ArticleAnalytical chemistry2013
Discovery of undefined protein cross-linking chemistry: a comprehensive methodology utilizing 18O-labeling and mass spectrometry.
Article in Analytical chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- First site-specific conjugation method for native goat IgG antibodies via glycan remodeling at the conserved Fc region.Antibody therapeutics · 2024Article
- Site-Specific Conjugation of Native Antibody: Transglutaminase-Mediated Modification of a Conserved Glutamine While Maintaining the Primary Sequence and Core Fc Glycan via Trimming with an Endoglycosidase.Bioconjugate chemistry · 2024Article
- Homocysteinylation and Sulfhydration in Diseases.Current neuropharmacology · 2022Review
- Oxidative Crosslinking of Peptides and Proteins: Mechanisms of Formation, Detection, Characterization and Quantification.Molecules (Basel, Switzerland) · 2021Review
- Detection of Isopeptide Bonds in Monoclonal Antibody Aggregates.Pharmaceutical research · 2021Article
- Light-Induced Histidine Adducts to an IgG1 Molecule Via Oxidized Histidine Residue and the Potential Impact of Polysorbate-20 Concentration.Pharmaceutical research · 2021Article
- Proteomic characterization of the human lens and Cataractogenesis.Expert review of proteomics · 2021Review
- Site-specific conjugation of native antibody.Antibody therapeutics · 2020Article
- Site-specific Bioconjugation and Convergent Click Chemistry Enhances Antibody-Chromophore Conjugate Binding Efficiency.Photochemistry and photobiology · 2020Article
- Chlorpyrifos oxon promotes tubulin aggregation via isopeptide cross-linking between diethoxyphospho-Lys and Glu or Asp: Implications for neurotoxicity.The Journal of biological chemistry · 2018Article
- Microwave-assisted cross-linking of milk proteins induced by microbial transglutaminase.Scientific reports · 2016Article
- Mass Spectrometry Based Mechanistic Insights into Formation of Tris Conjugates: Implications on Protein Biopharmaceutics.Journal of the American Society for Mass Spectrometry · 2016Article
- Comparison of Protein N-Homocysteinylation in Rat Plasma under Elevated Homocysteine Using a Specific Chemical Labeling Method.Molecules (Basel, Switzerland) · 2016Article
- Mildly acidic conditions eliminate deamidation artifact during proteolysis: digestion with endoprotease Glu-C at pH 4.5.Amino acids · 2016Article
- Kojak: efficient analysis of chemically cross-linked protein complexes.Journal of proteome research · 2015Article
- Detection and quantitation of succinimide in intact protein via hydrazine trapping and chemical derivatization.Journal of pharmaceutical sciences · 2014Article
- Discovery of a chemical modification by citric acid in a recombinant monoclonal antibody.Analytical chemistry · 2014Article
- Discovery and characterization of a photo-oxidative histidine-histidine cross-link in IgG1 antibody utilizing ¹⁸O-labeling and mass spectrometry.Analytical chemistry · 2014Article
- Arginine modifications by methylglyoxal: discovery in a recombinant monoclonal antibody and contribution to acidic species.Analytical chemistry · 2013Article
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Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Characterization of protein cross-linking, particularly without prior knowledge of the chemical nature and site of cross-linking, poses a significant challenge, because of their intrinsic structural complexity and the lack of a comprehensive analytical approach. Toward this end, we have developed a generally applicable workflow-XChem-Finder-that involves four stages: (1) detection of cross-linked peptides via (18)O-labeling at C-termini; (2) determination of the putative partial sequences of each cross-linked peptide pair using a fragment ion mass database search against known protein sequences coupled with a de novo sequence tag search; (3) extension to full sequences based on protease specificity, the unique combination of mass, and other constraints; and (4) deduction of cross-linking chemistry and site. The mass difference between the sum of two putative full-length peptides and the cross-linked peptide provides the formulas (elemental composition analysis) for the functional groups involved in each cross-linking. Combined with sequence restraint from MS/MS data, plausible cross-linking chemistry and site were inferred, and ultimately confirmed, by matching with all data. Applying our approach to a stressed IgG2 antibody, 10 cross-linked peptides were discovered and found to be connected via thioethers originating from disulfides at locations that had not been previously recognized. Furthermore, once the cross-link chemistry was revealed, a targeted cross-link search yielded 4 additional cross-linked peptides that all contain the C-terminus of the light chain.
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Registered trials
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