{"entity": "publication", "iuid": "3bdd256ed73647d08ab01279d69da0c0", "timestamp": "2026-09-30T22:59:12.476Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3bdd256ed73647d08ab01279d69da0c0.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3bdd256ed73647d08ab01279d69da0c0"}}, "title": "Force-Triggered Thermodynamically Uphill Disulfide Reduction through Sulfur Oxidation State Control.", "authors": [{"family": "Mora", "given": "Marc", "initials": "M"}, {"family": "Cohen", "given": "Georgia", "initials": "G"}, {"family": "Cranton", "given": "William", "initials": "W"}, {"family": "Anton", "given": "Olaia", "initials": "O"}, {"family": "Beedle", "given": "Amy E M", "initials": "AEM"}, {"family": "Stirnemann", "given": "Guillaume", "initials": "G", "orcid": "0000-0002-5631-5699", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/be4e6f9543ad4ea6b03262c422dda952.json"}}, {"family": "Garcia-Manyes", "given": "Sergi", "initials": "S", "orcid": "0000-0001-5140-2606", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5327a9d82e914cdeb21ec08b420dec84.json"}}], "type": "journal article", "published": "2025-10-15", "journal": {"title": "Journal of the American Chemical Society", "issn": "1520-5126", "volume": "147", "issue": "41", "pages": "37701-37707", "issn-l": "0002-7863"}, "abstract": "In addition to thermal energy, current, and light, mechanical forces activate chemical reactions, often steering reaction pathways that result in products different from those obtained under thermodynamic control. Single-molecule mechanochemistry experiments have probed how the forced activation of a single covalent bond results in accelerated scission of both homolytic and heterolytic bonds, and the ring-opening of strained mechanophores in long polymers. Due to its mechanistic simplicity, the concerted SN2 thiol-disulfide nucleophilic substitution has been successfully used as a model system to interrogate how the nucleophilicity of an attacking organic, low-oxidation state thiol determines the force dependency of the thiol/disulfide exchange rate. Inorganic sulfur-oxyanions are comparatively much less reactive. Whether mechanical forces can activate the rupture of a protein disulfide by sulfur-oxyanions featuring higher oxidation states remains unknown. Here we employ single-molecule force-clamp spectroscopy, complemented by density functional theory (DFT) calculations and colorimetric assay measurements, to show that the thermodynamically nonfavored reduction of a disulfide bond by inorganic oxyanions can be activated by mechanical force. Occurring within the core of a protein with a physiological mechanical role, the force-unlocked reactivity has a direct impact on protein elasticity.", "doi": "10.1021/jacs.5c13084", "pmid": "41032857", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12532186"}], "notes": [], "created": "2026-09-23T13:24:38.189Z", "modified": "2026-09-23T13:24:38.307Z"}