Inhibitors of UDP-galactopyranose mutase thwart mycobacterial growth

被引：86

作者：

Dykhuizen, Emily C. ^{[1
]}

May, John F. ^{[2
]}

Tongpenyai, Aimon ^{[1
]}

Kiessling, Laura L. ^{[1
,2
]}

机构：

[1] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA

[2] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2008年 / 130卷 / 21期

关键词：

D O I：

10.1021/ja8018687

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Galactofuranose (Galf) residues are fundamental components of the cell wall of mycobacteria. A key enzyme, UDP-galactopyranose mutase (UGM), that participates in Galf incorporation mediates isomerization of UDP-Galf from UDP-galactopyranose (UDP-Galp). UGM is of special interest as a therapeutic target because the gene encoding it is essential for mycobacterial viability and there is no comparable enzyme in humans. We used structure-activity relationships and molecular design to devise UGM inhibitors. From a focused library of synthetic aminothiazoles, several compounds that block the UGM from Klebsiella pneumoniae or Mycobacterium tuberculosis were identified. These inhibitors block the growth of M. smegmatis.

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页码：6706 / +

页数：3

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