依那西普抗体的活性结构保护

采用Gromacs软件,利用分子动力学模拟方法,研究了在真空干燥及水溶液环境下,抗体蛋白药物依那西普在不同保护剂体系中分子结构的稳定性。通过分析依那西普的结构变化以及抗体蛋白与保护剂之间的相互作用,采用单因素方差法,给出了不同保护体系与抗体蛋白之间的差异。结果表明,海藻糖–甘露醇复合保护体系和蔗糖–甘露醇复合保护体系对抗体蛋白的稳定效果明显优于海藻糖单一保护体系,其中海藻糖–甘露醇复合保护体系对依那西普抗体蛋白活性结构的保护效果最好。这说明不同的小分子保护剂可以协同保护蛋白药物的活性结构,溶剂化环境对于抗体蛋白的稳定性具有显著影响,而真空冷冻干燥可以提高其结构的稳定性。

Bioactive Structural Protection of Antibody Etanercept

The structural stability of antibody protein etanercept was studied in different protective systems, including the vacuum freeze-drying and aqueous solution environment, by using the molecular dynamics simulation method with Gromacs software. Through analyzing the structural changes of etanercept as well as the intermolecular interaction between etanercept and protectants, the significant difference between various protective systems and antibody protein was analyzed by one-factor analysis of variance. The results show that the stabilizing effect of both trehalose-mannitol complex protective system and the sucrose-mannitol complex system on antibody protein is better than that of the single trehalose system, and the trehalose-mannitol complex protective system is most effective to preserve the bioactive structure of etanercept.This indicates that the small molecule protectants can synergistically protect the bioactive structure of antibody proteins, and the solvent environment has a significant effect on the stability of antibody proteins, while the vacuum freeze-drying can improve the stability of their bioactive structure.