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化学进展 2015, Vol. 27 Issue (9): 1260-1274 DOI: 10.7536/PC150203 前一篇   后一篇

• 综述与评论 •

模拟肽的构象限制在药物设计中的应用

侯辉, 孙德群*   

  1. 山东大学(威海)海洋学院 威海 264209
  • 收稿日期:2015-02-01 修回日期:2015-04-01 出版日期:2015-09-15 发布日期:2015-06-24
  • 通讯作者: 孙德群 E-mail:dequn.sun@sdu.edu.cn
下载PDF ( 1850 ) 引用
导出 被引次数 ( 2 | 1 )

Conformational Restriction of Peptidomimetics in Drug Design

Hou hui, Sun Dequn*   

  1. Marine College, Shandong University at Weihai, Weihai 264209, China
  • Received:2015-02-01 Revised:2015-04-01 Online:2015-09-15 Published:2015-06-24
构象限制的模拟肽具有更好的生物活性和代谢稳定性,可以作为酶和受体活性位点的多肽替代物,是重要的药物设计工具。将特定的结构引入到生物活性肽中进行构象限制就得到了模拟肽,设计合成特定结构的模拟肽,需要一些方法作为指导,这些方法可以使模拟肽按设想产生特定的生物活性而减少设计的盲目性。本文综述了模拟肽构象限制的两类方法,即模拟肽的局部构象限制和模拟肽的整体环化。通过这两种主要方式的结构改进得到的构象限制的模拟肽,对改进模拟肽的药效学和药代动力学性质起了重要作用,包括提高其生物活性、选择性、代谢的稳定性和吸收性质。
关键词： 药物设计, 模拟肽, 构象限制, 生物活性, 代谢稳定性
Peptidomimetics are important drug design tools as substitutes for peptides in active sites of enzymes and receptors. The incorporation of some specific structure into biologically active peptides may lead to conformationally restricted peptidomimetics. Conformational restriction of peptidomimetics may significantly improve the pharmacodynamic properties and pharmacokinetic properties, including bioactivity, selectivity to receptors, stability of metabolism and absorption properties. To develop new approaches, allow rational design and synthesis of restricted peptidomimetics is of importance. Herein, we review two approaches to access conformationally restricted peptidomimetics, the local conformational restriction approach and the overall cyclization approach.

Contents
1 Introduction
2 Local conformational restriction of peptide
2.1 Cα-methylated amino acids
2.2 N-methylated amino acids
2.3 Cα,Cα-dialkyl amino acids
2.4 Cβ,Cβ-dialkyl amino acids
2.5 α,β-unsaturated amino acids
2.6 C-C cyclization of amino acids
2.7 C-N cyclization of amino acids
2.8 N-N cyclization of amino acids
3 The overall cyclization of peptides
3.1 The overall cyclization methods of peptides
3.2 Other cyclization methods expect lactam bond
4 Conclusion

Key words: drug design, peptidomimetics, conformational restriction, bioactivity, metabolic stability

中图分类号: 

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