Use of Transporters to Selectively Deliver Agents to Trypanosomes

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Human African trypanosomiasis (HAT), more commonly known as sleeping sickness is prevalent in sub-Saharan Africa and is inevitably fatal unless treated. It is caused by single-celled parasites, which live in the blood stream and eventually invade the brain. The current drugs available to treat the disease are unsatisfactory, due to issues such as toxicity, resistance, difficulty in administration of the drugs, lack of efficacy and cost. In this basic science proposal we aim to start the development of new drugs. The parasites which cause HAT require nutrients from the human host for their survival. To take up these nutrients, they have transporters in their cell membranes. Some of these transporters are very different from those found in human cell membranes. One particular transporter, usually involved in carrying important chemicals called purines into cells, can be tricked into carrying other classes of molecules (transporter motifs), which are not carried by mammalian purine transporters. We aim to develop new classes of drugs to treat HAT by attaching compounds that will kill parasites to these transporter motifs. These compounds should then selectively kill the parasites. The project will consist of design and preparation of these compounds, evaluation and studying how the compounds work.