{
  "abstract": "Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder, driving the search for multitarget-directed ligands (MTDLs) able to modulate multiple pathological pathways. Since amphibians represent a rich source of bioactive peptides, skin extracts from Scinax nasicus and Dendropsophus nanus, classified by sex, developmental stage, and season, were evaluated against key AD-related mechanisms, including cholinesterase inhibition, antioxidant activity, and Fe2+ chelation. Subsequently, a rational discovery workflow was implemented, integrating extract-level chemical characterization and bioactivity screening with the sequence identification of the main components and a novel in silico algorithm-based prioritization. This strategy, formalized through the Multi-Target Therapeutic Potential Score (MTTP-Score), served as a rational filter to produce a focused synthetic library, significantly minimizing experimental time and cost. Peptides derived from D. nanus (Dn) displayed the most promising multitarget candidates. Dn-7 combined sub-micromolar dual cholinesterase inhibition (IC50 = 0.32 and 1.2 µM for AChE and BChE, respectively) with highly efficient Fe2+ chelation (EC50 = 39 µM), representing the highest MTDL activity reported for an amphibian peptide. Dn-18 emerged as a moderate butyrylcholinesterase inhibitor with strong metal chelating capacity. Overall, this study establishes a pipeline for the rational discovery of peptide-based MTDL scaffolds for AD.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratorio de Péptidos Bioactivos, Departamento de Química Orgánica, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe 3000, Argentina",
    "Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290, Ciudad Autónoma de Buenos Aires (CABA) 1425, Argentina",
    "Grupo de Estudios Sobre Anfibios, Laboratorio de Biodiversidad y Conservación de Tetrápodos, Instituto Nacional de Limnología (INALI: CONICET-UNL), Santa Fe 3000, Argentina"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Álvaro José Rietmann",
      "orcid": "0000-0003-1029-8229"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Iván Sanchis",
      "orcid": "0000-0001-6833-0813"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Roque Spinelli"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Javier Alejandro López",
      "orcid": "0000-0002-5156-6915"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Álvaro S. Siano",
      "orcid": "0000-0002-7790-5532"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6mfkemyxd6khc.bib",
  "cited_by": 0,
  "doi": "10.3390/biom16101458",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702688/?tool=EBI",
  "id": "6mfkemyxd6khc",
  "issns": [
    "2218-273X"
  ],
  "landing_url": "https://www.mdpi.com/2218-273X/16/10/1458",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2736|Cholinesterase and Neurodegenerative Diseases"
    ]
  ],
  "openalex": "W7220847863",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702688/pdf/?tool=EBI",
  "pmcid": "PMC13702688",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/6mfkemyxd6khc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:59Z",
      "native_id": "10.3390/biom16101458",
      "source": "crossref",
      "url": "https://www.mdpi.com/2218-273X/16/10/1458"
    },
    {
      "first_seen": "2026-10-30T12:21:48Z",
      "native_id": "PMC:PMC13702688",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13702688"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Cholinesterase and Neurodegenerative Diseases",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "From Amphibian Extracts to Focused Libraries: An Algorithm-Based Strategy to Uncover Potent Multi-Target Anti-Alzheimer Peptides",
  "title_text": "From Amphibian Extracts to Focused Libraries: An Algorithm-Based Strategy to Uncover Potent Multi-Target Anti-Alzheimer Peptides",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:48Z",
  "url": "https://research.draconitic.com/paper/6mfkemyxd6khc",
  "venue": "Biomolecules",
  "versions": []
}