{
  "abstract": "The increasing prevalence of antimicrobial resistance and endotoxin-mediated inflammation highlights the need for alternative therapeutic strategies that combine antibacterial and immunomodulatory functions. Although cathelicidin LL-37 exhibits potent antimicrobial and lipopolysaccharide (LPS)-neutralizing activity, its clinical application is limited by cytotoxicity and high production costs. A hybrid peptide, LL37-TP5, was designed by fusing the active LPS-binding region of LL-37 (residues 13–36) with the immunomodulatory penta peptide thymopentin (TP5) to enhance endotoxin-neutralizing activity while reducing host cytotoxicity. Bioinformatics analyses predicted that LL37-TP5 adopt amphipathic α-helical structure with optimized hydrophobicity and a strong net positive (+9) charge. The hybrid peptide was successfully expressed recombinantly in Pichia pastoris (P. pastoris) and purified by Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC), yielding approximately 20.5 mg/L with 95.2% purity, consistent with in silico predictions. Considering the increasing prevalence of antimicrobial resistance in poultry production, the antibacterial activity of LL37-TP5 was evaluated against major poultry-associated bacterial pathogens. LL37-TP5 exhibited broad-spectrum antibacterial activity against Gram-negative and Gram-positive bacteria, with low minimum inhibitory and bactericidal concentrations. Furthermore, the hybrid peptide showed enhanced LPS-neutralizing activity and significantly suppressed nitric oxide and pro-inflammatory cytokine (IL-6, TNF-α, and IL-1β) production in LPS-stimulated RAW264.7 macrophages. Importantly, LL37-TP5 demonstrated markedly reduced cytotoxicity and negligible hemolytic activity compared with parental LL-37. Collectively, our findings indicate that hybridization of LL-37 with TP5 generated a peptide with favorable antimicrobial, endotoxin-neutralizing, and anti-inflammatory properties together with an improved safety profile compared with native LL-37.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Baseer Ahmad"
    },
    {
      "name": "Kiran Khurshid"
    },
    {
      "name": "Wei Xubiao"
    },
    {
      "name": "Kashif Hussain"
    },
    {
      "name": "Muhammad Asif Raza"
    },
    {
      "name": "Haizhou Gong"
    },
    {
      "name": "Christina Hölzel"
    },
    {
      "name": "Si Dayong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f92d2xje33257.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1886263",
  "fulltext_url": null,
  "id": "f92d2xje33257",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1886263",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "medicine/pharmacology-toxicology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/f92d2xje33257.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:20:50Z",
      "native_id": "10.3389/fphar.2026.1886263",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1886263"
    },
    {
      "first_seen": "2026-11-04T12:21:43Z",
      "native_id": "10.3389/fphar.2026.1886263",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1886263/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/pharmacology-toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Engineering a multifunctional LL37-TP5 hybrid peptide with potent antimicrobial endotoxin-neutralizing and anti-inflammatory properties",
  "title_text": "Engineering a multifunctional LL37-TP5 hybrid peptide with potent antimicrobial endotoxin-neutralizing and anti-inflammatory properties",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T00:21:25Z",
  "url": "https://research.draconitic.com/paper/f92d2xje33257",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}