Chemical Biology & Spectroscopy
Research in the Tonge Group is focused on understanding how proteins control and modulate the properties of small molecule ligands. We are interested in understanding the fundamental aspects of enzyme catalysis and in determining how enzymes cause and stabilize charge rearrangement. Some of the enzymes we study are drug targets in pathogens such as Mycobacterium tuberculosis, Francisella tularensis, Burkholderia pseudomallei and methicillin-resistant Staphylococcus aureus (MRSA). We use mechanistic information to design and synthesize high affinity enzyme inhibitors that have long residence times on their targets based on the knowledge that drug-target residence time is a critcal factor for in vivo antibacterial activity. The long residence time inhibitors are also being used to image bacterial populations in humans using positron emission tomography. In addition to enzymes, we are also interested in understanding how fluorescent proteins, such as green fluorescent protein (GFP), control the formation and fluorescence of the embedded chromophore. Studies on GFP are now being extended to other light activated proteins such as AppA, a BLUF domain antirepressor from the photosynthetic bacterium Rhodobacter sphaeroides.