低温干燥过程中LEA蛋白对胰岛素结构稳定性的研究

Investigation on Bioactive Protection of LEA Protein for Insulin by Molecular Simulation in the Low-temperature Drying Process

当前蛋白药物日益在许多疾病的诊断、预防和治疗方面表现出重要的作用。然而,蛋白药物具有热敏性的特点,其活性结构大多不够稳定。因此,研究热敏性蛋白药物的有效保护方法并探究其保护机制对热敏蛋白药物的生产、贮存和应用具有重大的研究意义和实用价值。本文选择胰岛素为热敏性蛋白药物,胚胎发育晚期丰富(LEA)蛋白为活性保护剂,通过分子模拟方法详细研究了LEA蛋白对胰岛素生物活性的保护作用。研究结果表明:与没有任何保护的胰岛素的活性三维结构相比,LEA蛋白对胰岛素活性三维结构具有良好的保护作用,而且受保护的胰岛素的二级结构也非常稳定。由此可见,LEA蛋白是一个优良的热敏蛋白药物活性保护剂。

Nowadays various protein medicines are increasingly playing significant roles in the treatment of many diseases,but the bioactive structures of such kinds of protein medicines are unstable because they are heat sensitive.Therefore,it is very important to explore a protective method and to explain the protective mechanism of protein medicines.In the present research,insulin was chosen as a heat-sensitive protein medicine,and a Group 3 late embryogenesis abundant（LEA） protein was chosen as its bioactive protectant during desiccation.The results of replica exchange molecular dynamics simulation suggest that comparing with insulin without any protection,the bioactive 3D structure and secondary structure of the insulin protected by LEA protein were preserved very well.All analyzing results proved that the LEA protein was a good bioactive protectant for heat sensitive protein medicines.