Antibiotic resistance is a rapidly growing concern and it is becoming increasingly important to develop new ways to treat bacterial infections. Anti-virulence strategies focus on disarming bacteria rather than killing them, putting less selective pressure on the bacteria and making it less likely bacteria will become resistant to the treatments. One virulence factor is the formation of biofilms, which occurs when lectins on the surface of bacteria bind to carbohydrates on the host cell. By targeting inhibition, the cells would not be able to aggregate and bind to host cells, effectively making the bacteria less virulent. In some strains of E. coli, this process involves the lectin F17G/GafD on the bacterial cell and the carbohydrate N-acetyl β-D Glucosamine (GlcNAc) on the epithelial host cell. Here N-acetyl β-D Glucosamine (GlcNAc)-derived inhibitors for the F17G/GafD lectins on E. coli are synthesized. To synthesize derivatives, GlcNAc pentaacetate is used to allow for selective modification of the anomeric position. The acetate protecting groups are then removed to yield the final product. Benzyl, phenyl, hexyl, and butyl glycosides have been successfully synthesized. In tandem with the synthesis, an expression and purification protocol for GafD was being optimized, utilizing both His-tag cobalt affinity and GlcNAc binding affinity for purification. Conditions have been optimized for an ELISA competitive binding assay, using laminin as an immobilized ligand. These tools will enable the development of strong inhibitors of bacterial adhesion for investigation as anti-virulence molecules.

Synthesis and evaluation of anti-adhesion carbohydrates for E. coli lectin F17G

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