A methylenebis(sulfonamide) linked NAD analogue has been designed to circumvent the metabolically unstable, ionic nature of the natural pyrophosphate linkage. This NAD analogue is assembled through two Mitsunobu reactions of a methylenebis(sulfonamide) linker with two protected nucleosides. A 2,4-dimethoxybenzyl group is used as a sulfonamide protective group, which allows facile removal under mildly acidic conditions. This NAD analogue inhibits IMPDH at low micromolar concentration.
Bibliographical noteFunding Information:
These studies were funded by the Center for Drug Design, University of Minnesota, and USDOD ARMY Grant W81XWH-05-01-0216.
Copyright 2009 Elsevier B.V., All rights reserved.
- Inosine monophosphate dehydrogenase
- NAD analogue
- Pyrophosphate mimics