Research Assistant Professor
The rapid advancement of combinatorial chemistry offers chemists unprecedented power to quickly and efficiently generate large number of diverse molecules for screening desired properties. We are actively engaged in using combinatorial chemistry to generate and optimize lead compounds in a structure-based drug design cycle.
One specific example is to design ultra-high affinity inhibitors for the receptor recognition process of cholera toxin (CT) and E. coli heat-labile enterotoxin (LT). CT and LT belong to a so-called AB5 family of bacterial toxins. Their symmetrical pentameric B subunits are responsible for cell surface receptor recognition, a critical step for the toxins’ invasion into host cells. Based on the the high-resolution crystal structures of either CT or LT, we are trying to design and synthesize simple sugar molecules which can have affinities similar to the toxins’ nature glycolipid head group. Then, by linking up to five copies of these small inhibitors together, we can gain several orders of magnitude further in affinity. This strategy will allow us to develop effective therapeutics against both CT and LT.