{
  "abstract": "Targeting E3 ubiquitin ligases with chemical probes remains a major challenge, despite their central roles in cellular regulation and disease. Constitutive photomorphogenic 1 (COP1) is an E3 ligase whose complex, adaptor-dependent biology has made its selective targeting difficult. Here, we develop a peptide-based affinity selection mass spectrometry (Pep-AS-MS) platform to discover new peptide based COP1 binders. Leveraging a mass spectrometry compatible library design, fluorescence-guided selection optimisation, and an open-source software driven target-decoy database strategy for peptide identification and quantification, we enable hit ranking from highly complex combinatorial libraries. Using this approach, we identify and validate six previously unreported COP1-binding peptides, including ligands with binding potencies comparable to the native TRIB1 motif. This work establishes a quantitative and accessible Pep-AS-MS framework for ligand discovery against challenging protein–protein interaction targets and provides new chemical tools to interrogate COP1 biology.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cancer Sciences, Faculty of Medical and Health Sciences, University of Auckland 85 Park Rd, Grafton Auckland 1023 New Zealand",
    "School of Biological Sciences, University of Auckland 23 Symonds St Auckland 1010 New Zealand",
    "Maurice Wikins Centre for Molecular Biodiscovery, University of Auckland Auckland 1142 New Zealand",
    "Department of Biochemistry, University of Otago 710 Cumberland St Dunedin 9016 New Zealand",
    "Mass Spectrometry Hub, School of Biological Sciences, University of Auckland 23 Symonds St Auckland 1010 New Zealand"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Harsha Negi",
      "orcid": "0000-0003-1771-0001"
    },
    {
      "affs": [
        0
      ],
      "name": "Noor Radhi",
      "orcid": "0009-0007-3103-0914"
    },
    {
      "affs": [
        1
      ],
      "name": "Nicolas Schiff"
    },
    {
      "affs": [
        3
      ],
      "name": "Sam A. Jamieson",
      "orcid": "0000-0003-0120-4737"
    },
    {
      "affs": [
        4
      ],
      "name": "Deanna Shea"
    },
    {
      "affs": [
        4
      ],
      "name": "Martin Middleditch"
    },
    {
      "affs": [
        1
      ],
      "name": "Robert Mullin",
      "orcid": "0009-0000-0090-4286"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Renata Kowalczyk",
      "orcid": "0000-0002-0009-5869"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Paul W. Harris",
      "orcid": "0000-0002-2579-4543"
    },
    {
      "affs": [
        3,
        2
      ],
      "name": "Peter D. Mace",
      "orcid": "0000-0003-2175-9537"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Daniel Conole",
      "orcid": "0000-0002-3389-8377"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/er43gnbr6czby.bib",
  "cited_by": 0,
  "doi": "10.1039/d6cb00250a",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13586983/",
  "id": "er43gnbr6czby",
  "issns": [
    "2633-0679"
  ],
  "landing_url": "https://doi.org/10.1039/d6cb00250a",
  "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",
      "1605|Chemical Synthesis and Analysis"
    ]
  ],
  "openalex": "W7212122542",
  "pdf_url": "https://pubs.rsc.org/cb/article-pdf/doi/10.1039/D6CB00250A/13775460/d6cb00250a.pdf",
  "pmcid": "PMC13586983",
  "pmid": "42761335",
  "published": "2026-09-10",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/er43gnbr6czby.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:23:30Z",
      "native_id": "PMC13586983",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6cb00250a"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Chemical Synthesis and Analysis",
      "subfield": "organic"
    }
  ],
  "title": "Affinity selection mass spectrometry screening discovers new COP1 peptide binders",
  "title_text": "Affinity selection mass spectrometry screening discovers new COP1 peptide binders",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:20:58Z",
  "url": "https://research.draconitic.com/paper/er43gnbr6czby",
  "venue": "RSC Chemical Biology",
  "versions": []
}