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Infectious diseases cause millions of deaths each year. The top single disease killers include tuberculosis and diarrheal diseases. The diarrheal diseases caused by cholera toxin and E. coli heat-labile enterotoxin constitute a large part of the diarrhea-related deaths worldwide each year. While there are some efficacious drugs against Vibrio cholerae in the market, their resistance is developing quickly. We wish to develop synthetic molecules that could bind to CT with a high affinity to block the enzymatic reaction catalyzed by CT. We designed, synthesized and evaluated bisubstrate analogs targeting the active site of CT. The most potent inhibitor demonstrated an IC50 of around 40 M. It could serve as a promising drug to treat cholera. The second project is to use -helix mimetics for probing the protein-protein interactions of DosR. The main function of DosR is to mediate the transition of Mycobacteria tuberculosis into dormancy and may contribute to latency. Disruption of the dimerization of DosR could keep MTB in an active state, so that the existing drugs could treat them effectively. We employed small molecules and peptides as tools to achieve the goal.

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Guangtao Zhang received his B.S. in chemistry in 2000 from University of Science and Technology of China. He joined the graduate program at University of Washington and carried out his Ph.D. research with Professor Erkang Fan. His research interests centered on structure-based drug design, organic synthesis, and medicinal chemistry.

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