{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:55:36Z","timestamp":1792065336357,"version":"4.4.0"},"reference-count":74,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Italian Ministry of Education, University, and Research (MIUR)-Research Projects of National Interest (PRIN)","doi-asserted-by":"publisher","award":["2015T778JW"],"award-info":[{"award-number":["2015T778JW"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Italian Ministry of Education, University, and Research (MIUR)-Research Projects of National Interest (PRIN)","doi-asserted-by":"publisher","award":["2018\u20132022"],"award-info":[{"award-number":["2018\u20132022"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Departments of Excellence","award":["2015T778JW"],"award-info":[{"award-number":["2015T778JW"]}]},{"name":"Departments of Excellence","award":["2018\u20132022"],"award-info":[{"award-number":["2018\u20132022"]}]},{"name":"COST (European Cooperation in Science and Technology","award":["2015T778JW"],"award-info":[{"award-number":["2015T778JW"]}]},{"name":"COST (European Cooperation in Science and Technology","award":["2018\u20132022"],"award-info":[{"award-number":["2018\u20132022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tau is a widespread neuroprotein that regulates the cytoskeleton assembly. In some neurological disorders, known as tauopathies, tau is dissociated from the microtubule and forms insoluble neurofibrillary tangles. Tau comprises four pseudorepeats (R1\u2013R4), containing one (R1, R2, R4) or two (R3) histidines, that potentially act as metal binding sites. Moreover, Cys291 and Cys322 in R2 and R3, respectively, might have an important role in protein aggregation, through possible disulfide bond formation, and\/or affecting the binding and reactivity of redox-active metal ions, as copper. We, therefore, compare the interaction of copper with octadeca-R3-peptide (R3C) and with the mutant containing an alanine residue (R3A) to assess the role of thiol group. Spectrophotometric titrations allow to calculate the formation constant of the copper(I) complexes, showing a remarkable stronger interaction in the case of R3C (log Kf = 13.4 and 10.5 for copper(I)-R3C and copper(I)-R3A, respectively). We also evaluate the oxidative reactivity associated to these copper complexes in the presence of dopamine and ascorbate. Both R3A and R3C peptides increase the capability of copper to oxidize catechols, but copper-R3C displays a peculiar mechanism due to the presence of cysteine. HPLC-MS analysis shows that cysteine can form disulfide bonds and dopamine-Cys covalent adducts, with potential implication in tau aggregation process.<\/jats:p>","DOI":"10.3390\/ijms231810726","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T23:16:36Z","timestamp":1663197396000},"page":"10726","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Role of the Cysteine in R3 Tau Peptide in Copper Binding and Reactivity"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3256-8699","authenticated-orcid":false,"given":"Chiara","family":"Bacchella","sequence":"first","affiliation":[{"name":"Dipartimento di Chimica, Universit\u00e0 di Pavia, Via Taramelli 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Gentili","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, della Vita e della Sostenibilit\u00e0 Ambientale, Universit\u00e0 di Parma, Parco Area delle Scienze 11\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Ida","family":"Mozzi","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica, Universit\u00e0 di Pavia, Via Taramelli 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8791-6446","authenticated-orcid":false,"given":"Enrico","family":"Monzani","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica, Universit\u00e0 di Pavia, Via Taramelli 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7671-0506","authenticated-orcid":false,"given":"Luigi","family":"Casella","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica, Universit\u00e0 di Pavia, Via Taramelli 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9621-0410","authenticated-orcid":false,"given":"Matteo","family":"Tegoni","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, della Vita e della Sostenibilit\u00e0 Ambientale, Universit\u00e0 di Parma, Parco Area delle Scienze 11\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1231-4045","authenticated-orcid":false,"given":"Simone","family":"Dell\u2019Acqua","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica, Universit\u00e0 di Pavia, Via Taramelli 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1159\/000464422","article-title":"Molecular Pathogenesis of Alzheimer\u2019s Disease: An Update","volume":"24","year":"2017","journal-title":"Ann. 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