{
  "abstract": "Cell-surface thiols are redox-sensitive functional groups that regulate cellular signalling, surface reactivity, and thiol-mediated uptake. However, these thiols are highly susceptible to irreversible oxidation during oxidative surface modification procedures, compromising cell viability and functionalization precision. Here, we report a reversible and biocompatible thiol protection strategy using sulfide tetrazines that covalently mask exofacial thiols on live cells via rapid nucleophilic aromatic substitution. This masking renders the thiols inert to oxidative damage, as demonstrated in both polymeric membranes and viable Jurkat and HeLa cells, where tetrazine-treated surfaces resisted NaIO4− induced thiol oxidation. Importantly, the protection is readily reversed by extracellular treatment with glutathione, thus restoring native thiols via nucleophilic aromatic substitution. Furthermore, we show that tetrazine-based protection preserves thiol-mediated cellular uptake capabilities, enabling precise temporal control over cell-surface thiol reactivity. This bio-protection strategy extends the toolkit of bioorthogonal chemistry to conditional masking of thiols, opening new avenues for dynamic cell-surface engineering, redox biology investigations, and controlled bioconjugation strategies in complex cellular environments.",
  "abstract_shown": true,
  "affiliations": [
    "Radboud University Nijmegen, Institute for Molecules and Materials Heyendaalseweg 135 6525 AJ Nijmegen The Netherlands"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mingchen Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Katerina Gavriel"
    },
    {
      "affs": [
        0
      ],
      "name": "Chenxuan Wan"
    },
    {
      "affs": [
        0
      ],
      "name": "Jelte Schermer"
    },
    {
      "affs": [
        0
      ],
      "name": "Kevin Neumann",
      "orcid": "0000-0002-6683-0774"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniela A. Wilson",
      "orcid": "0000-0002-8796-2274"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6nm682m2by4h3.bib",
  "cited_by": 0,
  "doi": "10.1039/d6sc04306b",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730538/?tool=EBI",
  "id": "6nm682m2by4h3",
  "issns": [
    "2041-6520",
    "2041-6539"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13730538",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "1605|Click Chemistry and Applications"
    ]
  ],
  "openalex": "W7225182226",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730538/pdf/?tool=EBI",
  "pmcid": "PMC13730538",
  "pmid": "42979595",
  "published": "2026-11-03",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/6nm682m2by4h3.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:46Z",
      "native_id": "PMC:PMC13730538",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13730538"
    },
    {
      "first_seen": "2026-11-07T12:23:04Z",
      "native_id": "PMC13730538",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6sc04306b"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Click Chemistry and Applications",
      "subfield": "organic"
    }
  ],
  "title": "Tetrazine-based bio-protection: reversible masking of cell surface thiols for orthogonal cellular chemistry",
  "title_text": "Tetrazine-based bio-protection: reversible masking of cell surface thiols for orthogonal cellular chemistry",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:23:04Z",
  "url": "https://research.draconitic.com/paper/6nm682m2by4h3",
  "venue": "Chemical science",
  "versions": []
}