{
  "abstract": "The blood-brain barrier (BBB) is a specialized interface that tightly regulates the exchange of molecules between the bloodstream and the brain. Its barrier function relies on a monolayer of brain endothelial cells sealed by tight junctions (TJs) that restrict paracellular flux through claudin-5 (CLDN5) multimeric complexes. To improve the delivery of nutrients and drugs to the brain, CLDN5-competitive peptides are promising carriers for creating size-controlled, temporary openings in the paracellular pathway. Here, we combine generative protein design and atomistic simulations to design ST9, a peptide with high nanomolar affinity for CLDN5. Compared with f1-C5C2, a CLDN5-binding peptide that we previously reported, ST9 induces a rapid, transient, size-controlled, and fully reversible increase in paracellular permeability, without altering CLDN5 expression or the proteomic profile of brain endothelial cells, indicating distinct mechanisms of TJ destabilization. This work provides a promising approach for developing next-generation BBB-opening agents to effectively treat neurological diseases.",
  "abstract_shown": true,
  "affiliations": [
    "Istituto Italiano di Tecnologia"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "A. Berselli"
    },
    {
      "name": "M. Trevisani"
    },
    {
      "name": "G. Alberini"
    },
    {
      "name": "A. Pastore"
    },
    {
      "name": "A. Di Fonzo"
    },
    {
      "name": "A. Armirotti"
    },
    {
      "name": "V. Castagnola"
    },
    {
      "name": "L. Maragliano"
    },
    {
      "affs": [
        0
      ],
      "name": "F. Benfenati"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7xbsz8few3n7t.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.12.751133",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.12.751133v1.full",
  "id": "7xbsz8few3n7t",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.12.751133v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2808|Barrier Structure and Function Studies"
    ]
  ],
  "openalex": "W7213561062",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.12.751133v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-12",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7xbsz8few3n7t.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:06Z",
      "native_id": "10.64898/2026.09.12.751133",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.12.751133v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Controlled Blood-Brain Barrier Modulation by a High-Affinity Claudin-5 Peptide Binder",
  "title_text": "Controlled Blood-Brain Barrier Modulation by a High-Affinity Claudin-5 Peptide Binder",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:06Z",
  "url": "https://research.draconitic.com/paper/7xbsz8few3n7t",
  "venue": "bioRxiv",
  "versions": []
}