Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione
Phosphorus species are potent modulators of physicochemical and bioactive properties of peptide compounds. O,O-diorganyl dithiophoshoric acids (DTP) form bioactive salts with nitrogen-containing biomolecules; however, their potential as a peptide modifier is poorly known. We synthesized amphiphilic...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/10/2973 |
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| author | Rezeda A. Ishkaeva Ilyas S. Nizamov Dmitriy S. Blokhin Elizaveta A. Urakova Vladimir V. Klochkov Ilnar D. Nizamov Bulat I. Gareev Diana V. Salakhieva Timur I. Abdullin |
| author_facet | Rezeda A. Ishkaeva Ilyas S. Nizamov Dmitriy S. Blokhin Elizaveta A. Urakova Vladimir V. Klochkov Ilnar D. Nizamov Bulat I. Gareev Diana V. Salakhieva Timur I. Abdullin |
| author_sort | Rezeda A. Ishkaeva |
| collection | DOAJ |
| description | Phosphorus species are potent modulators of physicochemical and bioactive properties of peptide compounds. O,O-diorganyl dithiophoshoric acids (DTP) form bioactive salts with nitrogen-containing biomolecules; however, their potential as a peptide modifier is poorly known. We synthesized amphiphilic ammonium salts of O,O-dimenthyl DTP with glutathione, a vital tripeptide with antioxidant, protective and regulatory functions. DTP moiety imparted radical scavenging activity to oxidized glutathione (GSSG), modulated the activity of reduced glutathione (GSH) and profoundly improved adsorption and electrooxidation of both glutathione salts on graphene oxide modified electrode. According to NMR spectroscopy and GC–MS, the dithiophosphates persisted against immediate dissociation in an aqueous solution accompanied by hydrolysis of DTP moiety into phosphoric acid, menthol and hydrogen sulfide as well as in situ thiol-disulfide conversions in peptide moieties due to the oxidation of GSH and reduction of GSSG. The thiol content available in dissolved GSH dithiophosphate was more stable during air oxidation compared with free GSH. GSH and the dithiophosphates, unlike DTP, caused a thiol-dependent reduction of MTS tetrazolium salt. The results for the first time suggest O,O-dimenthyl DTP as a redox modifier for glutathione, which releases hydrogen sulfide and induces biorelevant redox conversions of thiol/disulfide groups. |
| first_indexed | 2024-03-10T11:20:17Z |
| format | Article |
| id | doaj.art-b55695d2231549c688a9d3a3e22acb04 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T11:20:17Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b55695d2231549c688a9d3a3e22acb042023-11-21T20:06:01ZengMDPI AGMolecules1420-30492021-05-012610297310.3390/molecules26102973Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized GlutathioneRezeda A. Ishkaeva0Ilyas S. Nizamov1Dmitriy S. Blokhin2Elizaveta A. Urakova3Vladimir V. Klochkov4Ilnar D. Nizamov5Bulat I. Gareev6Diana V. Salakhieva7Timur I. Abdullin8Department of Biochemistry, Biotechnology, and Pharmacology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaDepartment of High Molecular and Organoelement Compounds, Alexander Butlerov Institute of Chemistry, Kazan Federal University, 420008 Kazan, RussiaDepartment of Biochemistry, Biotechnology, and Pharmacology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaDepartment of Medical Physics, Institute of Physics, Kazan Federal University, 420008 Kazan, RussiaDepartment of Medical Physics, Institute of Physics, Kazan Federal University, 420008 Kazan, RussiaDepartment of High Molecular and Organoelement Compounds, Alexander Butlerov Institute of Chemistry, Kazan Federal University, 420008 Kazan, RussiaLaboratory of Isotope and Element Analysis, Institute of Geology and Petroleum Technologies, Kazan Federal University, 420008 Kazan, RussiaDepartment of Biochemistry, Biotechnology, and Pharmacology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaDepartment of Biochemistry, Biotechnology, and Pharmacology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaPhosphorus species are potent modulators of physicochemical and bioactive properties of peptide compounds. O,O-diorganyl dithiophoshoric acids (DTP) form bioactive salts with nitrogen-containing biomolecules; however, their potential as a peptide modifier is poorly known. We synthesized amphiphilic ammonium salts of O,O-dimenthyl DTP with glutathione, a vital tripeptide with antioxidant, protective and regulatory functions. DTP moiety imparted radical scavenging activity to oxidized glutathione (GSSG), modulated the activity of reduced glutathione (GSH) and profoundly improved adsorption and electrooxidation of both glutathione salts on graphene oxide modified electrode. According to NMR spectroscopy and GC–MS, the dithiophosphates persisted against immediate dissociation in an aqueous solution accompanied by hydrolysis of DTP moiety into phosphoric acid, menthol and hydrogen sulfide as well as in situ thiol-disulfide conversions in peptide moieties due to the oxidation of GSH and reduction of GSSG. The thiol content available in dissolved GSH dithiophosphate was more stable during air oxidation compared with free GSH. GSH and the dithiophosphates, unlike DTP, caused a thiol-dependent reduction of MTS tetrazolium salt. The results for the first time suggest O,O-dimenthyl DTP as a redox modifier for glutathione, which releases hydrogen sulfide and induces biorelevant redox conversions of thiol/disulfide groups.https://www.mdpi.com/1420-3049/26/10/2973glutathionedithiophosphatesredox propertieshydrolytic propertieshydrogen sulfidethiol |
| spellingShingle | Rezeda A. Ishkaeva Ilyas S. Nizamov Dmitriy S. Blokhin Elizaveta A. Urakova Vladimir V. Klochkov Ilnar D. Nizamov Bulat I. Gareev Diana V. Salakhieva Timur I. Abdullin Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione Molecules glutathione dithiophosphates redox properties hydrolytic properties hydrogen sulfide thiol |
| title | Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione |
| title_full | Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione |
| title_fullStr | Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione |
| title_full_unstemmed | Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione |
| title_short | Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione |
| title_sort | dithiophosphate induced redox conversions of reduced and oxidized glutathione |
| topic | glutathione dithiophosphates redox properties hydrolytic properties hydrogen sulfide thiol |
| url | https://www.mdpi.com/1420-3049/26/10/2973 |
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