Thiasugars as Potential Glycosidase Inhibitor
Thiasugars as Potential Glycosidase Inhibitor
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硫代糖作为潜在的糖苷酶抑制剂
DOI：
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
H. Hashimoto
中科院分区：
文献类型：
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作者：
H. Yuasa;M. Izumi;H. Hashimoto
在我们研究的基础上，从活性和专一性两个方面讨论了碳水化合物的环硫类似物--人工合成硫糖作为糖苷酶抑制剂的潜力。本文还概述了这些类似物的合成方法，包括二糖和三糖衍生物。5-硫代果糖是第一个相对于糖苷酶显示KI值在微摩尔范围内的硫代吡喃。构效关系研究表明，其对岩藻糖苷酶的抑制作用部分归因于环硫与酶之间的疏水相互作用。具有硫代呋喃结构的磺胺化合物被创建为葡萄糖苷酶的过渡态模拟抑制剂，并且被发现具有弱的活性。后来，另一组人在天然产物沙拉辛醇中发现了相同的硫呋喃结构，沙拉辛醇是一种硫衍生物，是一种强烈的葡萄糖苷酶抑制剂。与合成的沙拉辛醇类似物的构效关系研究表明，硫离子及其内部反阴离子硫酸盐对抑制活性具有重要作用。
The potential of synthetic thiasugars, the ring sulfur analogs of carbohydrate, as glycosidase inhibitor was discussed in terms of activity and specificity, based on our own studies. The syntheses of these analogs including di- and tri-saccharide derivatives were also outlined. 5-Thiofucose was the first thiapyran to show a Ki value of micromolar range against a glycosidase. The structure-activity relationship studies indicated that its fucosidase inhibition was due in part to a hydrophobic interaction between the ring sulfur and the enzyme. A sulfylimine compound having a thiafuran structure was created as a transition-state analog inhibitor of glucosidases and found to have a weak activity. The same thiafuran structure was later found by another group in a natural product, salacinol, which is a sulfonium derivative and is a strong glucosidase inhibitor. The structure-activity relationship study with synthetic analogs of salacinol indicated importance of the sulfonium ion and its internal counter anion, sulfate, for the inhibition activity.