【摘要】 目的:提高聚乙二醇（PEG）修饰重组人改构白介素11（interleukin 11 mutein,mIL-11）反应中的单位点修饰率。方法:在考察pH、蛋白浓度、PEG与蛋白的配比等单因素对单位点修饰率影响的基础上,采用DoE设计对修饰工艺参数进行优化并建立响应最大化预测模型。结果:在pH 8. 2,mIL-11浓度0. 8 mg·mL^-1,mPEG-SC:mIL-11（摩尔比） 5. 5,修饰温度2～8℃,修饰时间1 h的条件下,单位点修饰率最大可达到53%。结论:经3批验证实验,结果与模型预测值相符,方法可行。更多还原

【Abstract】 Objective: To improve the mono-modification rate for PEGylation of recombinant human interleukin-11 mutein （mIL-11）. Methods: The effects of pH,concentration of mIL-11 and molar ratio of m PEGSC/mIL-11 on the yield of mono-PEGylated mIL-11 were investigated. Based on this,the optimization of technological parameters for PEGylation was carried out by Design of Experiment （DoE） and maximum response model was established. Results: The optimized reaction condition for the highest yield of mono-PEGylated mIL-11 was as follows:pH of 8. 2,mIL-11 concentration of 0. 8 mg·mL^-1,molar ratio of m PEG-SC/mIL-11 5. 5,and reaction time of 1 h at 2 ～ 8 ℃. Under the optimized reaction condition,a high mono-modification rate of 53% was achieved. Conclusion:The model-predicted yield was consistent with the validation experiment result by 3 batches validation.更多还原