胰高血糖素样肽-1(7-36)酰胺的微波辅助固相合成、聚乙二醇化及生物活性研究
Microwave-assisted solid phase synthesis, PEGylation, and biological activity studies of glucagon-like peptide-1(7-36) amide.
作者信息
Chi Yushi, Zhang Huibin, Huang Wenlong, Zhou Jinpei, Zhou Yinghong, Qian Hai, Ni Shuaijian
机构信息
Center of Drug Research, China Pharmaceutical University, Nanjing 210009, China.
出版信息
Bioorg Med Chem. 2008 Aug 15;16(16):7607-14. doi: 10.1016/j.bmc.2008.07.019. Epub 2008 Jul 12.
The insulinotropic hormone glucagon-like peptide-1 (GLP-1) is rapidly inactivated in the body. In order to improve its stability, we replaced the enzymatic hydrolyzation position Ala(8)with Gly and replaced Ala(30) with Cys firstly. Then the modified peptide was further PEGylated at thiol group of Cys(30). Biological activity studies showed that the resulting mPEG-MAL-Gly(8)-Cys(30)-GLP-1(7-36)-NH(2) exhibited long-lasting effect while maintaining moderate glucose-lowering activity.
促胰岛素激素胰高血糖素样肽-1（GLP-1）在体内会迅速失活。为了提高其稳定性，我们首先将酶解位点的丙氨酸（Ala）(8)替换为甘氨酸（Gly），并将丙氨酸（Ala）(30)替换为半胱氨酸（Cys）。然后，对修饰后的肽在半胱氨酸（Cys）(30)的巯基处进一步进行聚乙二醇化修饰。生物活性研究表明，所得的甲氧基聚乙二醇马来酰亚胺-甘氨酸（8）-半胱氨酸（30）-GLP-1（7-36）-NH2具有长效作用，同时保持适度的降血糖活性。
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