Joy M Blain, Dakota L Grote, Sydney M Watkins, Gashaw M Goshu, Chanté Muller, James L Gorman, Gina Ranieri, Richard L Walter, Heike Hofstetter, James R Horn, Timothy J Hagen
The enzyme 2-methylerythritol 2,4-cyclodiphosphate synthase, IspF, is essential for the biosynthesis of isoprenoids in most bacteria, some eukaryotic parasites, and the plastids of plant cells. The development of inhibitors that target IspF may lead to novel classes of anti-infective agents or herbicides. Enantiomers of tryptophan hydroxamate were synthesized and evaluated for binding to Burkholderia pseudomallei (Bp) IspF. The L-isomer possessed the highest potency, binding BpIspF with a KD of 36 µM and inhibited BpIspF activity 55% at 120 µM...
July 20, 2021: Bioorganic & Medicinal Chemistry Letters