Trypanosoma cruzi is the etiological agent of Chagas' disease, a chronic debilitating incurable illness afflicting millions of people in Latin America. Neuraminidase/trans-sialidase (TSA) is a T. cruzi protein that mediate invasion by promoting parasite attachment to cells, immunosuppression, and upregulation of parasite invasion. Inhibition of TSA activity suppresses T. cruzi infection. TSA is therefore a target for the chemotherapy of Chagas' disease. The goal of this project is to find TSA inhibitor(s) (Phase I), that can be optimized to treat T. cruzi infection (Phase II and III). For this purpose a carbohydrate-based combinatorial library will be screened against TSA. The screening relies on a high throughput assay developed for the project. The chance of success for the project is very high because two sugar compounds, out of 15,000 already screened, inhibit TSA activity at the low mu M range. An additional 85,000 compounds need to be screened against TSA. Thus, chances are, more than 2 TSA inhibitors will be identified and characterized at the end of this Phase I project. These compounds should form the basis for the derivatization of compounds with greater affinity for TSA. The TSA inhibitors are great drug candidates, to be tested in Phase III, hopefully in collaboration with a pharmaceutical company. PROPOSED COMMERCIAL APPLICATIONS: Chagas' disease is a chronic, debilitating disease afflicting millions of people in this hemisphere. There are no vaccines nor drugs that cure Chagas' disease. A drug to treat Chagas' disease is sorely needed. Such drug should have significant marketability in the Americas
