Polyethylene-glycol-modified zwitterionic polymer assisted protein aggregation arrest and refolding
Polyethylene-glycol-modified zwitterionic polymer assisted protein aggregation arrest and refolding
复制标题
聚乙二醇修饰的两性离子聚合物辅助蛋白质聚集阻滞和重折叠
DOI：
10.1039/d2me00084a
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发表时间：
2022
影响因子：
3.6
通讯作者：
Rajan Robin
中科院分区：
文献类型：
--
作者：
Debas Alisha;Matsumura Kazuaki;Rajan Robin
蛋白质聚集限制了基于蛋白质的药物的发展，并导致神经疾病。在本研究中，用聚乙二醇改性两性离子聚合物聚磺酸甜菜碱(p-SPB)，并表现出显著的抑制热诱导溶菌酶聚集的作用。研究表明，改性聚合物防止了淀粉样纤维的形成，并保留了加热后失去的溶菌酶的酶活性。聚合物的相对分子质量越大，保持酶活性的效果越好。除了这些聚合物阻止溶菌酶聚集的有效性外，进一步的评估表明，这些聚合物有助于蛋白质的复性，因为它们倾向于溶解已经形成的纤维，并恢复失去的溶菌酶活性。这些发现表明，聚乙二醇与p-SPB的融合有可能通过改变溶菌酶的疏水环境，在蛋白质分子周围创建分子屏障，从而保护蛋白质不被聚集，从而为基于蛋白质的生物药物的发展提供了空间。
Protein aggregation limits the development of protein-based drugs, and leads to neurological disorders. In this study, the zwitterionic polymer, poly-sulfobetaine (p-SPB), was modified using polyethylene glycol (PEG), and exhibited the remarkable suppression of heat-induced lysozyme aggregation. The study revealed that the modified polymers prevented the formation of amyloid fibrils, and retained the enzymatic activity of lysozyme, which is lost after heating. An increase in the molecular weight of the polymers afforded higher efficacy to perpetuate enzymatic activity. Along with the effectiveness of these polymers for lysozyme aggregation arrest, further evaluations revealed that these polymers facilitated the refolding of the protein because of their tendency to dissolve the already formed fibrils, and regained the lost lysozyme activity. These findings suggest that the amalgamation of PEG and p-SPB has the potential to protect proteins from aggregation via altering the hydrophobic environment of the lysozyme, creating a molecular shield around the protein molecules, and thus, providing scope for the development of protein-based biopharmaceuticals.