MECHANISM-BASED INACTIVATION OF BACTERIAL AMINOGLYCOSIDE 3'-PHOSPHOTRANSFERASES

被引:47
作者
ROESTAMADJI, J [1 ]
GRAPSAS, I [1 ]
MOBASHERY, S [1 ]
机构
[1] WAYNE STATE UNIV,DEPT CHEM,DETROIT,MI 48202
关键词
D O I
10.1021/ja00106a009
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The design, synthesis, and properties of the first mechanism-based inactivators for bacterial aminoglycoside 3'-phosphotransferases [APH(3')s], enzymes which mediate resistance to kanamycins and related aminoglycoside antibiotics, are described. These molecules, whose design was based on the structures of aminoglycosides neamine and kanamycin B, serve as substrates for APH(3')s. However, as a deviation from the turnover process subsequent to phosphorylation, enzyme inactivation ensues. A mechanism is proposed for the inactivation chemistry. The general chemical principles described for the inactivation strategy herein hold the promise for the development of novel mechanism-based inactivators for other ''transferases'', such as protein kinases, acetyltransferases, nucleotidyltransferases, sulfotransferases, and the like.
引用
收藏
页码:80 / 84
页数:5
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