Biomacromolecules. 2018 Oct 8;19(10):4044-4051. doi: 10.1021/acs.biomac.8b01064. Epub 2018 Sep 20.
Protein-polymer conjugates are powerful combinations of the biotic and abiotic worlds that impact many industries. Predicting the site and impact of polymer growth from the surface of proteins is only useful if we can use that information to choose which site to modify synthetically. We have explored the combination of a predictive algorithm with a unique stepwise atom-transfer radical polymerization (ATRP) to selectively move the predominant modification sites around a model enzyme. Lysozyme was modified with defined stoichiometric ratios of polymerization initiators and initiation inhibitors to selectively and strategically grow poly(carboxybetaine methacrylate) polymers from different protein sites. Electrospray ionization mass spectrometry was used to examine the uniformity of the lysozyme-initiator and lysozyme-inhibitor complexes prior to polymer growth. Bioactivity of the lysozyme-polymer conjugates was examined as a function of polymer location on the enzyme surface. Step-wise atom-transfer radical polymerization from proteins provides a versatile and modular approach that can be extended to the rational and selective design of other protein-polymer conjugates.
蛋白质-聚合物缀合物是生物和非生物世界的强大组合，对许多行业都有影响。如果我们能够利用这些信息来选择要进行合成修饰的位点，那么预测聚合物从蛋白质表面生长的位置和影响才是有用的。我们探索了将预测算法与独特的逐步原子转移自由基聚合（ATRP）相结合，以有选择地围绕模型酶移动主要修饰位点。溶菌酶用聚合引发剂和引发抑制剂的确定化学计量比进行修饰，以从不同的蛋白质位点选择性和策略性地生长聚（羧基甜菜碱甲基丙烯酸酯）聚合物。在聚合物生长之前，使用电喷雾电离质谱法检查溶菌酶-引发剂和溶菌酶-抑制剂复合物的均匀性。作为酶表面聚合物位置的函数，检查了溶菌酶-聚合物缀合物的生物活性。从蛋白质进行逐步原子转移自由基聚合提供了一种通用且模块化的方法，可以扩展到其他蛋白质-聚合物缀合物的合理和选择性设计。
