{
  "abstract": "The bombesin family G protein-coupled receptor (GPCR), BB3, is an orphan GPCR linked to obesity and cancer. Limited selective chemical tools are available and only one high-affinity selective antagonist, Bantag-1, has been reported. Commercial supply of Bantag-1 has been sporadic, so we sought to develop an in-house synthesis pipeline of Bantag-1 to enable further BB3 research. Herein, we report the successful synthesis and pharmacological characterisation of Bantag-1 and a very focused structure-activity investigation. Pharmacological characterisation confirms the antagonistic properties of the synthesised peptide and provides insight into the possible contribution of the chosen counterion to storage stability. In GCaMP-based Ca2+ assays, the active synthesised peptide exhibited competitive antagonism of BAG-1-mediated BB3 signalling with a mean pA2 of 8.97, and a non-competitive antagonist profile against MK5046. Targeted structure-activity investigations further identified the C-terminal quaternary amine of Bantag-1 as a crucial moiety for antagonist activity, which is supported by our AI-based structural modelling and conventional docking of Bantag-1 with BB3. Together, we provide a practical synthetic route to the BB3 antagonist Bantag-1, establish key determinants of its activity and stability, and offer a structural framework for the rational design of next-generation BB3 chemical probes.",
  "abstract_shown": true,
  "affiliations": [
    "School of Chemistry",
    "University of New South Wales (UNSW",
    "School of Biomedical Sciences",
    "Skaggs School of Pharmacy and Pharmaceutical Sciences",
    "University of California San Diego"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Joshua Andrew Nillama"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Mariah R. Stavrou"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Olivia A. Clink"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Lilian Spock"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Tyler Hurlimann"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Irina Kufareva"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Nicola J. Smith"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Luke Hunter",
      "orcid": "0000-0002-8678-3602"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e25qv5qv6z7e1.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010357/v1",
  "fulltext_url": null,
  "id": "e25qv5qv6z7e1",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010357/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": "W7221601474",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010357/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-13",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/e25qv5qv6z7e1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:24Z",
      "native_id": "10.26434/chemrxiv.15010357",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010357/v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Chemical Synthesis and Analysis",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Synthesis and focused structure-activity investigation of the BB3 receptor antagonist, Bantag-1",
  "title_text": "Synthesis and focused structure-activity investigation of the BB3 receptor antagonist, Bantag-1",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:24Z",
  "url": "https://research.draconitic.com/paper/e25qv5qv6z7e1",
  "venue": "ChemRxiv",
  "versions": []
}