Discovery and Study of the Binding Epitopes of Novel Urease Inhibitors by STD-NMR Spectroscopy and Biochemical Analyses

In this study, Saturation Transfer Difference NMR (STD NMR) was employed for the first time to detect the binding epitopes of new inhibitors of the enzyme urease. Inhibition of urease is recognized as an important approach towards the treatment of ulcer, urolithiasis and related diseases. During the current study, STD-NMR was used as a tool for the identification of structural features responsible for inhibition of urease enzyme at the atomic levels. This approach, combined with mechanism-based biochemical assay, is specially suited for the discovery and optimization of potent inhibitors of enzymes. Urease from Jack beans was used for epitope mapping of inhibitors, i.e. flavonoid glycosides, hypoxanthine and benzodioxane derivatives and STD-NMR results were compared with the results of kinetic studies.