Synthesis, characterization, and bioactivity of mid-functional polyHPMA-lysozyme bioconjugates

Lei Tao, Jiangtao Xu, David Anthony Gell, Thomas Paul Davis

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51 Citations (Scopus)


A thiazolidine-2-thione mid-functionalized chain transfer agent (CTA) was synthesized and used as a reversible addition-fragmentation chain transfer (RAFT) polymerization agent to prepare poly(N-(2-hydroxypropyl)methacrylamide) (polyHPMA) with mid-chain thiazolidine-2-thione functionality. The synthesized polymers were fully analyzed by 1H NMR and GPC, confirming well-defined structures (predesigned molecular weights, narrow polydispersities, and high functionalization efficiencies). A subsequent hydrolysis/analysis of the polymers was performed to verify their mid-functional structures. These mid-functionalized polymers were then incubated with a model protein (lysozyme) to generate branched polymer-protein bioconjugates. The bioactivity of the branched polymer-protein conjugate was tested and compared to similar molecular weight linear polyHPMA-protein bioconjugate; the branched polymerprotein conjugate remained much more protein activity, indicating the mid-chain-functional polyHPMA was more selective in its conjugation reaction on the lysozyme surface when compared with conjugation reactions involving terminal-functional polyHPMA. This straightforward methodology, described herein, for the synthesis of branched polymer-protein bioconjugates strikes a balance between protein protection by the attachment of polymer chains and the subsequent bioactivity retention of the bioconjugate.
Original languageEnglish
Pages (from-to)3721 - 3727
Number of pages7
Issue number8
Publication statusPublished - 2010
Externally publishedYes

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