{
  "abstract": "This review presents a three-tiered engineering framework that systematically addresses these barriers. First, we survey chemical and sequence-based stabilization strategies, including lipidation, backbone N-methylation, and cyclization, that convert labile natural peptides into protease-resistant scaffolds. Second, moving beyond generic stabilization, we dissect the rational design of effector-inhibitory peptides, with particular emphasis on disulfide bond topology engineering as a powerful means to lock binding-competent conformations, alongside structure-guided interface optimization. Third, recognizing that purely rational design often fails to correctly fold complex topologies, we discuss complementary structure-constrained screening platforms (phage display, yeast display, and in silico docking) that exploit sequence-conformation coupling to enrich functional structures from vast libraries. Critically, we argue that these molecular-level designs can only achieve in vivo efficacy when co-integrated with delivery systems, including lipidic, polymeric, and viral carriers, which together determine bioavailability, targeting, and controlled release. By weaving these layers into a unified framework, we highlight a paradigm shift from sequential optimization toward context-aware co-design, where peptide rigidity, flexibility, affinity, and carrier compatibility are balanced against specific therapeutic or industrial contexts.",
  "abstract_shown": true,
  "affiliations": [
    "School of Biological Science and Medical Engineering, Hunan University of Technology, Zhuzhou 412007, China.",
    "Yuelushan Laboratory, Hunan Academy of Agricultural Sciences, Changsha 410125, China.",
    "Hunan Key Laboratory of Economic Crops Genetic Improvement and Integrated Utilization, School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Qijun Xie",
      "orcid": "0000-0001-6168-8994"
    },
    {
      "affs": [
        0
      ],
      "name": "Haiying Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Biao Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Li Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yang Fang",
      "orcid": "0009-0006-7536-7546"
    },
    {
      "affs": [
        2
      ],
      "name": "Lili Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Mingli Yan",
      "orcid": "0000-0003-1725-0682"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0j4dbk424cs3a.bib",
  "cited_by": 0,
  "doi": "10.3390/biology15191754",
  "fulltext_url": "https://europepmc.org/articles/PMC13663445",
  "id": "0j4dbk424cs3a",
  "issns": [
    "2079-7737"
  ],
  "landing_url": "https://europepmc.org/article/MED/42883427",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Chemical Synthesis and Analysis"
    ]
  ],
  "openalex": "W7216381712",
  "pdf_url": "https://europepmc.org/articles/PMC13663445?pdf=render",
  "pmcid": "PMC13663445",
  "pmid": "42883427",
  "published": "2026-10-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0j4dbk424cs3a.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42883427",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42883427"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Chemical Synthesis and Analysis",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Rational Design and Delivery of Engineered Peptides: Toward a Unified Framework for Structure, Screening, and Application.",
  "title_text": "Rational Design and Delivery of Engineered Peptides: Toward a Unified Framework for Structure, Screening, and Application.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/0j4dbk424cs3a",
  "venue": "Biology",
  "versions": []
}