Multivalent Effect in Glycosidase Inhibition: The End of the Beginning
Multivalent Effect in Glycosidase Inhibition: The End of the Beginning
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DOI：
10.1002/tcr.201900004
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发表时间：
2020-01-01
期刊：
影响因子：
6.6
通讯作者：
Compain, Philippe
中科院分区：
文献类型：
--
作者：
Compain, Philippe
糖苷酶是一种普遍存在的酶，参与多种关键的生物过程，如能量吸收或细胞壁降解。因此，特异性糖苷酶抑制剂的设计一直是学术界和制药工业中密集研究努力的主题。然而，直到最近，多价对糖苷酶抑制作用的影响的研究几乎完全被忽视。以下帐户将回顾我们的研究小组内的多价糖模拟物设计的十年旅程，从糖苷酶抑制的第一个强多价效应的发现到杰克豆α-甘露糖苷酶与多聚体抑制剂复合的高分辨率晶体结构，显示迄今为止报道的最大结合增强。
Glycosidases are ubiquitous enzymes involved in a diversity of key biological processes such as energy uptake or cell wall degradation. The design of specific glycosidase inhibitors has been therefore the subject of intense research efforts in academia and pharmaceutical industry. However, until recently, the study of the impact of multivalency on glycosidase inhibition was almost completely neglected. The following account will review our ten year journey on the design of multivalent glycomimetics within our research group, from the discovery of the first strong multivalent effect in glycosidase inhibition to the high-resolution crystal structures of Jack bean alpha-mannosidase in complex with the multimeric inhibitor displaying the largest binding enhancements reported so far.