唾液酸转移酶抑制剂的设计与发现

郭键; 贺耘; 叶新山

doi:10.7536/PC160442

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

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唾液酸转移酶抑制剂的设计与发现

^1,2

^1*

^2*

作者信息 +

Design and Discovery of Sialyltransferase Inhibitors

Guo Jian^1,2, He Yun^1*, Ye Xin-Shan^2*

Author information +

文章历史 +

摘要

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。

Abstract

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

Graphical abstract

关键词

唾液酸转移酶 / 抑制剂 / 构效关系 / 模拟物

Key words

sialyltransferase / inhibitors / structure-activity relationship / mimics

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郭键, 贺耘, 叶新山. 唾液酸转移酶抑制剂的设计与发现[J]. 化学进展, 2016, 28(11): 1712-1720 DOI:10.7536/PC160442

Guo Jian, He Yun, Ye Xin-Shan. Design and Discovery of Sialyltransferase Inhibitors[J]. Progress in Chemistry, 2016, 28(11): 1712-1720 DOI:10.7536/PC160442

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