{
  "abstract": "Activity-based probes are indispensable tools for interrogating protease function, and quenched fluorescent variants enable dynamic, real-time imaging of enzymatic activity. Despite these advances, very few quenched activity-based probes (qABPs) have been reported for serine proteases, which constitute the largest and most diverse mechanistic class of proteases. β-Lactams have been extensively used to develop molecular tools and drugs designed to bind or be hydrolysed by serine-dependent bacterial enzymes. Here, we report the first monocyclic β-lactam-containing qABPs for detecting serine proteases. Both the enzyme-triggered activation mechanism and intrinsic reactivity of the probes were highly dependent on the relative position of the BODIPY-FL fluorophore and quencher moiety at the β-lactam core. qABPs displaying the most efficient turn-on mechanism were shown to selectively target human neutrophil elastase (HNE) in different human cell lysates. The most successful qABP was rapidly internalised and targeted HNE in U937 cells and human neutrophils. These results demonstrate the potential of the modular β-lactam warhead to develop turn-on probes to track neutrophil serine proteases in live cells.",
  "abstract_shown": true,
  "affiliations": [
    "Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa Lisboa Portugal",
    "Faculty of Pharmacy, Universidade de Lisboa Lisboa Portugal",
    "The Francis Crick Institute 1 Midland Road London NW1 1AT UK",
    "Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela 15782 Santiago de Compostela Spain",
    "Departamento de Química Orgánica, Facultade de Farmacia, Universidade de Santiago de Compostela 15782 Santiago de Compostela Spain",
    "Fundación MEDINA Av. Conocimiento 34, Health Sciences Technology Park 18016 Granada Spain"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Rita Felix",
      "orcid": "0000-0001-7192-0822"
    },
    {
      "affs": [
        2
      ],
      "name": "Luís Carvalho"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ismael Rufino"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Rita Guedes",
      "orcid": "0000-0002-5790-9181"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ana Margarida Madureira"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Ana Mallo-Abreu",
      "orcid": "0000-0002-5092-3538"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lídia Gonçalves",
      "orcid": "0000-0002-6799-2740"
    },
    {
      "affs": [
        5
      ],
      "name": "Olga Genilloud",
      "orcid": "0000-0002-4202-1219"
    },
    {
      "affs": [
        5
      ],
      "name": "Rosario Fernandez-Godino"
    },
    {
      "affs": [
        5
      ],
      "name": "Maria C. Ramos",
      "orcid": "0000-0002-3674-615X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Rui Moreira",
      "orcid": "0000-0003-0727-9852"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/at2nknrwhgbe8.bib",
  "cited_by": 0,
  "doi": "10.1039/d6cb00206d",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733405/",
  "id": "at2nknrwhgbe8",
  "issns": [
    "2633-0679"
  ],
  "landing_url": "https://doi.org/10.1039/d6cb00206d",
  "language": "en",
  "licence": "CC-BY-3.0",
  "licence_label": "CC BY 3.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/3.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "1306|Protease and Inhibitor Mechanisms"
    ]
  ],
  "openalex": "W7140046702",
  "pdf_url": "https://pubs.rsc.org/cb/article-pdf/doi/10.1039/D6CB00206D/14968222/d6cb00206d.pdf",
  "pmcid": "PMC13733405",
  "pmid": "42985660",
  "published": "2026-10-29",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/at2nknrwhgbe8.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:11Z",
      "native_id": "PMC13733405",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6cb00206d"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Protease and Inhibitor Mechanisms",
      "subfield": "oncology"
    }
  ],
  "title": "BODIPY-tagged β-lactams as selective quenched activity-based probes to target human neutrophil elastase",
  "title_text": "BODIPY-tagged β-lactams as selective quenched activity-based probes to target human neutrophil elastase",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:11Z",
  "url": "https://research.draconitic.com/paper/at2nknrwhgbe8",
  "venue": "RSC Chemical Biology",
  "versions": []
}