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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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<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Lorenzo, Maltish M.</dc:creator>
  <dc:creator>Decker, Caitlin G.</dc:creator>
  <dc:creator>Kahveci, Muhammet U.</dc:creator>
  <dc:creator>Paluck, Samantha J.</dc:creator>
  <dc:creator>Maynard, Heather D.</dc:creator>
  <dc:date>2016-01-01</dc:date>
  <dc:description>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.</dc:description>
  <dc:identifier>https://aperta.ulakbim.gov.trrecord/53991</dc:identifier>
  <dc:identifier>oai:zenodo.org:53991</dc:identifier>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>http://www.opendefinition.org/licenses/cc-by</dc:rights>
  <dc:source>MACROMOLECULES 49(1) 30-37</dc:source>
  <dc:title>Homodimeric Protein-Polymer Conjugates via the Tetrazine-trans-Cyclooctene Ligation</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
</oai_dc:dc>
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