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化学进展 2016, Vol. 28 Issue (11): 1712-1720 DOI: 10.7536/PC160442 前一篇   

所属专题： 酶化学

• 综述与评论 •

唾液酸转移酶抑制剂的设计与发现

郭键1,2, 贺耘1*, 叶新山2*   

  1. 1. 重庆大学药学院 创新药物研究中心 重庆 401331;
    2. 北京大学医学部天然药物及仿生药物国家重点实验室 北京 100191
  • 收稿日期:2016-04-01 修回日期:2016-06-01 出版日期:2016-11-15 发布日期:2016-10-09
  • 通讯作者: 贺耘, 叶新山 E-mail:yun.he@cqu.edu.cn;xinshan@bjmu.edu.cn
  • 基金资助:
    国家自然科学基金项目（No.21072014）资助
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Design and Discovery of Sialyltransferase Inhibitors

Guo Jian1,2, He Yun1*, Ye Xin-Shan2*   

  1. 1. School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chonqing University, Chongqing 401331, China;
    2. State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China
  • Received:2016-04-01 Revised:2016-06-01 Online:2016-11-15 Published:2016-10-09
  • Supported by:
    The work was supported by the National Natural Science Foundation of China (No. 21072014).
糖缀合物末端的唾液酸化修饰参与了很多重要的生理及病理过程，尤其是肿瘤细胞表面唾液酸过度表达，能够通过多种途径和机制促进肿瘤转移。唾液酸转移酶是人体内负责唾液酸化修饰的合成酶，良好的唾液酸转移酶抑制剂不仅能够充当糖生物学研究的探针分子，而且有望成为临床治疗中亟需的抑制肿瘤转移的药物。本文综述了近年来唾液酸转移酶抑制剂设计及发现的研究进展，重点介绍了不同类型抑制剂的设计思路及构效关系。此外，对该研究领域当前面临的一些挑战进行了探讨，并对其发展趋势进行了展望。
关键词： 唾液酸转移酶, 抑制剂, 构效关系, 模拟物
Sialylation at the non-reducing end of glycoconjugates is involved in lots of important physiological and pathological processes. Especially cancer cells express high density of sialic acids known as hypersialylation that contributes to cancer cell progression and metastasis. Sialyltransferase is the glycosyltransferase in charge of sialylation of glycoconjugates. Effective sialyltransferase inhibitors could be not only of medicinal interests, especially in the therapy of cancer diseases, but also biological probes for studying fuctions of sialylation in glycobiology. Here we review recent progress of design and discovery of sialyltransferase inhibitors. The major content is about the design of different types of inhibitors and their structure-activity relationship. The current challenges and development trends are also proposed.

Contents
1 Introduction
2 Relationship between sialic acids and cancers
3 Design and discovery of sialyltransferase inhibitors
3.1 Donor-analog inhibitors
3.2 Acceptor-analog inhibitors
3.3 Bisubstrate-analog inhibitors
3.4 Transition-state-analog of the sialyl donor inhibitors
3.5 Other types of inhibitors
4 Conclusion

Key words: sialyltransferase, inhibitors, structure-activity relationship, mimics

中图分类号: 

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