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化学进展 2014, Vol. 26 Issue (09): 1527-1536 DOI: 10.7536/PC140313 前一篇   后一篇

所属专题： 酶化学

• 综述与评论 •

环肽类组蛋白去乙酰化酶抑制剂

李晓晖*, 黄美玲, 刘丽娜, 王燕云   

  1. 大连理工大学生命科学与技术学院 大连 116024
  • 收稿日期:2014-03-01 修回日期:2014-05-01 出版日期:2014-09-15 发布日期:2014-07-09
  • 通讯作者: 李晓晖 E-mail:lxhxh@dlut.edu.cn
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Cyclopeptide Histone Deacetylase Inhibitors

Li Xiaohui*, Huang Meiling, Liu Lina, Wang Yanyun   

  1. School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China
  • Received:2014-03-01 Revised:2014-05-01 Online:2014-09-15 Published:2014-07-09

组蛋白去乙酰化酶抑制剂是一类以组蛋白去乙酰化酶为靶点的新型靶向抗肿瘤药物，在抗增殖、促凋亡、促分化、阻滞细胞生长周期、抗血管生成等方面有很好的作用。组蛋白去乙酰化酶抑制剂以其独特的抗肿瘤作用机理，在研发肿瘤治疗药物中占有重要地位。在组蛋白去乙酰化酶抑制剂分类中，环肽类抑制剂结构最为复杂，对多种类型的实体瘤及血液学癌细胞均具有良好的对抗作用。本文针对天然和化学合成的环肽类组蛋白去乙酰化酶抑制剂中金属结合区、表面识别区以及连接区的结构特点进行了综述，并描述了各类抑制剂对酶的抑制活性和抗肿瘤增殖活性。对抑制剂不同结构区的修饰、改造可以使抑制剂对不同肿瘤细胞具有高效性和特异性作用，通过构效关系研究寻找具有高效低毒、靶向性环肽类抑制剂的结构规律，可为研究开发抗肿瘤药物提供帮助。

关键词： 组蛋白去乙酰化酶, 组蛋白去乙酰化酶抑制剂, 环肽, 抗肿瘤

Histone deacetylase inhibitor is a novel class of histone deacetylase targeted anti-cancer drug, which takes excellent effects on anti-proliferation, pro-apoptosis, pro-differentiation, cell cycle arrest, anti-angiogenesis and so on. Histone deacetylase inhibitor plays an important role in the development of anticancer drug with its unique anti-tumor mechanism. Among the histone deacetylase inhibitors, the cyclopeptide histone deacetylase inhibitor with the most complicated structure has good antagonism on various types of solid tumors and hematologic cancer. In this review, the structural features of the metal binding region, the surface recognition region and the linker region of natural and synthetic cyclic peptide histone deacetylase inhibitors are summarized, and the inhibitory activity and anti-tumor proliferative activity of various inhibitors are described. Modification of different structure domains can make inhibitors with high efficiency and specificity on different tumor cells. We expect to find the structure rule of the high efficient and low toxic targeted peptide inhibitors through structure-activity relationships, providing new sights for investigation of anti-cancer drugs.

Contents
1 Introduction
2 Histone deacetylase inhibitors and classification
3 Cyclopeptide histone deacetylase inhibitors
3.1 Cyclopeptide histone deacetylase inhibitors containing ketone
3.2 Cyclopeptide histone deacetylase inhibitors containing hydroxamic acid
3.3 Cyclopeptide histone deacetylase inhibitors containing sulfur
3.4 Cyclopeptide histone deacetylase inhibitors containing carboxylic acid or amide
3.5 Other histone deacetylase inhibitors
4 Conclusion

Key words: histone deacetylase, histone deacetylase inhibitor, cyclic peptides, anti-tumor

中图分类号: 

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摘要

环肽类组蛋白去乙酰化酶抑制剂