The disulfide bond structures established decades ago for immunoglobulins have been challenged by findings from extensive characterization of recombinant and human monoclonal IgG antibodies. Non-classical disulfide bond structure was first identified in IgG4 and later in IgG2 antibodies. Although, cysteine residues should be in the disulfide bonded states, free sulfhydryls have been detected in all subclasses of IgG antibodies. In addition, disulfide bonds are susceptible to chemical modifications, which can further generate structural variants such as IgG antibodies with trisulfide bond or thioether linkages. Trisulfide bond formation has also been observed for IgG of all subclasses. Degradation of disulfide bond through β-elimination generates free sulfhydryls disulfide and dehydroalanine. Further reaction between free sulfhydryl and dehydroalanine leads to the formation of a non-reducible cross-linked species. Hydrolysis of the dehydroalanine residue contributes substantially to antibody hinge region fragmentation. The effect of these disulfide bond variations on antibody structure, stability and biological function are discussed in this review.
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Characterization of therapeutic antibody fragmentation using automated capillary western blotting as an orthogonal analytical technique
Matching pH values for antibody stabilization and crystallization suggest rationale for accelerated development of biotherapeutic drugs
IgG3 enhances neutralization potency and Fc effector function of an HIV V2-specific broadly neutralizing antibody
Inter-assay variability in automated serum free light chain assays and their use in the clinical laboratory.
Reprogramming the Constant Region of Immunoglobulin G Subclasses for Enhanced Therapeutic Potency against Cancer.
Complete mapping of disulfide linkages for etanercept products by multi-enzyme digestion coupled with LC-MS/MS using multi-fragmentations including CID and ETD
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Investigation of monoclonal antibody dimers in a final formulated drug by separation techniques coupled to native mass spectrometry.
Dynamics of inter-heavy chain interactions in human immunoglobulin G (IgG) subclasses studied by kinetic Fab arm exchange.
Immunoglobulin G; structure and functional implications of different subclass modifications in initiation and resolution of allergy
Enrichment of high affinity subclasses and glycoforms from serum-derived IgG using FcγRs as affinity ligands
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Compactness of Protein Folds Alters Disulfide-Bond Reducibility by Three Orders of Magnitude: A Comprehensive Kinetic Case Study on the Reduction of Differently Sized Tryptophan Cage Model Proteins.
A synopsis of recent developments defining how N-glycosylation impacts immunoglobulin G structure and function
Highly robust and optimized conjugation of antibodies to nanoparticles using quantitatively validated protocols
Detection and quantification of free sulfhydryls in monoclonal antibodies using maleimide labeling and mass spectrometry
Proteoform-Resolved FcɤRIIIa Binding Assay for Fab Glycosylated Monoclonal Antibodies Achieved by Affinity Chromatography Mass Spectrometry of Fc Moieties
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Constructive approach for synthesis of a functional IgG using a reconstituted cell-free protein synthesis system
Optimization and kinetic modeling of interchain disulfide bond reoxidation of monoclonal antibodies in bioprocesses.
SAXS studies of X-ray induced disulfide bond damage: Engineering high-resolution insight from a low-resolution technique
Crystal Structure and Characterization of Human Heavy-Chain Only Antibodies Reveals a Novel, Stable Dimeric Structure Similar to Monoclonal Antibodies
Comprehensive Analysis of Tryptic Peptides Arising from Disulfide Linkages in NISTmAb and Their Use for Developing a Mass Spectral Library.
Biosimilar or Not: Physicochemical and Biological Characterization of MabThera and Its Two Biosimilar Candidates.
Determination of free sulfhydryl contents for proteins including monoclonal antibodies by use of SoloVPE.
Andrographolide Against Lung Cancer-New Pharmacological Insights Based on High-Throughput Metabolomics Analysis Combined with Network Pharmacology.
Antibody disulfide bond reduction and recovery during biopharmaceutical process development-A review.
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