Protein-polymer bioconjugates present a way to make enzymes more efficient and robust for industrial and medicinal applications. While much work has focused on mono-functional conjugates, that is, conjugates with one type of polymer attached such as poly(ethylene glycol) or poly(N-isopropylacrylamide), there is a practical interest in gaining additional functionality by synthesizing well-defined bifunctional conjugates in a hetero-arm star copolymer architecture with protein as the core. Using ubiquitin as a model protein, a synthetic scheme is developed to attach two different polymers (oligo(ethylene oxide) methacrylate and N,N-dimethylacrylamide) directly to the protein surface, using orthogonal conjugation chemistries and grafting-from by photochemical living radical polymerization techniques. The additional complexity arising from attempts to selectively modify multiple sites led to decreased polymerization performance and indicates that initiators for continuous activator regeneration atom transfer radical polymerization and reversible addition-fragmentation chain transfer polymerization are not well-suited to bifunctional bioconjugates applications under the studied conditions. Nonetheless, the polymerization conditions preserve the native fold of the ubiquitin and enable production of a hetero-arm star protein-polymer bioconjugate.

中文翻译：

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通过光化学接枝形成两种不同的聚合物泛素缀合物

蛋白质-聚合物生物共轭物提供了一种使酶在工业和医学应用中更高效、更稳定的方法。虽然许多工作都集中在单功能缀合物上，即与一种类型的聚合物连接的缀合物，例如聚（乙二醇）或聚（N-异丙基丙烯酰胺），但通过合成明确定义的化合物来获得额外的功能具有实际意义。以蛋白质为核心的异臂星形共聚物结构中的双功能缀合物。使用泛素作为模型蛋白质，开发了一种合成方案，利用正交共轭化学和光化学活性自由基聚合接枝，将两种不同的聚合物（寡聚（环氧乙烷）甲基丙烯酸酯和 N,N-二甲基丙烯酰胺）直接附着到蛋白质表面技术。尝试选择性修饰多个位点所产生的额外复杂性导致聚合性能下降，并表明连续活化剂再生原子转移自由基聚合和可逆加成断裂链转移聚合的引发剂不太适合所研究条件下的双功能生物缀合物应用。尽管如此，聚合条件保留了泛素的天然折叠，并能够生产异臂星形蛋白-聚合物生物缀合物。