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To reduce cellular oxidative stress caused by overproduction of superoxide, we developed a compound that reacts with O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>.\u2212<\/jats:sup>\n                    to release a persulfide (RSSH), a type of reactive sulfur species related to the gasotransmitter hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S). Termed\n                    <jats:bold>SOPD\u2010NAC<\/jats:bold>\n                    , this persulfide donor reacts specifically with O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>.\u2212<\/jats:sup>\n                    , decomposing to generate\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyl cysteine (NAC) persulfide. To enhance persulfide delivery to cells, we conjugated the SOPD motif to a short, self\u2010assembling peptide (Bz\u2010CFFE\u2010NH\n                    <jats:sub>2<\/jats:sub>\n                    ) to make a superoxide\u2010responsive, persulfide\u2010donating peptide (\n                    <jats:bold>SOPD\u2010Pep<\/jats:bold>\n                    ). Both\n                    <jats:bold>SOPD\u2010NAC<\/jats:bold>\n                    and\n                    <jats:bold>SOPD\u2010Pep<\/jats:bold>\n                    delivered persulfides\/H\n                    <jats:sub>2<\/jats:sub>\n                    S to H9C2 cardiomyocytes and lowered ROS levels as confirmed by quantitative in vitro fluorescence imaging studies. Additional in vitro studies on RAW 264.7 macrophages showed that\n                    <jats:bold>SOPD\u2010Pep<\/jats:bold>\n                    mitigated toxicity induced by phorbol 12\u2010myristate 13\u2010acetate (PMA) more effectively than\n                    <jats:bold>SOPD\u2010NAC<\/jats:bold>\n                    and several control compounds, including common H\n                    <jats:sub>2<\/jats:sub>\n                    S donors.\n                  <\/jats:p>","DOI":"10.1002\/anie.202006656","type":"journal-article","created":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T06:18:21Z","timestamp":1593238701000},"page":"16698-16704","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Alleviating Cellular Oxidative Stress through Treatment with Superoxide\u2010Triggered Persulfide Prodrugs"],"prefix":"10.1002","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6729-7230","authenticated-orcid":false,"given":"Yin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of of Chemistry Virginia Tech Center for Drug Discovery Macromolecules Innovation Institute Virginia Tech  Blacksburg VA 24061 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0147-8730","authenticated-orcid":false,"given":"Kearsley M.","family":"Dillon","sequence":"additional","affiliation":[{"name":"Department of of Chemistry Virginia Tech Center for Drug Discovery Macromolecules Innovation Institute Virginia Tech  Blacksburg VA 24061 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0457-3020","authenticated-orcid":false,"given":"Zhao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of of Chemistry Virginia Tech Center for Drug Discovery Macromolecules Innovation Institute Virginia Tech  Blacksburg VA 24061 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan W.","family":"Winckler","sequence":"additional","affiliation":[{"name":"Department of of Chemistry Virginia Tech Center for Drug Discovery Macromolecules Innovation Institute Virginia Tech  Blacksburg VA 24061 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7984-5396","authenticated-orcid":false,"given":"John B.","family":"Matson","sequence":"additional","affiliation":[{"name":"Department of of Chemistry Virginia Tech Center for Drug Discovery Macromolecules Innovation Institute Virginia Tech  Blacksburg VA 24061 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,23]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.30.18515"},{"key":"e_1_2_6_2_1","first-page":"658","volume":"77","author":"Bandyopadhyay U.","year":"1999","journal-title":"Curr. 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