Antibiotic resistance is a prevalent issue due to misuse and subsequent rise of bacterial resistance mechanisms. Anti-virulence methods block bacterial virulence factors, like adhesion, without killing the bacteria, providing an alternative to antibiotic treatment. Adhesion occurs when carbohydrates on a host cell become bound to bacteria, this is a virulence factor that leads to colonization and biofilm formation, making infections harder to treat. Creating anti-adhesion sugars, or inhibitors, to bind to bacteria making it incapable of adhering to a host cell is a promising anti-virulence method. GafD is a lectin in strains of <i>E. coli</i> that causes diarrheal infections and naturally binds to N-acetyl-ß-D-glucosamine (GlcNAc) found in the microvilli of intestinal epithelial cells. The goal of this project is to make derivatives of GlcNAc to serve as inhibitors of GafD-mediated <i>E. coli </i>adhesion. Modifications have been made at the nitrogen group of GlcNAc by reacting per-O-acetylated glucosamine with varying benzoyl chlorides to form aromatic amide derivatives. These derivatives are then transformed into the methyl glycoside and the remaining acetate groups are deprotected, producing modified GlcNAc compounds that can be tested for GafD binding. Modifications performed to date include synthesis of benzoyl, 4-trifluoromethylbenzoyl, N,N-dimethylaminobenzoyl and 3,5-bis(trifluoromethyl)benzoyl amides. Synthesized inhibitors will be assessed for binding affinity to GafD using an ELISA-like assay. For use as an immobilized control ligand in the binding assay, progress has also been made in the preparation of GlcNAc for conjugation to bovine serum albumin (BSA) through a multi-step sequence.

Synthesis of anti-adhesion carbohydrates against bacterial biofilms

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