Using a galactose library for exploration of a novel hydrophobic pocket inthe receptor binding site of the Escherichia coli heat-labile enterotoxin

The binding of the B subunits of Escherichia coli heat-labile enterotoxin ( LT) to epithelial cells lining the intestines is a critical step for the to xin to invade the host. This mechanism suggests that molecules which posses s high affinity to the receptor binding site of the toxin would be good lea ds for the development of therapeutics against LT. The natural receptor for LT is the complex ganglioside GM1, which has galactose as its terminal sug ar. A chemical library targeting a novel hydrophobic pocket in the receptor binding site of LT was constructed based on galactose derivatives and scre ened for high affinity to the receptor binding site of LT. This screening i dentified compounds that have 2-3 orders of magnitude higher affinity towar d the receptor binding site of LT than the parent compound, galactose. The present findings will pave the way for developing simple and easily synthes izable molecules, instead of complex oligosaccharides, as drugs and/or prop hylactics against LT caused disease.