吉林大学学报(理学版) ›› 2021, Vol. 59 ›› Issue (4): 988-992.

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Exendin-4螺旋结构对生物活性及稳定性的影响

宋相伟1 ,   窦馨月1,  沙悦1,  罗锐1, 王雪丽2   

  1. 1.长春师范大学 生命科学学院, 长春130032; 2.吉林工商学院 粮食学院, 长春130507
  • 收稿日期:2020-12-02 出版日期:2021-07-26 发布日期:2021-07-26
  • 通讯作者: 王雪丽 E-mail:wangxueli@jlbtc.edu.cn

Effect of  Helical Structure on Bioactivity and Stability of Exendin-4

SONG Xiangwei1 , DOU Xinyue1,   SHA Yue1,  LUO Rui1,  WANG Xueli2   

  1. 1. Life Science of College, Changchun Normal University,  Changchun 130032,  China;
    2. Grain College, Jilin Business and Technology College, Changchun 130507,  China
  • Received:2020-12-02 Online:2021-07-26 Published:2021-07-26

摘要: 针对Exendin-4的螺旋结构特点, 采用去掉螺旋序列、 用3个连续Ala替换螺旋以及Gln13替换为Tyr13的方式对N端α-螺旋及C端α-螺旋进行改造, 设计出4个结构模拟物. 通过圆二光谱和荧光光谱进行结构分析, 结合模拟物生物活性实验, 分析Exendin-4螺旋结构与生物活性的关系. 结果表明:  Exendin-4的N端螺旋比C端螺旋对生物活性影响更大; 在抗二肽基肽酶(DPPⅣ酶)的稳定性实验中, C端螺旋比N端螺旋具有更好维系Exendin-4稳定性的作用; 螺旋结构中Tyr13可作为提高Exendin-4生物活性的重要优化位点.

关键词: Exendin-4; , 螺旋; , 生物活性; , 稳定性

Abstract: Based on the helical character of Exendin-4,  we modified the N terminal α-helix and C terminal α-helix by deleting helix,  replacing the helix with 3 Alas and changing Gln13 with Tyr13, and  designed 4 structral mimetics. Combined with the bioactivity experiment of the mimetics, we analyzed the relationship between the helical structure and bioactivity of Exendin-4 by  circular dichroism analysis and fluorescent spectroscopy analysis. The results show that N terminal α-helix is more important than C terminal α-helix to promote the bioactivity of Exendin-4;  C terminal α-helix is more effective than N terminal α-helix to maitain the stability of Exendin-4 to DPPⅣ;  Tyr13 in the helical structure can be used as an important optimized site to improve the bioactivity of Exendin-4.

Key words: Exendin-4; , helix; bioactivity; , stability

中图分类号: 

  • Q518.1