Cyclic amidine sugars as transition-state analogue inhibitors of glycosidases: Potent competitive inhibitors of mannosidases
Cyclic amidine sugars as transition-state analogue inhibitors of glycosidases: Potent competitive inhibitors of mannosidases
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DOI：
10.1021/ja037822r
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发表时间：
2004-02-25
影响因子：
15
通讯作者：
Mioskowski, C
中科院分区：
文献类型：
--
作者：
Heck, MP;Vincent, SP;Mioskowski, C
合成了一系列带有不同环外胺、醇或烷基官能团的单环糖脒以及源自 D-葡萄糖和 D-甘露糖的双环脒，并测试它们作为各种糖苷酶的抑制剂。所有制备的化合物均表现出对糖苷酶良好至优异的抑制作用。特别是，带有环外乙胺部分的双阳离子 D-甘露脒 9b 被证明是 α- 和 β- 甘露糖苷酶的选择性竞争性抑制剂 (K-i = 6 nM)，使其成为迄今为止报道的这些糖苷酶最有效的抑制剂。有利的 B-2、B-5 船构象可能解释了与其他糖苷酶相比，甘露糖苷酶抑制的选择性。
A series of monocyclic glycoamidines bearing different exocyclic amine, alcohol, or alkyl functionalities and bicyclic amidines derived from D-glucose and D-mannose were synthesized and tested as inhibitors of various glycosidases. All the prepared compounds demonstrated good to excellent inhibition toward glycosidases. In particular, the biscationic D-mannoamidine 9b bearing an exocyclic ethylamine moiety proved to be a selective competitive inhibitor of alpha- and beta-mannosidases (K-i = 6 nM) making it the most potent inhibitor of these glycosiclases reported to date. A favorable B-2,B-5 boat conformation might explain the selectivity of mannosidase inhibition compared to other glycosiclases.