截短胰高血糖素样肽-1的构象研究

高等学校化学学报 ›› 2010, Vol. 31 ›› Issue (7): 1337.

截短胰高血糖素样肽-1的构象研究

聂新华¹, 张涛¹, 李元², 郑学仿¹, 曹洪玉¹, 唐乾¹

1. 大连大学生物工程学院, 大连116622;
2. 大连帝恩生物工程有限公司, 大连 116600

收稿日期:2009-12-08 出版日期:2010-07-10 发布日期:2010-07-10
通讯作者: 李元, 男, 博士, 教授, 主要从事免疫学研究. E-mail: dalianliyuan@yaoo.com.cn；郑学仿, 男, 博士, 教授, 主要从事生物无机化学研究. E-mail: dlxfzheng@163.com
基金资助:
国家“十一五”计划科技重大专项“重大医药创制”项目(批准号: 2009zx09102-53)、辽宁省高校创新团队项目(批准号: 2006T002, 2008T005, 2009T003)和大连市科技计划项目(批准号: 2008E11SF170)资助.

Conformation Research of Shorted Glucagon-like Peptide-1

NIE Xin-Hua¹, ZHANG Tao¹, LI Yuan^2*, ZHENG Xue-Fang^1*, CAO Hong-Yu¹, TANG Qian¹

1. College of Bioengineering, Dalian University, Dalian 116622, China;
2. Dalian DN Bio-engineering Co., Ltd., Dalian 116600, China

Received:2009-12-08 Online:2010-07-10 Published:2010-07-10
Contact: LI Yuan. E-mail: dalianliyuan@yaoo.com.cn；ZHENG Xue-Fang. E-mail: dlxfzheng@163.com
Supported by:
国家“十一五”计划科技重大专项“重大医药创制”项目(批准号: 2009zx09102-53)、辽宁省高校创新团队项目(批准号: 2006T002, 2008T005, 2009T003)和大连市科技计划项目(批准号: 2008E11SF170)资助.

摘要/Abstract

摘要：

截短胰高血糖素样肽-1(sGLP-1)不仅具备刺激胰岛β细胞增生和降低血糖的功能, 而且半衰期较长, 具有非常好的新药开发前景. 为了阐明sGLP-1的功能, 本文运用圆二色光谱和荧光光谱探究了sGLP-1在不同条件下的构象, 结果表明, sGLP-1在磷酸盐缓冲液中主要呈无规则构象, 螺旋含量很低; 在含十二烷基硫酸钠或三氟乙醇的磷酸盐缓冲液中主要呈螺旋构象. 溶液pH值和温度变化对sGLP-1的构象影响显著. sGLP-1保留了结合并激活受体的关键残基, 在受体的诱导下, 在体内形成正确构象, 从而结合并激活受体, 发挥它的功能. 研究结果表明, 适当缩短GLP-1 C端片段, 能获得作用时间长、效力高的GLP-1类似物.

关键词: 截短胰高血糖素样肽-1; 圆二色光谱; 荧光光谱; 构象

Abstract:

Shorted glucagon-like peptide-1(sGLP-1) not only stimulate proliferation of pancreatic beta cells and decrease blood glucose, but also has a longer half-life. This make sGLP-1 has become a potential new drug in the future. In order to elucidate the function of sGLP-1, this study investigates the conformation of sGLP-1 in different conditions by circular dichroism spectrum and fluorescence spectrum. The conformations of sGLP-1 in phosphate buffer are mostly unordered structure and very low helix, and are mostly α-helix in phosphate buffer containing SDS or TFE. Temperature and pH values of solutions have great influences on the conformation of sGLP-1. sGLP-1 preserve the critical residues which are responsible for binding and activating receptor, Induced by receptor, sGLP-1 can form the correct conformation which can bind and activate receptor in vivo, then realize its function. The results show that appropriately truncate C-terminal segment of GLP-1, may obtain long-term and high efficiency GLP-1 analogues.

Key words: Shorted glucagon-like peptide-1; Circular dichroism spectrum; Fluorescence spectrum; Conformation

TrendMD:

聂新华, 张涛, 李元, 郑学仿, 曹洪玉, 唐乾. 截短胰高血糖素样肽-1的构象研究. 高等学校化学学报, 2010, 31(7): 1337.

NIE Xin-Hua, ZHANG Tao, LI Yuan*, ZHENG Xue-Fang*, CAO Hong-Yu, TANG Qian. Conformation Research of Shorted Glucagon-like Peptide-1. Chem. J. Chinese Universities, 2010, 31(7): 1337.

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