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Copper(II)\u2010di\u20102\u2010pyridylketone\u20104,4\u2010dimethyl\u2010thiosemicarbazone (Cu<jats:sup>II<\/jats:sup>\u2010Dp44mT) showed anticancer activity in the submicromolar concentration range in cell culture. The interaction of Cu<jats:sup>II<\/jats:sup>\u2010Dp44mT with thiols leading to their depletion or inhibition was proposed to be involved in this activity. Indeed, Cu<jats:sup>II<\/jats:sup>\u2010Dp44mT can catalyze the oxidation of thiols although with slow kinetics. The present work aims to obtain insights into the catalytic activity and selectivity of Cu<jats:sup>II<\/jats:sup>\u2010Dp44mT toward the oxidation of different biologically relevant thiols. Reduced glutathione (GSH), L\u2010cysteine (Cys), <jats:italic>N<\/jats:italic>\u2010acetylcysteine (NAC), D\u2010penicillamine (D\u2010Pen), and the two model proteins glutaredoxin (Grx) and thioredoxin (Trx) were investigated. Cu<jats:sup>II<\/jats:sup>\u2010Dp44mT catalyzed the oxidation of these thiols with different kinetics, with rates in the following order D\u2010Pen&gt;Cys\u226bNAC&gt;GSH and Trx&gt;Grx. Cu<jats:sup>II<\/jats:sup>\u2010Dp44mT was more efficient than Cu<jats:sup>II<\/jats:sup> chloride for the oxidation of NAC and GSH, but not D\u2010Pen and Cys. In mixtures of biologically relevant concentrations of GSH and either Cys, Trx, or Grx, the oxidation kinetics and spectral properties were similar to that of GSH alone, indicating that the interaction of these thiols with Cu<jats:sup>II<\/jats:sup>\u2010Dp44mT is dominated by GSH. Hence GSH could protect other thiols against potential deleterious oxidation by Cu<jats:sup>II<\/jats:sup>\u2010Dp44mT.<\/jats:p>","DOI":"10.1002\/chem.202304212","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T15:15:27Z","timestamp":1708960527000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Glutathione Protects other Cellular Thiols against Oxidation by Cu<sup>II<\/sup>\u2010Dp44mT"],"prefix":"10.1002","volume":"30","author":[{"given":"Iman","family":"Doumi","sequence":"first","affiliation":[{"name":"Institut de Chimie (UMR 7177) University of Strasbourg \u2013 CNRS  4 rue Blaise Pascal 67000 Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Lang","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry Comparative Biochemistry RPTU Kaiserslautern  Erwin-Schr\u00f6dinger Stra\u00dfe 54 D-67663 Kaiserslautern Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7527-2068","authenticated-orcid":false,"given":"Bertrand","family":"Vileno","sequence":"additional","affiliation":[{"name":"Institut de Chimie (UMR 7177) University of Strasbourg \u2013 CNRS  4 rue Blaise Pascal 67000 Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2141-917X","authenticated-orcid":false,"given":"Marcel","family":"Deponte","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry Comparative Biochemistry RPTU Kaiserslautern  Erwin-Schr\u00f6dinger Stra\u00dfe 54 D-67663 Kaiserslautern Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8013-0806","authenticated-orcid":false,"given":"Peter","family":"Faller","sequence":"additional","affiliation":[{"name":"Institut de Chimie (UMR 7177) University of Strasbourg \u2013 CNRS  4 rue Blaise Pascal 67000 Strasbourg France"},{"name":"Institut Universitaire de France (IUF)  1 rue Descartes 75231 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2021.111620"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CS00945H"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105889"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867324666170705120809"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.07.004"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7487"},{"key":"e_1_2_9_7_1","first-page":"852","volume":"9","author":"Babak M. 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