{
  "abstract": "Photoswitches can be used to optically control the bioactive conformation of molecules through E–Z photoisomerisation, thereby enabling precise regulation of biological interactions with light. Herein, we describe the first use of a photoswitchable azobispyrazole cross-linker to generate light-responsive (i, i + 7)-stapled Bak72–87 and p5317–28 peptides. Photoisomerisation (E → Z) of the stapled peptides enhanced helical content and led to an increase in binding affinity for target proteins Bcl-xL and MDM2, an effect that was reversible upon back-irradiation to the E isomer. The novel azobispyrazole cross-linker demonstrated excellent photochemical properties including near-quantitative E → Z and Z → E photoisomerisation and long thermal half-life of 65 days at 21 °C. These properties were retained in the stapled peptide form of AzBisPy-Bak72–87 (0.5-year half-life) and were tolerant to biological assay conditions. Our work expands the repertoire of photoswitches designed for peptide stapling and demonstrates the ability of azobispyrazole-stapled peptides to modulate protein–protein interactions in a system where binding is controlled exclusively by light, independent of thermal relaxation, over a timescale of several weeks.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, Molecular Sciences Research Hub, Imperial College London 82 Wood Lane London W12 0BZ UK",
    "Department of Chemistry, University of Oxford 12 Mansfield Road Oxford OX1 3TA UK",
    "Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR) 30 Biopolis Street, #07-01 Matrix Singapore 138671 Singapore"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sinead McCann"
    },
    {
      "affs": [
        1
      ],
      "name": "Davia Prischich",
      "orcid": "0000-0001-6669-0436"
    },
    {
      "affs": [
        0
      ],
      "name": "Kira Scobel"
    },
    {
      "affs": [
        0
      ],
      "name": "Dennis J. Worm"
    },
    {
      "affs": [
        0
      ],
      "name": "Aditya R. Thawani",
      "orcid": "0000-0003-0388-9055"
    },
    {
      "affs": [
        0
      ],
      "name": "Marie Mori"
    },
    {
      "affs": [
        2
      ],
      "name": "Yaw Sing Tan"
    },
    {
      "affs": [
        0
      ],
      "name": "Anna Barnard",
      "orcid": "0000-0002-1327-3417"
    },
    {
      "affs": [
        1
      ],
      "name": "Matthew J. Fuchter",
      "orcid": "0000-0002-1767-7072"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8z5hc206f3b71.bib",
  "cited_by": 0,
  "doi": "10.1039/d6sc06137k",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733666/",
  "id": "8z5hc206f3b71",
  "issns": [
    "2041-6520",
    "2041-6539"
  ],
  "landing_url": "https://doi.org/10.1039/d6sc06137k",
  "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",
      "2505|Photochromic and Fluorescence Chemistry"
    ]
  ],
  "openalex": "W7225091302",
  "pdf_url": "https://pubs.rsc.org/sc/article-pdf/doi/10.1039/D6SC06137K/14983557/d6sc06137k.pdf",
  "pmcid": "PMC13733666",
  "pmid": "42985604",
  "published": "2026-11-02",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/8z5hc206f3b71.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:23Z",
      "native_id": "PMC13733666",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6sc06137k"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:2505|Photochromic and Fluorescence Chemistry",
      "subfield": "materials-polymers"
    }
  ],
  "title": "Long-lived azobispyrazole stapled peptides for light-activated inhibition of protein–protein interactions",
  "title_text": "Long-lived azobispyrazole stapled peptides for light-activated inhibition of protein–protein interactions",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:23Z",
  "url": "https://research.draconitic.com/paper/8z5hc206f3b71",
  "venue": "Chemical Science",
  "versions": []
}