Fan, Erkang, Ph.D.
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.
Minke, W.E., Hong, F., Verlinde, C.L.M.J., Hol, W.G.J., and Fan, E. (1999) Using a galactose library for
exploration of a novel hydrophobic pocket in the receptor binding site of the Escherichia coli heat-labile
enterotoxin. J. Biol. Chem. 274: 33469-33473.
Ghosh, A.K. and Fan, E. (2000) A novel method for sequence independent incorporation of
activated/protected cysteine in Fmoc solid phase peptide syntheses. Tet. Lett. 41:165-168.
Fan, E., Zhang, Z., Minke, W.E. , Hou, Z. , Verlinde, C.L.M.J., and Hol, W.G.J. (2000) High-affinity
pentavalent ligands of Escherichia coli heat-labile enterotoxin by modular structure-based design. J. Am.Chem. Soc. 122:2663-2664.