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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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{
  "@context": "https://schema.org/", 
  "@id": 53991, 
  "@type": "ScholarlyArticle", 
  "creator": [
    {
      "@type": "Person", 
      "name": "Lorenzo, Maltish M."
    }, 
    {
      "@type": "Person", 
      "name": "Decker, Caitlin G."
    }, 
    {
      "@type": "Person", 
      "name": "Kahveci, Muhammet U."
    }, 
    {
      "@type": "Person", 
      "name": "Paluck, Samantha J."
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA", 
      "name": "Maynard, Heather D."
    }
  ], 
  "datePublished": "2016-01-01", 
  "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.", 
  "headline": "Homodimeric Protein-Polymer Conjugates via the Tetrazine-trans-Cyclooctene Ligation", 
  "identifier": 53991, 
  "image": "https://aperta.ulakbim.gov.tr/static/img/logo/aperta_logo_with_icon.svg", 
  "license": "http://www.opendefinition.org/licenses/cc-by", 
  "name": "Homodimeric Protein-Polymer Conjugates via the Tetrazine-trans-Cyclooctene Ligation", 
  "url": "https://aperta.ulakbim.gov.tr/record/53991"
}
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