Sensitization to p-amino aromatic compounds: Study of the covalent binding of 2,5-dimethyl-p-benzoquinonediimine to a model peptide by electrospray ionization tandem mass spectrometry.

Abstract

To understand the hapten-protein complex formation in the context of skin contact allergy to p-amino aromatic derivatives, 2,5-dimethyl-p-benzoquinonediimine was used as a model compound to study the reactivity of p-benzoquinonediimines, first oxidation intermediates of allergenic p-amino aromatic compounds, toward a model peptide containing naturally occurring and potential reactive amino acids. LC-MS analysis, together with electrospray ionization MS/MS, was used for the determination of amino acid selectivity by studying the chemical modifications induced on the peptide due to covalent binding of the p-benzoquinonediimine. Results reported in this paper indicated that 2,5-dimethyl-p-benzoquinonediimine reacted with the epsilon-NH(2) group of lysine to first form a covalent adduct of the Schiff's base kind. Besides, an oxido-reduction process started that induced an oxidative deamination of lysine to form a peptidyl alpha-aminoadipic-delta-semialdehyde, by a mechanism similar to the one known for several enzymatic quinonoid co-factors, followed by an intramolecular cyclization of the peptide. From these results it could be concluded that lysine must be considered as an important amino acid for the hapten-protein complex formation in the case of p-benzoquinonediimines and that, in addition to direct covalent binding, further degradation of the peptide can be produced.

• Authors: Joan Eilstein, Elena Giménez-Arnau, Daniel Duché, Nükhet Cavusoglu, Georges Hussler, Françoise Rousset, Jean-Pierre Lepoittevin
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 16 Issue 10 Pg. 5482-9 (May 15 2008) ISSN: 1464-3391 [Electronic] England
• PMID: 18448343 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2,5-dimethyl-4-benzoquinonediimine
• Haptens
• Imines
• Peptides

Topics

• Binding Sites
• Chromatography, Liquid (methods)
• Dermatitis, Contact
• Haptens (chemistry)
• Imines (chemistry)
• Kinetics
• Models, Molecular
• Molecular Structure
• Peptides (chemistry)
• Reproducibility of Results
• Sensitivity and Specificity
• Spectrometry, Mass, Electrospray Ionization (methods)
• Stereoisomerism
• Tandem Mass Spectrometry (methods)
• Time Factors