NOVEL ASSAY METHODS FOR ETHYLENE GLYCOL TOXICITY

Not Available Recent discoveries of plant-like organelles in Plasmodium falciparum, the organism that causes malaria, provide potential new avenues toward treatment and prevention of this deadly disease. More specifically, it is now known that the Shikimate Pathway, an enzymatic pathway that provides essential aromatics, is vital to the survival of P. falciparum. By blocking any of the seven enzymes in this pathway, it is possible to attenuate growth of the organism. Since these enzymes are not present in humans, their blockage presents an opportunity to effectively and selectively treat the disease without harm to human cells. We propose to clone the recently discovered P. falciparum charismata synthase (enzyme #7 of the Shikimate pathway) in E. Coli, by known procedures. Using the resulting product, we will then develop a prototype high throughput assay, which will lead to the development (in Phase II) of a major screening program of combinatorial libraries of potential antimalarial drugs. BENEFITS: Safe and effective antimalarials could make a significant impact in human health. The proposed genomics/combinatorial chemistry approach not only provides potential new antimalarials, but validates a method of much broader application to drug discovery.