高等学校化学学报

高等学校化学学报

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Exendin-4类似物的生物活性及结构

宋相伟1, 王雪丽2, 熊新辉1, 牛建丽1, 王仕擎3, 王丽萍1, 李惟1   

    1. 吉林大学生命科学学院生物大分子实验室,
    2. 分子酶学工程教育部重点实验室, 长春 130021;
    3. 吉林大学生物与农业工程学院, 长春130022
  • 收稿日期:2007-12-06 修回日期:1900-01-01 出版日期:2008-06-10 发布日期:2008-06-10
  • 通讯作者: 王丽萍

Bioactivity and Structure of Analogues of Exendin-4

SONG Xiang-Wei1, WANG Xue-Li2, XIONG Xin-Hui1, NIU Jian-Li1 , WANG Shi-Qing3, WANG Li-Ping1*, LI Wei1   

    1. College of Life Science, Jilin University,
    2. Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130021, China;
    3. School of Biological and Agricultural Engineering, Jilin University, Changchun 130022, China
  • Received:2007-12-06 Revised:1900-01-01 Online:2008-06-10 Published:2008-06-10
  • Contact: WANG Li-Ping

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被引次数

12

摘要： 针对Exendin-4的N端螺旋中第10~18位氨基酸序列LSKQMEEEA设计了Ex1, Ex2序列, 并进行活性、稳定性及其结构方面的研究, 为进一步设计具有Exendin-4活性的短肽抗酶解序列提供了理论依据, 进而为开发可供口服的类肽糖尿病药物奠定了结构理论基础.

关键词: Exendin-4类似物, 螺旋结构, 稳定性, 生物活性

Abstract: Exendin-4 is an incretin mimetic that has been studied as a potent drug for the treatment of the type 2 diabetes. To screen the shorter analogues of Exendin-4 that have the same bioactivity, we designed two analogues of Exendin-4: Ex1, deleting this sequence and Ex2, replacing this sequence with three Alas. The proliferation assay of RINm-5F cell using MTT suggested the bioactivity of Ex1 and Ex2 was lower compared to that of Exendin-4 caused by the deletion of LSKQMEEEA. Ex1 and Ex2 had the same strong stability against DPPⅣ with Exendin-4. CD data suggested the helix content of Ex1 had a significant lost, but the helix content of Ex2 was the same as that of Exendin-4. The emission maximum of Ex1 was red-shifted of 3 nm relative to Exendin-4, the absence of this sequence made Trp25 more apt to hydrophilic and the Trp-cage became looser. So we have designed Ex2, the mimetic of Exendin-4 that had the same bioactivity and strong stability against DPPⅣ with Exendin-4 successfully. It became a solid foundation for designing shorter analogues of Exendin-4 for oral drug of diabetes.

Key words: Exendin-4 analogue, Helix structure, Stability, Bioactivity

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