O-Aryloxycarbonyl Hydroxamates: New -Lactamase Inhibitors That Cross-Link the Active Site
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- 作者：Pauline N. Wyrembak ; Kerim Babaoglu ; Ryan B. Pelto ; Brian K. Shoichet ; R. F. Pratt
- 刊名：Journal of the American Chemical Society
- 出版年：2007
- 出版时间：August 8, 2007
- 年：2007
- 卷：129
- 期：31
- 页码：9548 - 9549
- 全文大小：115K
- 年卷期：v.129,no.31(August 8, 2007)
- ISSN：1520-5126
文摘
O-Aryloxycarbonyl hydroxamates represent a new class of 
-lactamase inhibitors. N-Benzyloxycarbonyl-O-(phenoxycarbonyl) hydroxylamine, for example, inactivates the class C Enterobacter cloacae P99 -lactamase with a rate constant of 6.1 × 103 s-1 M-1; approximately two turnover events accompany the inhibition. N-Benzyloxycarbonyl-O-[(3-carboxyphenoxy)carbonyl] hydroxylamine is comparably effective. These compounds also inactivate the class A TEM -lactamase. A crystal structure of the inactivated AmpC enzyme, another class C -lactamase, reveals that the active site has become cross-linked by a carbamate bridge spanning Ser64, the active site nucleophile, and Lys315, a conserved active site residue.
-lactamase inhibitors. N-Benzyloxycarbonyl-O-(phenoxycarbonyl) hydroxylamine, for example, inactivates the class C Enterobacter cloacae P99 -lactamase with a rate constant of 6.1 × 103 s-1 M-1; approximately two turnover events accompany the inhibition. N-Benzyloxycarbonyl-O-[(3-carboxyphenoxy)carbonyl] hydroxylamine is comparably effective. These compounds also inactivate the class A TEM -lactamase. A crystal structure of the inactivated AmpC enzyme, another class C -lactamase, reveals that the active site has become cross-linked by a carbamate bridge spanning Ser64, the active site nucleophile, and Lys315, a conserved active site residue.© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |