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Here, using principles of enzyme\u2010inhibitor design, a series of new artificial substrates for the endogenous hydropersulfide\u2010generating enzyme, 3\u2010mercaptopyruvate sulfurtransferase (3\u2010MST) was developed. We find that the lead molecules generated GS\u2010SH, catalyzed by 3\u2010MST, permeated cells to enhance endogenous hydropersulfides, protected cells from ferroptosis, and reduced systemic inflammation in an animal model. Together, this calibrated approach to promote cell's own radical trapping antioxidants using its biosynthetic machinery to prevent ferroptosis has tremendous implications in redox biology and therapeutics.\n                  <\/jats:p>","DOI":"10.1002\/anie.4893359","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:23:55Z","timestamp":1784291035000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineered Substrates for a Sulfurtransferase Enhance Endogenous Hydropersulfides and Inhibit Ferroptosis"],"prefix":"10.1002","volume":"65","author":[{"given":"Simran M.","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Chemistry Indian Institute of Science Education and Research Pune  Pune Maharashtra 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