Enediol mimics as inhibitors of the D-arabinose 5-phosphate isomerase (KdsD) from Francisella tularensis.

Article Details

Citation

Yep A, Sorenson RJ, Wilson MR, Showalter HD, Larsen SD, Keller PR, Woodard RW

Enediol mimics as inhibitors of the D-arabinose 5-phosphate isomerase (KdsD) from Francisella tularensis.

Bioorg Med Chem Lett. 2011 May 1;21(9):2679-82. doi: 10.1016/j.bmcl.2010.12.066. Epub 2010 Dec 19.

PubMed ID
21236668 [ View in PubMed
]
Abstract

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 muM, is the most potent KdsD inhibitor reported to date.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
4-Phospho-D-erythronohydroxamic acidRibose-5-phosphate isomerase BKi (nM)400000N/AN/ADetails
4-Phospho-D-erythronohydroxamic acidRibose-5-phosphate isomerase BKi (nM)57000N/AN/ADetails
Phosphoglycolohydroxamic AcidTriosephosphate isomeraseKi (nM)4000N/AN/ADetails