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胰高血糖素样肽-1的聚乙二醇定点修饰

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Source
Institutional Repository of Institute of Process Engineering, CAS (IPE-IR)
Keywords
  • 胰高血糖素样肽-1
  • 聚乙二醇
  • 定点修饰
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Abstract

采用分子量为5kDa的单甲氧基聚乙二醇琥珀酰亚胺碳酸酯(mPEG-SC)修饰胰高血糖素样肽-1(GLP-1),建立了GLP-1的定点修饰反应及分离纯化工艺,考察了修饰反应各因素对单修饰产物得率及体外活性的影响,得到优化修饰条件为:pH7.5,50mmol/L Na2HPO4-NaH2PO4缓冲液,GLP-1浓度1mg/mL,PEG/GLP-1摩尔比2:1,4℃下反应1h.在此条件下,单修饰PEG-GLP-1得率达50%.反相高效液相色谱分离纯化所得单修饰产品纯度达98%,体外活性保留为未修饰GLP-1的86%,其在Sprague-Dawley远交群大鼠体内的循环半衰期为60min,比原肽提高了20倍.

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