| 聚乙二醇修饰胰高血糖素样肽1类似物反应条件的响应面法优化#br# |
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| 引用本文： | 秦荣浦,田石华,江筠,刘敏,张慧颖,何成,楼觉人.聚乙二醇修饰胰高血糖素样肽1类似物反应条件的响应面法优化#br#[J].国际生物制品学杂志,2020,43(3):120-125. |
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| 作者姓名： | 秦荣浦 田石华 江筠 刘敏 张慧颖 何成 楼觉人 |
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| 作者单位： | 上海生物制品研究所有限责任公司第二研究室 200051
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| 摘 要： | 目的 用响应面法对马来酰亚胺活化相对分子质量40 000的聚乙二醇（polyethylene glycol，PEG）（MAL-PEG40K）修饰胰高血糖素样肽1类似物（glucagon-like peptide-1 analog，GLP-1a）的反应条件进行优化。方法 对GLP-1a浓度、GLP-1a/MAL-PEG40K摩尔比、反应液pH值、反应温度、反应时长进行单因素试验。以前3个条件为自变量， PEG修饰率为响应值，根据中心组合试验设计原理，研究各自变量及其交互作用对PEG修饰率的影响。通过高效液相色谱法分析PEG修饰率，依据回归分析确定各反应条件的最优值。 结果 GLP-1a与MAL-PEG40K的最佳反应条件为：GLP-1a浓度2.5 mg/ml，GLP-1a/MAL-PEG40K摩尔比1∶1.25，反应液pH 8，反应温度4 ℃，反应时长60 min。该优化条件下，GLP-1a的PEG修饰率可达91.0%。结论 响应面法获得了GLP-1a与MAL-PEG40K的最佳反应条件。
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| 关 键 词： | ,胰高血糖素样肽1,聚乙烯二醇类,反应条件,响应面法, |
Response surface optimization of polyethylene glycol modification conditions for glucagon-like peptide-1 analog#br# |
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| Affiliation: | No.2 Research Laboratory, Shanghai Institute of Biological Products Co., Ltd., Shanghai 200051, China
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| Abstract: | Objective To optimize the reaction conditions of maleimide-activated polyethylene glycol (PEG)( MAL-PEG40K ) modified glucagon-like peptide-1 analog (GLP-1a) by response surface methodology. Methods Single-factor tests were performed on concentration of GLP-1a, molar ratio of GLP-1a to MAL-PEG40K, pH value of the solution, reaction temperature and reaction duration. The first 3 parameters were taken as independent variables, and the PEG modification rate was used as the response value. According to the design principle of the central combination test, the variables and their interactions were studied for influence on PEG modification rate. The PEG modification rate was analyzed by reversed-phase high performance liquid chromatography, and the optimal value of each reaction condition was determined by regression analysis. Results The optimal PEG modification conditions of GLP-1a were GLP-1a concentration of 2.5 mg/ml, GLP-1a to MAL-PEG40K molar ratio of 1:1.25, solution pH of 8, reaction temperature of 4 ℃, and duration of 60 min. Under these conditions, the PEG modification rate of GLP-1a reached 91.0%. Conclusion Using response surface methodology, the optimal reaction conditions of GLP-1a and MAL-PEG40K are obtained. |
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| Keywords: | Glucagon-like peptide 1 Polyethylene glycols Reaction conditions Response surface methodology
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