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有机化学
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有机化学 ›› 2008, Vol. 28 ›› Issue (11): 1932-1936. 上一篇    下一篇

研究论文

胰高血糖素样肽-1类似物的合成及其生物学活性研究

迟玉石; 黄文龙*; 张惠斌*; 周金培; 周映红; 倪帅健; 钱 海
  

  1. (中国药科大学新药研究中心 南京 210009)
  • 收稿日期:2008-03-12 修回日期:2008-04-15 发布日期:2008-11-18
  • 通讯作者: 黄文龙

Synthesis and Biological Activity Studies of Glucagon-Like Peptide-1 Analogues

CHI, Yu-Shi ; HUANG, Wen-Long*; ZHANG, Hui-Bin* ; ZHOU, Jin-Pei ; ZHOU, Ying-Hong ; NI, Shuai-Jian ; Qian, Hai
  

  1. (Center of Drug Research, China Pharmaceutical University, Nanjing 210009)
  • Received:2008-03-12 Revised:2008-04-15 Published:2008-11-18
  • Contact: HUANG, Wen-Long

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1497

被引次数

7 | 2

通过改变胰高血糖素样肽-1 (GLP-1)易被酶水解部位, 采用Fmoc/t-Bu正交保护固相合成策略, 并运用微波照射促进高效快速地合成了抗二肽基肽酶IV (DPP IV)的GLP-1类似物, 最后经过反相制备高效液相系统纯化得到目标多肽纯品. 生物学活性研究结果显示, 改造后的GLP-1类似物能有效抵抗DPP IV的水解, 并且有很好的降血糖活性. 所合成的GLP-1及其类似物的分子量和纯度均经过电喷雾质谱和高效液相确证.

关键词: 二肽基肽酶IV, 固相合成, 微波, 胰高血糖素样肽-1

Glucagon-like Peptide-1 (GLP-1) analogues were designed through the modification of the enzymatic hydrolyzation position. The synthesis of GLP-1 analogues was implemented rapidly and efficiently under microwave irradiation, using Fmoc/t-Bu orthogonal protection solid phase strategy. The crude peptides were purified by preparative RP-HPLC. The results of biological activity research showed that the GLP-1 analogues had great resistance to the degradation by dipeptidyl peptidase (DPP IV) and decreased the blood glucose prominently. The molecular weight and purity of the GLP-1 analogues have been confirmed through the electrospray mass spectrometry analysis and the HPLC analysis.

Key words: DPP IV, solid phase synthesis, microwave, GLP-1