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Homodimeric Protein-Polymer Conjugates via the Tetrazine-trans-Cyclooctene Ligation

Lorenzo, Maltish M.; Decker, Caitlin G.; Kahveci, Muhammet U.; Paluck, Samantha J.; Maynard, Heather D.


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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/53991</identifier>
  <creators>
    <creator>
      <creatorName>Lorenzo, Maltish M.</creatorName>
      <givenName>Maltish M.</givenName>
      <familyName>Lorenzo</familyName>
    </creator>
    <creator>
      <creatorName>Decker, Caitlin G.</creatorName>
      <givenName>Caitlin G.</givenName>
      <familyName>Decker</familyName>
    </creator>
    <creator>
      <creatorName>Kahveci, Muhammet U.</creatorName>
      <givenName>Muhammet U.</givenName>
      <familyName>Kahveci</familyName>
    </creator>
    <creator>
      <creatorName>Paluck, Samantha J.</creatorName>
      <givenName>Samantha J.</givenName>
      <familyName>Paluck</familyName>
    </creator>
    <creator>
      <creatorName>Maynard, Heather D.</creatorName>
      <givenName>Heather D.</givenName>
      <familyName>Maynard</familyName>
      <affiliation>Univ Calif Los Angeles, Dept Chem &amp; Biochem, Los Angeles, CA 90095 USA</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Homodimeric Protein-Polymer Conjugates Via The Tetrazine-Trans-Cyclooctene Ligation</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2016</publicationYear>
  <dates>
    <date dateType="Issued">2016-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/53991</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1021/acs.macromol.5b02323</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">Tetrazine end-functionalized telechelic polymers were synthesized by controlled radical polymerization (CRP) and employed to generate T4 lysozyme homodimers. Mutant T4 lysozyme (V131C), containing a single surface-exposed cysteine, was modified with a protein-reactive trans-cyclooctene (T4L-TCO). Reversible addition-fragmentation chain transfer (RAFT) polymerization yielded poly(N-isopropylacrylamide) (pNIPAAm) with a number-average molecular weight (Mn by 1H NMR) of 2.0 kDa and a dispersity (D by GPC) of 1.05. pNIPAAm was then modified at both ends by postpolymerization with 6-methyltetrazine. For comparison, 2.0 kDa bis-tetrazine poly(ethylene glycol) (PEG) and 2.0 kDa bis-maleimide pNIPAAm were synthesized. Ligation of T4L-TCO to bis-tetrazine pNIPAAm or bis-tetrazine PEG resulted in protein homodimer in 38% yield and 37% yield, respectively, after only 1 h, whereas bis-maleimide pNIPAAm resulted in only 5% yield of dimer after 24 h. This work illustrates the advantage of employing tetrazine ligation over maleimide thiol-ene chemistry for the synthesis of protein homodimer conjugates.</description>
  </descriptions>
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