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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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{
  "DOI": "10.1021/acs.macromol.5b02323", 
  "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.", 
  "author": [
    {
      "family": "Lorenzo", 
      "given": " Maltish M."
    }, 
    {
      "family": "Decker", 
      "given": " Caitlin G."
    }, 
    {
      "family": "Kahveci", 
      "given": " Muhammet U."
    }, 
    {
      "family": "Paluck", 
      "given": " Samantha J."
    }, 
    {
      "family": "Maynard", 
      "given": " Heather D."
    }
  ], 
  "container_title": "MACROMOLECULES", 
  "id": "53991", 
  "issue": "1", 
  "issued": {
    "date-parts": [
      [
        2016, 
        1, 
        1
      ]
    ]
  }, 
  "page": "30-37", 
  "title": "Homodimeric Protein-Polymer Conjugates via the Tetrazine-trans-Cyclooctene Ligation", 
  "type": "article-journal", 
  "volume": "49"
}
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