Probing the conformational changes int he enzymatic hydrolysis of 2-acetamido-2-deoxy-β-D-glucopyranosides

被引：14

作者：

Böhm, M ^{[1
]}

Vasella, A ^{[1
]}

机构：

[1] ETH Honggerberg, Organ Chem Lab, CH-8093 Zurich, Switzerland

来源：

HELVETICA CHIMICA ACTA | 2004年 / 87卷 / 10期

关键词：

D O I：

10.1002/hlca.200490229

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The isoquinuclidines 7 and 8 were synthesised and tested as inhibitors of hexosaminidases from jack beans and from bovine kidney. These isoquinuclidines mimick the B-1,B-4-conformer of a N-acetyl-glucosamine-derived beta-D-glucopyranoside; they are competitive inhibitors with K-i values from 0.014 to 0.30 muM. The strong inhibition of these enzymes agrees with the hypothesis that the enzymatic hydrolysis of 2-acetamido-2-deoxy-beta-D-glucopyranosides proceeds via a boat-like conformer with a pseudo-axial scissile glycosidic bond and a pseudo-axial acetamido substituent optimally oriented to effect an intramolecular substitution of the aglycon.

引用

页码：2566 / 2573

页数：8

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