{
  "abstract": "Active recruitment of host complement regulators to biomedical surfaces emerges as a therapeutic strategy to prevent adverse immuno-inflammatory reactions to biomaterials and organ transplants. Coating with the macrocyclic peptide 5C6, which binds and recruits the central complement regulator factor H (FH), was shown to protect clinically relevant surfaces from complement attack. While we previously identified general determinants for the 5C6-FH interaction, more granular structure-activity relationship (SAR) studies have hitherto been missing. In the absence of published target structures, we employed a panel of focused amino acid substitutions combined with biomolecular interaction studies to achieve an SAR profile of 5C6. We identified three positions that are particularly amenable to affinity optimization and combined several changes to produce a next-generation 5C6 analog with enhanced target residence time and serum stability. Biomaterial-related assays suggest that such analogs may confer benefits under stress conditions, providing a path for the further development of 5C6-based coatings.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmaceutical Sciences",
    "University of Basel",
    "Institute for Drug Discovery, Faculty of Medicine",
    "Leipzig University",
    "Perelman School of Medicine",
    "University of Pennsylvania"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Clément Bechtler"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jannes Felsch"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ekaterina Umnyakova"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lukas Kaufmann"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Christina Lamers"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "John D. Lambris"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Daniel Ricklin",
      "orcid": "0000-0001-6140-0233"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a750e2wqh47pw.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010149/v1",
  "fulltext_url": null,
  "id": "a750e2wqh47pw",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010149/v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Complement system in diseases"
    ]
  ],
  "openalex": "W7221130171",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/a750e2wqh47pw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.26434/chemrxiv.15010149",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010149/v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Complement system in diseases",
      "subfield": "immunology"
    }
  ],
  "title": "Structure-Activity Relationship Studies of the Complement Regulator-Recruiting Peptide 5C6",
  "title_text": "Structure-Activity Relationship Studies of the Complement Regulator-Recruiting Peptide 5C6",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:22Z",
  "url": "https://research.draconitic.com/paper/a750e2wqh47pw",
  "venue": "ChemRxiv",
  "versions": []
}