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RUSH UNIVERSITY MEDICAL CENTER

Schistosomiasis is an important tropical parasitic human disease. Although an effective anti-schistosome drug is in use, it is estimated that 200 million people are infected, 20 million individuals suffer severe disease symptoms, and 280,000 people die annually from schistosomiasis. Transmission rates have changed little with the use of the drug and there is evidence for the development of drug resistant parasites. Because there is currently no suitable alternative therapy available there is an urgent need for the development of novel antischistosomal agents. In this application we propose to focus on novel parasite enzyme, phytochelatin synthase, which is found in the parasite, but not its host, as a target for antischistosomal drug development. Phytochelatins, which have been well characterized in plants where they serve as the primary means of sequestering toxic heavy metals, are oligopeptides synthesized from glutathione by PCS. More recently, PCS have been shown to be involved in the catabolism of glutathione-conjugated xenobiotics. The goal of this R21 exploratory/developmental grant proposal is to characterize the potential as a drug target of this unique, schistosome-specific protein. Our long-term goals are to identify parasite pathways that are different form host and to exploit these differences as targets for rational drug design for schistosomiasis control.

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