中文摘要：

用单甲氧基聚乙二醇-丙醛（mPEG-ALD）、单甲氧基聚乙二醇-丁醛（mPEG-ButyrALD）和单甲氧基聚乙二醇-琥珀酰亚胺碳酸酯（mPEG-SC）对猪胰岛素进行化学修饰.考察了反应时间、pH、物质的量比及分子量等因素对修饰效果的影响.通过HPLC,MALDI-TOF-MS（基质辅助激光解吸时间飞行质谱）,SDS-PAGE（十二烷基硫酸钠-聚丙烯酰胺凝胶电泳）和TNBS（三硝基苯磺酸钠法）等表征发现mPEG-ButyrALD具有更高的修饰选择性和修饰率.圆二色光谱（CD）分析修饰产物的二级结构发现,胰岛素经mPEG衍生物修饰后,二级结构基本没有改变.动物实验表明,mPEG-ButyrALD修饰胰岛素后半衰期延长,因而可以延长降血糖作用时间,改善胰岛素药效.

英文摘要：

Pork insulin was modified by three kinds of mPEG derivatives（mPEG-ALD,mPEG-ButyrALD and mPEG-SC） with different active moieties.The effects of reaction time,pH,molar ratio and molecular weight on the modification rate and site-selectivity were investigated.The results showed that mPEG-ButyrALD-INS had higher site-selectivity and modification rate compared to the other two modifiers characterized by HPLC,matrix-assisted laser desorption/ionization time-of-flight mass spectrometry（MALDI-TOF-MS）,sodium dodecyl sulfate polyacrylamide gel electrophoresis（SDS-PAGE） and trinitrobenzene sulfonic acid（TNBS）.The secondary structure of the mPEGylated insulins was studied by circular dichroism（CD）.It is found that the secondary structure of insulin was changed hardly after mPEGylation.The in vivo experiment results showed that mPEG-ButyrALD-INS displayed longer half-life and extended action profiles.