Towards the development of novel antibiotics: Synthesis and evaluation of a mechanism-based inhibitor of Kdo8P synthase

被引：56

作者：

Du, SC

Faiger, H

Belakhov, V

Baasov, T ^{[1
]}

机构：

[1] Technion Israel Inst Technol, Dept Chem, IL-32000 Haifa, Israel

[2] Technion Israel Inst Technol, Inst Catalysis Sci & Technol, IL-32000 Haifa, Israel

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 1999年 / 7卷 / 12期

关键词：

Kdo8P synthase; lipopolysaccharide; mechanism-based inhibitors;

D O I：

10.1016/S0968-0896(99)00233-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The design and two synthetic pathways to aminophosphonate 4 which mimics the ionic and steric properties of putative oxocarbenium intermediate 3 in the Kdo8P synthase-catalyzed reaction are reported. It was found that 4 is a slow-binding, most potent inhibitor of the enzyme yet tested, with a K-i value of 0.4 mu M. (C) 1999 Elsevier Science Ltd. All rights reserved.

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页码：2671 / 2682

页数：12

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