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.
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.
Eilstein
Joan
J
Institut de Chimie de Strasbourg (CNRS-ULP), Laboratoire de Dermatochimie, Clinique Dermatologique CHU, 1 Place de l'Hôpital, 67091 Strasbourg, France.
Giménez-Arnau
Elena
E
Duché
Daniel
D
Cavusoglu
Nükhet
N
Hussler
Georges
G
Rousset
Françoise
F
Lepoittevin
Jean-Pierre
JP
D001665:Binding Sites; D002853:Chromatography, Liquid / Q000379:methods; D003877:Dermatitis, Contact; D006241:Haptens / Q000737:chemistry; D007097:Imines / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
C514714:2,5-dimethyl-4-benzoquinonediimine; D006241:Haptens; D007097:Imines; D010455:Peptides