{
  "abstract": "Nucleic acid aptamers provide a simple, cost-effective alternative to antibodies for targeting biomolecular analytes from ions to large protein complexes. However, the interactions of these nucleic-acid based structures in vivo remains largely uncharacterized. Here, we report the seemingly pervasive electrostatic association between nucleic acids and high isoelectric point proteins under biological conditions. Such non-specific binding runs the risk of convoluting aptamer selection and validation, while also potentially interfering with nucleic acid-based nanotechnologies in vivo. Through our explorations, we identify several methods to disentangle sequence-specific aptamer interactions from non-specific electrostatic association, allowing for discrimination between binding modes. We also identify dissociation rate (koff) and equilibrium binding response (Req) as potentially better discriminators than KD for isolating and validating true sequence-specific aptamers.",
  "abstract_shown": true,
  "affiliations": [
    "Chan Zuckerberg Biohub Chicago",
    "Department of Chemistry, Weinberg College of Arts & Sciences",
    "Northwestern University",
    "Department of Biomedical Engineering, McCormick School of Engineering",
    "Simpson Querrey Institute",
    "Department of Biochemistry, Feinberg School of Medicine",
    "International Institute for Nanotechnology",
    "Robert H. Lurie Comprehensive Cancer Center",
    "Ralph N. Adams Institute for Bioanalytical Chemistry",
    "University of Kansas",
    "Department of Chemistry"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Connor D. Flynn",
      "orcid": "0009-0009-5692-5719"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4,
        5,
        6,
        7
      ],
      "name": "Shana O. Kelley",
      "orcid": "0000-0003-3360-5359"
    },
    {
      "affs": [
        0,
        3,
        2,
        8,
        9,
        10
      ],
      "name": "Dingran Chang",
      "orcid": "0000-0002-3127-8668"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/axbr92vttehw8.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010585/v1",
  "fulltext_url": null,
  "id": "axbr92vttehw8",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010585/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",
      "1312|Advanced biosensing and bioanalysis techniques"
    ]
  ],
  "openalex": "W7222564310",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010585/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-16",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/axbr92vttehw8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:24Z",
      "native_id": "10.26434/chemrxiv.15010585",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010585/v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Advanced biosensing and bioanalysis techniques",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Looking Beyond KD for Aptamer Validation: Disentangling Specific Aptamer Binding from Electrostatic Association for Basic Protein Targets",
  "title_text": "Looking Beyond KD for Aptamer Validation: Disentangling Specific Aptamer Binding from Electrostatic Association for Basic Protein Targets",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:24Z",
  "url": "https://research.draconitic.com/paper/axbr92vttehw8",
  "venue": "ChemRxiv",
  "versions": []
}