{
  "abstract": "The Mannose Receptor (CD206) is a critical endocytic receptor involved in immune regulation and various pathologies, yet it remains largely unexplored as a therapeutic target due to the lack of specific modulators. We recently reported that multivalent SO 4 -3-Galactose (SO 4 -3-Gal) glycopolymers inhibit CD206 by blocking its recycling to the cell surface, but the role of ligand valency in this process was undefined. Here, using a monovalent SO4-3-Gal ligand together with a library of SO 4 -3-Gal glycopolymers spanning valencies from 6.5 to 211 – the latter synthesised via a new, scalable, metal-free aqueous RAFT route amenable to multigram production – we establish for the first time a quantitative, biphasic relationship between valency and CD206 inhibitory potency, with a steep increase up to a valency of ~28 SO 4 -3-Gal units followed by a shallower plateau, which may suggest a threshold-dependent, ligandinduced receptor clustering mechanism. Critically, these glycopolymers are non-cytotoxic, leave LPS-induced macrophage cytokine production (IL-6, IL-10, TNF-α) unaltered, and – as shown by bulk RNA sequencing of human macrophages – induce no detectable changes to the macrophage transcriptome, at baseline or upon LPS stimulation, demonstrating that CD206 blockade occurs without detectable perturbation of macrophage inflammatory responses or transcriptional profiles under the conditions tested.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, Padova, Italy, 35131",
    "School of Pharmacy",
    "University of Nottingham",
    "Department of Chemistry",
    "University of Warwick",
    "School of Medicine",
    "University of Central Lancashire",
    "Department of Surgery, Oncology and Gastroenterology, University of Padova, Via V. Gallucci 3, Padova, Italy, 35121",
    "School of Life Sciences"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Francesca Mastrotto"
    },
    {
      "affs": [
        0
      ],
      "name": "Greta Bellio"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Alexandre Blanchard"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Gokhan Yilmaz"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Sirina Muntaka"
    },
    {
      "affs": [
        7
      ],
      "name": "Enrico Gaffo"
    },
    {
      "affs": [
        7
      ],
      "name": "Stefania Bortoluzzi"
    },
    {
      "affs": [
        8,
        2
      ],
      "name": "Joshua Petch"
    },
    {
      "affs": [
        8,
        2
      ],
      "name": "David Onion"
    },
    {
      "affs": [
        8,
        2
      ],
      "name": "Darryl Jackson"
    },
    {
      "affs": [
        8,
        2
      ],
      "name": "Luisa Martinez-Pomares"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Giuseppe Mantovani",
      "orcid": "0000-0002-0837-0351"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f78w338annrt0.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15009464/v1",
  "fulltext_url": null,
  "id": "f78w338annrt0",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009464/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1605|Carbohydrate Chemistry and Synthesis"
    ]
  ],
  "openalex": "W7214349784",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009464/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/f78w338annrt0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:21Z",
      "native_id": "10.26434/chemrxiv.15009464",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009464/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Carbohydrate Chemistry and Synthesis",
      "subfield": "organic"
    }
  ],
  "title": "Multivalent SO4-3-Galactose Glycopolymers Define a Structural Threshold for CD206 Endocytic Inhibition",
  "title_text": "Multivalent SO4-3-Galactose Glycopolymers Define a Structural Threshold for CD206 Endocytic Inhibition",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:21Z",
  "url": "https://research.draconitic.com/paper/f78w338annrt0",
  "venue": "ChemRxiv",
  "versions": []
}