{
  "abstract": "Hyaluronic acid (HA) is a polysaccharide with diverse clinical and industrial applications. One of the key challenges is its sensitivity to enzymatic degradation. Chemical modifications offer a potential for modulating enzymatic susceptibility, as well as other functional properties. We report an NMR-based examination of the effect of HA modifications on hyaluronidase degradation. Chemical modification of HA with dopamine (HADN) has been widely reported, based on 1-ethyl-3-(3 dimethylaminopropyl) carbodiimide hydrochloride (EDC) chemistry. We describe a 1H NMR strategy for a convenient and sensitive analysis of hyaluronidase degradation rates. Surprisingly, HADN exhibited a degradation profile nearly identical to that of native HA, while methacrylated HA resisted degradation. The finding that HADN showed no protective effect prompted a rigorous re-investigation of HADN using 2D NMR. Our findings revealed that HADN is not a covalent conjugate, but a non-covalent and reversible system involving an unexpected EDC-dopamine adduct. Thermal and alkaline stress facilitate the release of dopamine from the non-covalent HADN complex. Our data highlight risks in the use of EDC-based conjugation experiments applied to many types of polysaccharides. Our NMR methods provide a robust platform for the dynamic comparison of degradation rates of HA, and identify a fingerprint test for characteristic residual EDC adducts.",
  "abstract_shown": true,
  "affiliations": [
    "Zernike Institute for Advanced Materials, Faculty of Science and Engineering, University of Groningen, Nijenborgh 3, Groningen, Netherlands, 9747 AG",
    "Stratingh Institute of Chemistry, Faculty of Science and Engineering, University of Groningen, Nijenborgh 3, Groningen, Netherlands, 9747 AG"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xingang Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Derk J. Wiersma"
    },
    {
      "affs": [
        0
      ],
      "name": "Alessia Lasorsa"
    },
    {
      "affs": [
        1
      ],
      "name": "Pieter van der Meulen"
    },
    {
      "affs": [
        0
      ],
      "name": "Adrivit Mukherjee"
    },
    {
      "affs": [
        0
      ],
      "name": "Patrick C.A. van der Wel",
      "orcid": "0000-0002-5390-3321"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a10mvanm3d05c.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15009034/v1",
  "fulltext_url": null,
  "id": "a10mvanm3d05c",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009034/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",
      "1307|Proteoglycans and glycosaminoglycans research"
    ]
  ],
  "openalex": "W7213551536",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009034/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/a10mvanm3d05c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:19Z",
      "native_id": "10.26434/chemrxiv.15009034",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009034/v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Proteoglycans and glycosaminoglycans research",
      "subfield": "cell-biology"
    }
  ],
  "title": "Unmasking the Non-Covalent Nature of HA–Dopamine Assemblies: Insights from 1H NMR Degradation Tracking and Multidimensional NMR",
  "title_text": "Unmasking the Non-Covalent Nature of HA–Dopamine Assemblies: Insights from 1H NMR Degradation Tracking and Multidimensional NMR",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:19Z",
  "url": "https://research.draconitic.com/paper/a10mvanm3d05c",
  "venue": "ChemRxiv",
  "versions": []
}