{
  "abstract": "Protein cages provide useful scaffolds for nanoscale engineering because of their highly ordered structures and in vivo self-assembly. These scaffolds are amenable to late-stage conjugation, enabling an expansion in functionality. However, many conjugation techniques either lack site selectivity, require unnatural amino acid incorporation, or have bulky recognition motifs to facilitate ligation reactions. Here, an asparaginyl endopeptidase (AEP) enzyme with ligase activity is employed for the highly efficient functionalization of virus-like particles (VLPs) from Enterobacteria phage P22. The capacity of this enzyme to conjugate peptides and proteins onto assembled P22 VLPs under mild reaction conditions via a minimal extension to the P22 coat protein C-terminus is demonstrated. We extend the reaction efficiency to facilitate a one-pot dual-functionalization reaction, in which two therapeutically relevant receptor-targeting domains are conjugated to P22 VLPs in a single step. Finally, we demonstrate the potential for AEP-mediated bioconjugation to bestow P22 VLPs with receptor-binding functionality in vitro. This work demonstrates the efficacy of AEP ligases as bioconjugation tools for the site-selective functionalization of large molecular assemblies such as VLPs.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland4072, Australia.",
    "Australian Institute for Bioengineering and Nanotechnology, ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals, The University of Queensland, Brisbane, Queensland4072, Australia.",
    "Centre for Cell Factories and Biopolymers, Institute for Biomedicine and Glycomics, Australian Research Council Centre of Excellence in Synthetic Biology, Griffith University, Nathan, Queensland4111, Australia."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Maxim D Harding"
    },
    {
      "affs": [
        0
      ],
      "name": "Mark A Jackson"
    },
    {
      "affs": [
        0
      ],
      "name": "Kuok Yap",
      "orcid": "0000-0002-9409-5287"
    },
    {
      "affs": [
        1
      ],
      "name": "Pie Huda",
      "orcid": "0000-0002-2197-4993"
    },
    {
      "affs": [
        0
      ],
      "name": "David J Craik",
      "orcid": "0000-0003-0007-6796"
    },
    {
      "affs": [
        2
      ],
      "name": "Frank Sainsbury",
      "orcid": "0000-0001-8152-3820"
    },
    {
      "affs": [
        0
      ],
      "name": "Nicole Lawrence",
      "orcid": "0000-0002-9013-1770"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5mw9maz31ybv4.bib",
  "cited_by": 1,
  "doi": "10.1021/acs.bioconjchem.6c00356",
  "fulltext_url": "https://europepmc.org/articles/PMC13587598",
  "id": "5mw9maz31ybv4",
  "issns": [
    "1043-1802",
    "1520-4812"
  ],
  "landing_url": "https://europepmc.org/article/MED/42915466",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Biochemical and Structural Characterization"
    ]
  ],
  "openalex": "W7167268241",
  "pdf_url": "https://europepmc.org/articles/PMC13587598?pdf=render",
  "pmcid": "PMC13587598",
  "pmid": "42915466",
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5mw9maz31ybv4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42915466",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42915466"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Biochemical and Structural Characterization",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Selective and Efficient Functionalization of P22 Virus-Like Particles Using an Asparaginyl Ligase.",
  "title_text": "Selective and Efficient Functionalization of P22 Virus-Like Particles Using an Asparaginyl Ligase.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/5mw9maz31ybv4",
  "venue": "Bioconjugate chemistry",
  "versions": []
}