Virtual fragment screening for novel inhibitors of 6-phosphogluconate dehydrogenase.

ABSTRACT: The enzyme 6-phosphogluconate dehydrogenase is a potential drug target for the parasitic protozoan Trypanosoma brucei, the causative organism of human African trypanosomiasis. This enzyme has a polar active site to accommodate the phosphate, hydroxyl and carboxylate groups of the substrate, 6-phosphogluconate. A virtual fragment screen was undertaken of the enzyme to discover starting points for the development of inhibitors which are likely to have appropriate physicochemical properties for an orally bioavailable compound. A virtual screening library was developed, consisting of compounds with functional groups that could mimic the phosphate group of the substrate, but which have a higher pKa. Following docking, hits were clustered and appropriate compounds purchased and assayed against t

SUBMITTER: Ruda GF 

PROVIDER: S-EPMC2939770 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature