{
  "abstract": "Covalent molecules have emerged as next-generation therapeutics and as powerful tools for perturbing fundamental biological processes. Chemical proteomic methods to screen for reactive proteinaceous amino acids have transformed small-molecule discovery pipelines, but their application remains mostly limited to sites where reactive cysteines and lysines are present. Here we report a ninhydrin-based warhead that selectively modifies arginine residues, thus expanding the repertoire of amino acids targetable by covalent molecules. Specifically, we developed alkyne-functionalized variants of ninhydrin to establish an arginine-specific chemical proteomics platform, enabling the classification of more than 6,800 unique reactive arginines from one cell line. These studies uncovered potential modification sites on disease-relevant proteins, including reactive arginines within catalytic sites that are essential for function and reactive arginines on proteins lacking reactive cysteines. By endowing a reversible small-molecule binder of cyclophilin A with a ninhydrin warhead, we achieved selective, covalent engagement in cell lysates and attenuation of enzymatic activity in vitro. These findings establish ninhydrin as a warhead for studying arginine reactivity and identifying at scale arginines amenable to covalent modification.",
  "abstract_shown": true,
  "affiliations": [
    "University of California, San Francisco , , , ,",
    "Scripps Research Institute , , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Andrew K. Ecker",
      "orcid": "0000-0001-7331-0825"
    },
    {
      "affs": [
        0
      ],
      "name": "Andreas Langen"
    },
    {
      "affs": [
        0
      ],
      "name": "Chloe S. Fields"
    },
    {
      "affs": [
        0
      ],
      "name": "José L. Montaño",
      "orcid": "0000-0002-8555-4197"
    },
    {
      "affs": [
        0
      ],
      "name": "Minh Tran"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ian B. Seiple",
      "orcid": "0000-0002-8732-1362"
    },
    {
      "affs": [
        0
      ],
      "name": "Balyn W. Zaro",
      "orcid": "0000-0002-8938-9889"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1237y4hva6gpk.bib",
  "cited_by": 1,
  "doi": "10.1021/acscentsci.6c00922",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13720922/?tool=EBI",
  "id": "1237y4hva6gpk",
  "issns": [
    "2374-7943",
    "2374-7951"
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  "landing_url": "https://pubs.acs.org/acscii/article/12/10/1610/5442588/Ninhydrin-as-a-Covalent-Warhead-for-Chemical",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
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      "lcc",
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      "openalex",
      "1605|Click Chemistry and Applications"
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  "openalex": "W7214911199",
  "pdf_url": "https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c00922",
  "pmcid": "PMC13720922",
  "pmid": "42964996",
  "published": "2026-09-01",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/1237y4hva6gpk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:37Z",
      "native_id": "10.1021/acscentsci.6c00922",
      "source": "crossref",
      "url": "https://pubs.acs.org/acscii/article/12/10/1610/5442588/Ninhydrin-as-a-Covalent-Warhead-for-Chemical"
    },
    {
      "first_seen": "2026-10-31T12:21:36Z",
      "native_id": "PMC:PMC13720922",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13720922"
    },
    {
      "first_seen": "2026-10-31T14:22:11Z",
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      "url": "https://doi.org/10.1021/acscentsci.6c00922"
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    {
      "first_seen": "2026-11-03T12:21:43Z",
      "native_id": "PMC13720922",
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      "url": "https://doi.org/10.1021/acscentsci.6c00922"
    }
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  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Click Chemistry and Applications",
      "subfield": "organic"
    }
  ],
  "title": "Ninhydrin as a Covalent Warhead for Chemical Proteomic-Enabled Discovery and Selective Engagement of Reactive Arginines",
  "title_text": "Ninhydrin as a Covalent Warhead for Chemical Proteomic-Enabled Discovery and Selective Engagement of Reactive Arginines",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:43Z",
  "url": "https://research.draconitic.com/paper/1237y4hva6gpk",
  "venue": "ACS Central Science",
  "versions": []
}