胰高血糖素样肽-1在乙醇中的聚乙二醇修饰
Modification of Glucagon-like Peptide-1 in Ethanol with Polyethylene Glycol
查看参考文献14篇
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文摘
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以乙醇为溶剂, 单甲氧基聚乙二醇琥珀酰亚胺碳酸酯(mPEG-SC)为修饰剂, 对胰高血糖素样肽-1(GLP-1)进行了修饰反应条件的优化, 同时对单修饰产物Mono-PEG-GLP-1进行分离纯化, 并考察了其体外稳定性和体内活性.得到的优化反应条件为: GLP-1浓度1 mg/mL, mPEG-SC与GLP-1摩尔比1:1, 37℃下反应24 h, 该产物最高转化率达 77%.采用冷冻离心方式对Mono-PEG-GLP-1进行初步分离和浓缩, 然后经反相液相色谱进一步高效纯化, 纯度可达 97%以上.体外实验表明, Mono-PEG-GLP-1在血清中具有更好的稳定性及更强的抗胰蛋白酶消化能力.体内动物实验表明, Mono-PEG-GLP-1具有更好的降血糖作用. |
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其他语种文摘
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Glucagon-like peptide-1(GLP-1)was modified with monomethoxy polye(ethylene glycol succinimidyl carbonate)by using ethanol as a reaction medium. The reaction conditions were investigated and optimized, and the separation procedures of product Mono-PEG-GLP-1 were developed. After that, the stability in vitro and activity in vivo of Mono-PEG-GLP-1 were investigated. The optimized reaction conditions were obtained as follows:concentration of GLP-1 1.0 mg/mL, molar ratio of PEG to GLP-1 1:1, and reaction time 24 h at 37℃.Under the optimized conditions, the yield of Mono-PEG-GLP-1 was up to 77%.The Mono-PEG-GLP-1 was separated from reaction mixture by a preliminary centrifugation under frozen temperature and successive purification by reverse phase chromatography. The purity of Mono-PEG-GLP-1 was higher than 97%, as characterized by size exclusion chromatography. The Mono-PEG-GLP-1 showed better stability in plasma, decreased proteolysis to trypsin and better activity in vivo. |
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来源
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过程工程学报
,2010,10(3):593-597 【核心库】
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关键词
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胰高血糖素样肽-1
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单甲氧基聚乙二醇琥珀酰亚胺碳酸酯
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聚乙二醇修饰
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乙醇
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地址
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1.
中国科学院研究生院, 生化工程国家重点实验室, 北京, 100049
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中国科学院过程工程研究所, 生化工程国家重点实验室, 北京, 100190
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语种
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中文 |
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文献类型
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研究性论文 |
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ISSN
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1009-606X |
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学科
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生物化学;药学 |
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基金
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国家自然科学基金资助项目
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国家863计划
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北京市自然科学基金
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文献收藏号
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CSCD:3912443
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参考文献 共
14
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