高等学校化学学报 ›› 2015, Vol. 36 ›› Issue (7): 1310-1314.doi: 10.7503/cjcu20150087

• 有机化学 • 上一篇    下一篇

酚化合物对胰岛素淀粉样纤维化的抑制作用

张玉洁, 曹娜, 曾成鸣()   

  1. 陕西师范大学化学与化工学院, 西安 710119
  • 收稿日期:2015-01-26 出版日期:2015-07-10 发布日期:2015-06-03
  • 作者简介:联系人简介: 曾成鸣, 男, 博士, 教授, 博士生导师, 主要从事蛋白质化学方面的研究. E-mail:chengmingzeng@snnu.edu.cn
  • 基金资助:
    中央高校基础研究基金(批准号: GK20133001)资助

Inhibitory Effect of Phenolic Compounds on Amyloid Fibrillation of Insulin

ZHANG Yujie, CAO Na, ZENG Chengming*()   

  1. School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710119, China
  • Received:2015-01-26 Online:2015-07-10 Published:2015-06-03
  • Contact: ZENG Chengming E-mail:chengmingzeng@snnu.edu.cn

摘要:

采用牛胰岛素作为模型多肽分子, 对几种结构相近的简单多酚的抗多肽淀粉样纤维化作用进行了研究. 结果表明, 邻苯二酚和对苯二酚对胰岛素纤维化具有抑制作用, 并通过形成醌中间体对多肽链进行修饰, 与对苯醌作用类似; 而苯酚和间二苯酚在相同条件下, 既不能修饰多肽也无抑制纤维化作用. 在无氧条件下, 邻苯二酚和对苯二酚对胰岛素纤维化的抑制作用明显降低, 说明酚化合物经氧化形成的醌中间体是其抗胰岛素纤维化的主要活性结构.

关键词: 酚化合物, 胰岛素, 淀粉样纤维化, 醌, 醌修饰肽

Abstract:

More than 20 human diseases are considered to be associated with amyloid fibrillation in polypeptides. Polyphenolic compounds have been demonstrated to disrupt amyloid structures and attenuate cytotoxicity of amyloid fibrils. In the present study, the inhibitory effects of four phenolic compounds on amyloid formation were investigated using bovine insulin as a model peptide. The results indicated that catechol and hydroquinone inhibited insulin fibrillation and bonded to the peptide chains with quinone moieties, showing a similar effect to benzoquinone. In contrast, phenol and resorcinol did not modify insulin with a quinone moiety, showing no effect on amyloid fibrillation. Furthermore, catechol and hydroquinone were less effective as an inhibitor of insulin fibrillation under anaerobic conditions, suggested that the formation of quinone intermediates via oxidation and subsequently transform insulin into quinopeptide were prerequisites for a phenolic compound to inhibit amyloid fibrillation. The results show that quinone intermediates are the active form for phenolic compounds to inhibit insulin amyloid fibrillation.

Key words: Phenolic compound, Insulin, Amyloid fibrillation, Quinone, Quinopeptide

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