1 Ocak 2016 Dergi makalesi Açık Erişim

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

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    <subfield code="a">Homodimeric Protein-Polymer Conjugates via the Tetrazine-trans-Cyclooctene Ligation</subfield>
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    <subfield code="a">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.</subfield>
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    <subfield code="a">Kahveci, Muhammet U.</subfield>
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    <subfield code="u">Univ Calif Los Angeles, Dept Chem &amp; Biochem, Los Angeles, CA 90095 USA</subfield>
    <subfield code="a">Maynard, Heather D.</subfield>
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