{
  "abstract": "DNA-encoded libraries (DELs) access vast chemical spaces for drug discovery, but split-and-pool DEL synthesis remains the sole and very manual portion of the DEL workflow. Here, we automate DEL construction using diethylaminoethyl-functionalized weak anion exchange (WAX) magnetic resin and a KingFisher Apex particle-handling instrument. DNA encoding occurs in solution, followed by selective immobilization of DNA conjugates under low-salt conditions that exclude > 95% of unused encoding oligonucleotides. On-DNA chemistry then proceeds using the WAX resin-adsorbed \"WAX-ON\" DNA substrate in neat organic solvent. The platform supports amide formation, reductive amination, copper-catalyzed azide-alkyne cycloaddition, and Fmoc removal. Automated bead transfer enables iterative reaction and washing cycles. We synthesized two-cycle 9,216-member DELs from 96 Fmoc-protected amino acids and 96 carboxylic acids. Control selections reproducibly enriched the carbonic anhydrase ligand sulfamoylbenzoic acid. Magnetic WAX-ON DEL synthesis is compatible with diverse chemistries and uses the same instrumentation to automate end-to-end DEL preparation and affinity screening.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Valerie Cavett",
      "orcid": "0000-0003-2859-6355"
    },
    {
      "name": "Santino L. DeGirolamo",
      "orcid": "0009-0000-0973-149X"
    },
    {
      "name": "Erika M. Cerna Arroyo",
      "orcid": "0009-0007-9401-6757"
    },
    {
      "name": "Robert Damoiseaux",
      "orcid": "0000-0002-7611-7534"
    },
    {
      "name": "Brian M. Paegel",
      "orcid": "0000-0002-6531-6693"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7rqxs353d1rcx.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.21.760614",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.21.760614v1.full",
  "id": "7rqxs353d1rcx",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.21.760614v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Chemical Synthesis and Analysis"
    ]
  ],
  "openalex": "W7223216817",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.21.760614v1.full.pdf",
  "pmcid": "PMC13738759",
  "pmid": "42996197",
  "published": "2026-10-21",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/7rqxs353d1rcx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:09Z",
      "native_id": "10.64898/2026.10.21.760614",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.21.760614v1"
    },
    {
      "first_seen": "2026-11-09T12:23:41Z",
      "native_id": "PMC13738759",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.21.760614"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Chemical Synthesis and Analysis",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Automated DNA-Encoded Library Synthesis on Magnetic Anion Exchange Resin",
  "title_text": "Automated DNA-Encoded Library Synthesis on Magnetic Anion Exchange Resin",
  "type": "preprint",
  "updated_at": "2026-11-09T12:23:41Z",
  "url": "https://research.draconitic.com/paper/7rqxs353d1rcx",
  "venue": "bioRxiv",
  "versions": []
}