Enediol mimics as inhibitors of the d-arabinose 5-phosphate isomerase (KdsD) from Francisella tularensis
✍ Scribed by Alejandra Yep; Roderick J. Sorenson; Michael R. Wilson; H.D. Hollis Showalter; Scott D. Larsen; Paul R. Keller; Ronald W. Woodard
- Book ID
- 104005242
- Publisher
- Elsevier Science
- Year
- 2011
- Tongue
- English
- Weight
- 274 KB
- Volume
- 21
- Category
- Article
- ISSN
- 0960-894X
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✦ Synopsis
We explored the D-arabinose 5-phosphate isomerase (KdsD, E.C. 5.3.1.13) from Francisella tularensis, a highly infectious gram-negative pathogen that has raised concern as a potential bioweapon, as a target for the development of novel chemotherapeutics. F. tularensis KdsD was expressed in Escherichia coli from a synthetic gene, purified, and characterized. A group of hydroxamates designed to be mimics of the putative enediol intermediate in the enzyme's catalytic mechanism were prepared and tested as inhibitors of F. tularensis KdsD. The best inhibitor, which has an IC(50) of 7 μM, is the most potent KdsD inhibitor reported to date.