Evidence of covalent interaction of fumaric acid esters with sulfhydryl groups in peptides
| Autor: | Zbyněk Zdráhal, Jitka Ulrichová, Petr Fryčák, Karel Lemr, Wolfgang Wiegrebe |
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| Rok vydání: | 2005 |
| Předmět: |
Spectrometry
Mass Electrospray Ionization Fumaric acid Double bond Dimethyl Fumarate Covalent Interaction Dissociation (chemistry) 030207 dermatology & venereal diseases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Fumarates Nucleophile Organic chemistry Sulfhydryl Compounds Spectroscopy 030304 developmental biology chemistry.chemical_classification 0303 health sciences Atmospheric Pressure chemistry Covalent bond Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Thiol Dermatologic Agents Peptides Cysteine |
| Zdroj: | Journal of Mass Spectrometry. 40:1309-1318 |
| ISSN: | 1096-9888 1076-5174 |
| Popis: | Fumaric acid esters, namely dimethylfumarate, have been used for the treatment of psoriasis for many years. Still, their mode of action is not fully clear. Because addition of nucleophiles to the double bonds of fumarates can occur (Michael analogous addition), a study of the interaction of fumarates with cysteine and cysteine-containing peptides possessing nucleophilic sulfhydryl group was carried out. Experiments were performed in aqueous medium at pH 7.4 and at 37 degrees C to simulate physiological conditions. It was proven by mass spectrometric measurements using an ion-trap and time-of-flight instrument that a covalent bond can form between fumarates and the sulfhydryl group of cysteine or cysteinyl residues in peptides. Structures of the interaction products were elucidated by multistage mass spectrometry applying collision-induced dissociation. Higher reactivity of dimethylfumarate in comparison to monomethylfumarate and fumaric acid was observed. |
| Databáze: | OpenAIRE |
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