One- and two-electron oxidations of β-amyloid25-35 by carbonate radical anion (CO3•-) and peroxymonocarbonate (HCO4-): role of sulfur in radical reactions and peptide aggregation
| Autor: | Simone Dinarelli, Alessandra Giorgi, Luciana Mosca, Elita Montanari, Cesira Foppoli, Antonio Francioso, Mario Fontana, Alessia Baseggio Conrado, Carla Blarzino |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
sulfur centered radical
Bicarbonate Pharmaceutical Science chemistry.chemical_element Carbonate radical anion Medicinal chemistry Analytical Chemistry lcsh:QD241-441 03 medical and health sciences chemistry.chemical_compound Residue (chemistry) methionine sulfoxide 0302 clinical medicine lcsh:Organic chemistry Thioether peroxymonocarbonate reactive sulfur species Drug Discovery sulfur radical cation Physical and Theoretical Chemistry Free Radical Formation 030304 developmental biology 0303 health sciences Methionine sulfoxide β-amyloid Organic Chemistry Sulfoxide Sulfur chemistry Radical ion Chemistry (miscellaneous) Molecular Medicine 030217 neurology & neurosurgery |
| Zdroj: | Molecules Volume 25 Issue 4 Molecules, Vol 25, Iss 4, p 961 (2020) |
| Popis: | The &beta amyloid (A&beta ) peptide plays a key role in the pathogenesis of Alzheimer&rsquo s disease. The methionine (Met) residue at position 35 in A&beta C-terminal domain is critical for neurotoxicity, aggregation, and free radical formation initiated by the peptide. The role of Met in modulating toxicological properties of A&beta most likely involves an oxidative event at the sulfur atom. We therefore investigated the one- or two-electron oxidation of the Met residue of A&beta 25-35 fragment and the effect of such oxidation on the behavior of the peptide. Bicarbonate promotes two-electron oxidations mediated by hydrogen peroxide after generation of peroxymonocarbonate (HCO4&minus PMC). The bicarbonate/carbon dioxide pair stimulates one-electron oxidations mediated by carbonate radical anion (CO3&bull &minus ). PMC efficiently oxidizes thioether sulfur of the Met residue to sulfoxide. Interestingly, such oxidation hampers the tendency of A&beta to aggregate. Conversely, CO3&bull causes the one-electron oxidation of methionine residue to sulfur radical cation (MetS&bull +). The formation of this transient reactive intermediate during A&beta oxidation may play an important role in the process underlying amyloid neurotoxicity and free radical generation. |
| Databáze: | OpenAIRE |
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