L-Tryptophan hydroxamic acid derivatives as Burkholderia pseudomallei IspF inhibitors
Muller, Chante Ashley
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Burkholderia pseudomallei is a Gram-negative bacterium that can cause a severe and potentially deadly infection called melioidosis. Typically found in tropical and subtropical regions of the world, this bacterium is considered a Tier 1 Select Agent by the CDC. A Tier 1 Select Agent can pose a severe threat to plants, animals, and humans. This bacterium utilizes the isoprenoid biosynthetic route called the 2-C-methyl-D-erythritol 4-phosphate, or MEP, pathway. This pathway is used by most bacteria, plants, and apicomplexan protozoa to produce two isoprenoid precursors, isopentyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are used by the bacterium to synthesize molecules that aid in cell membrane maintenance and aerobic and anaerobic respiration. The MEP pathway is an ideal pathway to inhibit since it is not found in humans and selective inhibition of an enzyme in this pathway could lead to new antibiotics with potentially fewer side effects in humans. This thesis focuses on the design, synthesis, and assay of small molecules to inhibit the fifth enzyme in the MEP pathway of Burkholderia pseudomallei , BpIspF.