to Antigen Binding.
Article in Pharmaceutical research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Fab-Level LC-MS Assessment of Chain Pairing in Asymmetric Bispecific Antibodies Enabled by IdeS Digestion and Selective Hinge Reduction.Pharmaceutical research · 2026Article
- Recent Advances in Atomic-Resolution NMR Investigations of Monoclonal Antibodies.Biomolecules · 2026Review
- Expression ofEPJ web of conferences · 2023Article
- Utility of High Resolution 2D NMR Fingerprinting in Assessing Viscosity of Therapeutic Monoclonal Antibodies.Pharmaceutical research · 2022Article
- Role of NMR in High Ordered Structure Characterization of Monoclonal Antibodies.International journal of molecular sciences · 2020Review
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Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAn understanding of higher order structure (HOS) of monoclonal antibodies (mAbs) could be critical to predicting its function. Amongst the various factors that can potentially affect HOS of mAbs, chemical modifications that are routinely encountered during production and long-term storage are of significant interest.
methodsTo this end, two Pfizer mAbs were subjected to forced deamidation stress for a period of eight weeks. Samples were aliquoted at various time points and high resolution accurate mass liquid chromatography-mass spectrometry (LC-MS/MS) was performed using low-artifact trypsin digestion (LATD) peptide mapping to identify and quantify chemical modifications. 2D backbone amide and sidechain methyl NMR spectra were acquired to gauge the effect of HOS changes upon chemical modification. Differential scanning calorimetry was also performed to assess the effect of thermal stability of mAbs upon modification. Finally, functional studies via target-binding based ELISA were performed to connect HOS changes to any loss of potency.
resultsThe extent of deamidation in the mAb domains were quantified by LC-MS/MS. The HOS changes as obtained from 2D NMR were mostly localized around the affected sites leaving the overall structure relatively unchanged. The antigen-antibody binding of the mAbs, in spite of deamidation in the Fab region, remains unchanged.
conclusionThis case study provides an integrated approach of relating chemical modifications in mAb domains with possible changes in HOS. This can be potentially used to assess a possible loss of potency within the structure-function paradigm of proteins in an orthogonal manner.
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