ArticleJournal of pharmaceutical sciences2014
Detection and quantitation of succinimide in intact protein via hydrazine trapping and chemical derivatization.
Article in Journal of pharmaceutical sciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Developments in Ion Exchange Chromatography-Mass Spectrometry for the Characterization of Intact Proteins and Proteoforms.Journal of separation science · 2025Review
- Cysimiditides: RiPPs with a Zn-Tetracysteine Motif and Aspartimidylation.Biochemistry · 2025Article
- 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
- Deuterium Labeling of Isoaspartic and Isoglutamic Acids for Mass Spectrometry Analysis.Analytical chemistry · 2024Article
- Enzymatic Fluoromethylation as a Tool for ATP-Independent Ligation.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2024Article
- Enzymatic Fluoromethylation as a Tool for ATP-Independent Ligation.Angewandte Chemie (International ed. in English) · 2024Article
- Evolutionary Spread of Distinct O-methyltransferases Guides the Discovery of Unique Isoaspartate-Containing Peptides, Pamtides.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Biosynthesis and characterization of fuscimiditide, an aspartimidylated graspetide.Nature chemistry · 2022Article
- PIMT-Mediated Labeling of l-Isoaspartic Acid with Tris Facilitates Identification of Isomerization Sites in Long-Lived Proteins.Journal of the American Society for Mass Spectrometry · 2022Article
- Cellulonodin-2 and Lihuanodin: Lasso Peptides with an Aspartimide Post-Translational Modification.Journal of the American Chemical Society · 2021Article
- Chemical Properties Determine Solubility and Stability in βγ-Crystallins of the Eye Lens.Chembiochem : a European journal of chemical biology · 2021Review
- Understanding the pathway and kinetics of aspartic acid isomerization in peptide mapping methods for monoclonal antibodies.Analytical and bioanalytical chemistry · 2021Article
- Discovery of Electrophiles and Profiling of Enzyme Cofactors.Current protocols in chemical biology · 2020Article
- 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
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- Chemoproteomic profiling and discovery of protein electrophiles in human cells.Nature chemistry · 2017Article
- Mass Spectrometry Based Mechanistic Insights into Formation of Tris Conjugates: Implications on Protein Biopharmaceutics.Journal of the American Society for Mass Spectrometry · 2016Article
- Mildly acidic conditions eliminate deamidation artifact during proteolysis: digestion with endoprotease Glu-C at pH 4.5.Amino acids · 2016Article
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Authors and funding
4 authors.
Funding
Abstract
The formation of aspartyl succinimide is a common post-translational modification of protein pharmaceuticals under acidic conditions. We present a method to detect and quantitate succinimide in intact protein via hydrazine trapping and chemical derivatization. Succinimide, which is labile under typical analytical conditions, is first trapped with hydrazine to form stable hydrazide and can be directly analyzed by mass spectrometry. The resulting aspartyl hydrazide can be selectively derivatized by various tags, such as fluorescent rhodamine sulfonyl chloride that absorbs strongly in the visible region (570 nm). Our tagging strategy allows the labeled protein to be analyzed by orthogonal methods, including HPLC-UV-Vis, liquid chromatography mass spectrometry (LC-MS), and SDS-PAGE coupled with fluorescence imaging. A unique advantage of our method is that variants containing succinimide, after derivatization, can be readily resolved via either affinity enrichment or chromatographic separation. This allows further investigation of individual factors in a complex protein mixture that affect succinimide formation. Some additional advantages are imparted by fluorescence labeling including the facile detection of the intact protein without proteolytic digestion to peptides; and high sensitivity, for example, without optimization, 0.41% succinimide was readily detected. As such, our method should be useful for rapid screening, optimization of formulation conditions, and related processes relevant to protein pharmaceuticals.
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