具有不同疏水性和pH响应性的聚电解质与蛋白质的作用研究

项目名称： 具有不同疏水性和pH响应性的聚电解质与蛋白质的作用研究

项目编号： No.20874016

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 医药、卫生

项目作者： 姚萍

作者单位： 复旦大学

项目金额： 36万元

中文摘要： 通过在聚电解质上接枝不同程度的脂肪族侧链或者胆酸基团，以及在主链上连接部分疏水片段增加聚电解质的疏水性，我们利用聚电解质疏水性的变化和羧基/氨基的pH响应性质调控聚电解质在不同pH、离子强度和温度条件下与蛋白质的结合能力以及纳米复合物胶束的形成和解离，研究了蛋白质在不同条件下从复合物胶束中释放出来的速率以及活性和结构的变化。我们的研究结果进一步证实了疏水修饰的聚电解质可以有效地增加与蛋白质的结合效率和结合量，并且蛋白质释放以后可以完全恢复其结构和活性。除此而外，我们还得到了以下结论： 1. 疏水作用力是短程作用力，静电吸引力作为长程作用力对聚合物和蛋白质的高效结合是必要条件。2. 对聚电解质结构而言，疏水基团在主链和侧链都可以增加与蛋白质的结合能力。3. 对疏水基团而言，无论是链状结构还是平面结构都可以增加与蛋白质的结合能力。4. 无论是蛋白质还是聚合物，其疏水基团的暴露可以增加二者的结合。5. 在pH 7.4的生理条件下，蛋白质的释放速率可以通过聚合物与蛋白质之间的静电和疏水作用进行调控。本项目的实施对蛋白质药物的输送和蛋白质纯化将有所帮助。

中文关键词： 聚电解质；蛋白质；疏水作用；静电作用；蛋白质输送

英文摘要： In this project, acyclic or cholic acid groups were grafted to polyelectrolytes with different grafting degrees, or hydrophobic segments were linked in main chain to increase the hydrophobicity of the polyelectrolytes. By changing the hydrophobicity of polyelectrolytes and the charges of carboxyl and amino groups at different pH, we studied the interactions and binding between polyelectrolyte and protein at different conditions of pH, ionic strength and temperature. We also investigated the formation and dissociation of the complex particles, the release rate of the loaded protein, and the changes of the structure and activity of the protein after interacting with and releasing from the complexes. Our studies further confirmed that the hydrophobic modified polyelectrolytes can effectively increase their protein loading efficiency and loading capacity. After release, the loaded protein can completely recover the native structure and activity. Furthermore, the following conclusions can be drawn from the results of this study. 1. As hydrophobic interaction is a short range interaction, electrostatic attraction between polyelectrolyte and protein is necessary for an effective binding. 2. For the structure of polyelectrolytes, no matter the hydrophobic groups linked to main chain or side chain can increase the binding with protein. 3. For the structure of hydrophobic groups, both linear chain and facial groups can increase the interaction with protein. 4. The exposed hydrophobic groups in polyelectrolyte or protein can benefit the interaction. 5. At pH 7.4 physiological condition, the release rate of the protein from the complex is tunable by the electrostatic and hydrophobic interactions between the polyelectrolyte and protein. The knowledge gained from this study on the interactions of protein and hydrophobic modified polyelectrolyte can be applied in the fields of protein delivery and protein purification.

英文关键词： polyelectrolyte; protein; hydrophobic interaction; electrostatic interaction; protein delivery