Journal article Open Access

PNA-Based Dynamic Combinatorial libraries (PDCL) and screening of lectins

Lluc Farrera-Soler; Jean-Pierre Daguer; Patrick Raunft; Anne Imberty; Sofia Barluenga; Nicolas Winssinger


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  <identifier identifierType="DOI">10.5281/zenodo.3712677</identifier>
  <creators>
    <creator>
      <creatorName>Lluc Farrera-Soler</creatorName>
      <affiliation>University of Geneva</affiliation>
    </creator>
    <creator>
      <creatorName>Jean-Pierre Daguer</creatorName>
      <affiliation>University of Geneva</affiliation>
    </creator>
    <creator>
      <creatorName>Patrick Raunft</creatorName>
      <affiliation>University of Geneva</affiliation>
    </creator>
    <creator>
      <creatorName>Anne Imberty</creatorName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0001-6825-9527</nameIdentifier>
      <affiliation>Université Grenoble Alpes</affiliation>
    </creator>
    <creator>
      <creatorName>Sofia Barluenga</creatorName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0003-3830-1178</nameIdentifier>
      <affiliation>University of Geneva</affiliation>
    </creator>
    <creator>
      <creatorName>Nicolas Winssinger</creatorName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0003-1636-7766</nameIdentifier>
      <affiliation>University of Geneva</affiliation>
    </creator>
  </creators>
  <titles>
    <title>PNA-Based Dynamic Combinatorial libraries (PDCL) and screening of lectins</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2020</publicationYear>
  <dates>
    <date dateType="Issued">2020-03-17</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/3712677</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsVersionOf">10.5281/zenodo.3712676</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="https://creativecommons.org/licenses/by/4.0/legalcode">Creative Commons Attribution 4.0 International</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;Selection from dynamic combinatorial libraries (DCL) benefit from the dynamic nature of the library that can change constitution upon addition of a selection pressure, such as ligands binding to a protein. This technology has been predominantly used with small molecules interacting with each other through reversible covalent interaction. However, application of this technology in biomedical research and drug discovery has been limited by the reversibility of covalent exchange and the analytical deconvolution of small molecule fragments.&amp;nbsp;&amp;nbsp; Here we report a supramolecular approach based on the use of a constant short PNA tag to direct the combinatorial pairing of fragment.&amp;nbsp; This PNA tag yields fast exchange kinetics, while still delivering the benefits of cooperativity, and provides favourable properties for analytical deconvolution by MALDI.&amp;nbsp; A selection of &amp;gt; 6 000 assemblies of glycans (mono-, di-, tri-saccharides) targeting AFL, a lectin from pathogenic fungus, yielded a 95 nM assembly, nearly three orders of magnitude better affinity than the corresponding glycan alone (41 &amp;micro;M).&lt;/p&gt;</description>
  </descriptions>
  <fundingReferences>
    <fundingReference>
      <funderName>Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/501100001711</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/SNSF/Project+funding/200020_169141/">200020_169141</awardNumber>
      <awardTitle>Probes for chemical biology: from synthesis to biosupramolecular systems</awardTitle>
    </fundingReference>
  </fundingReferences>
</resource>
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