聚乙二醇修饰重组人干扰素α_(2a)的研究

Study on Modification of rhIFNα_(2a) with Polyethylene Glycol

目的 探讨聚乙二醇(mPEG-ss Mr 5000和Mr 20000)修饰重组人干扰素α2a(rhlFNα2a)的最佳反应条件。方法在不同反应条件下,用聚乙二醇修饰rhIFNα2a,采用VSV-Wish细胞病变抑制法测定修饰后rhIFNα2a的体外抗病毒活性。结果 随着PEG对rhlFNα2a摩尔比增加和修饰反应时间的延长,rhIFNα2a修饰产物相对分子质量和不均一性增加,且随着rhIFNα2a修饰度的提高,其体外抗病毒活性逐渐降低。结论 初步确立了PEG修饰rhIFNα2a的反应条件,表明反应摩尔比与聚乙二醇的相对分子量是影响反应的关键因素。

Objective To explore the optimal condition of modifying rhIFNαt2a by polyethylene glycol(PEG) with relative molecular weight of 5 000 and 20 000. Methods rhIFNα2a was modified with PEG under various conditions, and the bioactivity of the modified rhIFNα2a were analyzed by VSV - Wish system. Results Along with the increase of the ratio of PEG to rhIFNα2a as well as the reaction time, the relative molecular weight and inhomogeneity of the modified rhIENα2a were also increased. And the bioactivity of PEG - rhIFNα2a was reduced with the improvement of modification degree. Conclusion The optimal condition of modifying rhIFNα2a with activated polyethylene glycol is preliminarily determined.The molar ratio of PEG to rhIFNα2a and the relative molecular weight of PEG play important roles in the modification.