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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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Autores principales: Ishkaeva, Rezeda A., Nizamov, Ilyas S., Blokhin, Dmitriy S., Urakova, Elizaveta A., Klochkov, Vladimir V., Nizamov, Ilnar D., Gareev, Bulat I., Salakhieva, Diana V., Abdullin, Timur I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157023/
https://www.ncbi.nlm.nih.gov/pubmed/34067789
http://dx.doi.org/10.3390/molecules26102973
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author Ishkaeva, Rezeda A.
Nizamov, Ilyas S.
Blokhin, Dmitriy S.
Urakova, Elizaveta A.
Klochkov, Vladimir V.
Nizamov, Ilnar D.
Gareev, Bulat I.
Salakhieva, Diana V.
Abdullin, Timur I.
author_facet Ishkaeva, Rezeda A.
Nizamov, Ilyas S.
Blokhin, Dmitriy S.
Urakova, Elizaveta A.
Klochkov, Vladimir V.
Nizamov, Ilnar D.
Gareev, Bulat I.
Salakhieva, Diana V.
Abdullin, Timur I.
author_sort Ishkaeva, Rezeda A.
collection PubMed
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.
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spelling pubmed-81570232021-05-28 Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione Ishkaeva, Rezeda A. Nizamov, Ilyas S. Blokhin, Dmitriy S. Urakova, Elizaveta A. Klochkov, Vladimir V. Nizamov, Ilnar D. Gareev, Bulat I. Salakhieva, Diana V. Abdullin, Timur I. Molecules Article 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. MDPI 2021-05-17 /pmc/articles/PMC8157023/ /pubmed/34067789 http://dx.doi.org/10.3390/molecules26102973 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ishkaeva, Rezeda A.
Nizamov, Ilyas S.
Blokhin, Dmitriy S.
Urakova, Elizaveta A.
Klochkov, Vladimir V.
Nizamov, Ilnar D.
Gareev, Bulat I.
Salakhieva, Diana V.
Abdullin, Timur I.
Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157023/
https://www.ncbi.nlm.nih.gov/pubmed/34067789
http://dx.doi.org/10.3390/molecules26102973
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