{
  "abstract": "Protein solubility is a key factor of peptide and protein modification and downstream application, yet chemical functionalization under aqueous conditions often compromise solubility. Here, we introduce a new class of ionic, water-soluble isocyanides for the functionalization of peptide carboxyl groups under aqueous conditions. By combining strong hydrogen-bonding motifs with ionic functionalities, these reagents provide enhanced water solubility while enabling modulation of peptide isoelectric points. The isocyanides were synthesized via a concise route and applied successfully in Passerini multicomponent reactions without observable precipitation. The resulting esterified peptides remained water-soluble even for highly hydrophobic sequences. They also served as competent substrates for omniligase-1-mediated ligation, with polar cationic modifications showing particularly favorable performance. These results demonstrate that rational isocyanide design can overcome solubility losses associated with peptide esterification, expand the scope of isocyanide-based ligation chemistry in aqueous environments, and provide a platform for tuning protein surface charge.",
  "abstract_shown": true,
  "affiliations": [
    "Biobased Organic Chemistry, Maastricht University, Urmonderbaan 22, Geleen, Netherlands, 6167RD",
    "EnzyTag B.V., Daelderweg 9, Nuth, Netherlands, 6361HK"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "M. Lambers"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Hanssens"
    },
    {
      "affs": [
        0
      ],
      "name": "T.A.A. Combaret"
    },
    {
      "affs": [
        0
      ],
      "name": "G. Bartkiewicz"
    },
    {
      "affs": [
        1
      ],
      "name": "L. J. van den Bos"
    },
    {
      "affs": [
        0
      ],
      "name": "J. M. Saya",
      "orcid": "0000-0002-4120-8807"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/754af48rskryn.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010005/v1",
  "fulltext_url": null,
  "id": "754af48rskryn",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010005/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",
      "1312|Chemical Synthesis and Analysis"
    ]
  ],
  "openalex": "W7220831590",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010005/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-06",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/754af48rskryn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.26434/chemrxiv.15010005",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010005/v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Chemical Synthesis and Analysis",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Water-Soluble Isocyanides for Passerini-Mediated Peptide Modification and Ligation",
  "title_text": "Water-Soluble Isocyanides for Passerini-Mediated Peptide Modification and Ligation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:22Z",
  "url": "https://research.draconitic.com/paper/754af48rskryn",
  "venue": "ChemRxiv",
  "versions": []
}