LEA-motif对胰岛素在低温干燥过程中活性保护的研究

Investigation on bioactive protection of LEA-motif to insulin during desiccation

摘要: 选用LEA蛋白特征重复片段（LEA-motif）作为干燥活性保护剂,以胰岛素为研究对象,研究该天热保护剂对热敏性胰岛素的干燥保护效果和作用机理。模拟采用Gromacs软件及Gromos96（53a6）简化原子力场,并采用REMD广泛采样分子模拟方法。研究结果表明,LEA蛋白特征重复片段对胰岛素的三维活性结构、二级结构都有良好的保护作用。另外,从实验验证结果可知,有LEA-motif保护的胰岛素六聚体活性明显提高。综上可知,LEA蛋白特征重复片段对热敏性蛋白药物有良好的干燥活性保护作用。

Abstract: In the paper, insulin was taken as the model of heat-sensitive drugs, and LEA-motif as the bioactive protectant. Gromacs software with Gromos96 ( 53a6) forcefield was adopted to investigate the LEA- motif protective effects on insulin by REMD molecular simulation method. Results showed a significant protective effect on 3D structure and secondary structure of insulin with the presence of LEA- motif. In addition, the potency experiment by HPLC showed the bioactivity of the rehydrated insulin with LEA-motif was higher than that of the rehydrated insulin without any protectant. In a word, LEA-motif had shown its great application value as a drying protectant for heat-sensitive protein drugs.