{
  "abstract": "The selective targeting of α-synuclein (α-syn) aggregates represents a critical challenge for the diagnosis and treatment of Parkinson’s disease and related synucleinopathies. While several ligands have been developed for amyloid imaging, most of them lack sufficient specificity for α-syn over other amyloid fibrils. We report here a direct-to-biology (D2B) strategy to accelerate the identification of such selective ligands. A library of 384 piperazine-derived compounds was synthesized in a plate-based format and screened to evaluate their affinity for α-syn pathogenic aggregates compared to amyloid-beta 42 (Aβ42) fibrils. Nine compounds were found to bind preferentially to α-syn aggregates, three of which displayed at least a four-fold increased binding compared to Aβ42. Further validation of those molecules using in vitro α-syn fibrils enabled to determine a new potent selective binder of fibrillar α-syn with moderate affinity (181 nM). These findings validate the potential of D2B approaches to accelerate specific ligand development for pathogenic protein aggregates.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Gaëtan Ossard"
    },
    {
      "name": "Clémentine Pescheteau"
    },
    {
      "name": "Timothée D’Anfray"
    },
    {
      "name": "David-Alexandre Buisson"
    },
    {
      "name": "Jean-Christophe Cintrat"
    },
    {
      "name": "Ronald Melki",
      "orcid": "0000-0003-0000-7096"
    },
    {
      "name": "Eugénie Romero",
      "orcid": "0000-0003-0484-1221"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9wyartz6twvkh.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15008497/v1",
  "fulltext_url": null,
  "id": "9wyartz6twvkh",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008497/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",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7211949283",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15008497/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-08",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/9wyartz6twvkh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.26434/chemrxiv.15008497",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008497/v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "Direct-to-biology approach for the selective identification of ligands for alpha-synuclein aggregates",
  "title_text": "Direct-to-biology approach for the selective identification of ligands for alpha-synuclein aggregates",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:17Z",
  "url": "https://research.draconitic.com/paper/9wyartz6twvkh",
  "venue": "ChemRxiv",
  "versions": []
}