Title:
Developing Anti-Adhesion Derivatives of N-acetylglucosamine for the Inhibition of Biofilm Formation
Author(s):
Afton Johnston
Author Email:
ajohnst2@unca.edu
Department:
CHEMISTRY & BIOCHEMISTRY
Faculty Mentor(s):
Caitlin McMahon
Abstract / Summary:
Antibiotic resistance has become a rising public health issue over the past several decades, with an urgent need to find a solution. Inhibiting the formation of biofilms would be an alternative anti-virulence strategy for treating infections while decreasing the spread of antibiotic resistance. Anti-virulence strategies utilize inhibitors that inhibit virulence instead of killing the bacterium, reducing the likelihood of bacteria developing resistance to the moleculesOne bacterial virulence factor is adhesion; during colonization, bacterial pathogens adhere to host cells to avoid elimination by clearance mechanisms. Adhesion is mediated by bacterial surface lectins, in the form of elongated protein appendages, highly specific to carbohydrates on the host cell. We aim to mimic the carbohydrates found on the host cell to bind to the lectins on the bacterial pathogen and block adhesion. To achieve this, analogs of N-acetylglucosamine (GlcNAc) have been synthesized to target the F17G/GafD lectins found on strains of E. coli. Due to carbohydrates exhibiting a relatively weak adhesion, focusing on increasing binding affinity is our main goal. In this study, modifications have been made to the anomeric position of GlcNAc to increase protein-carbohydrate contacts through hydrogen bonding and aromatic interactions, in an effort to create higher affinity inhibitors. Three derivatives have been synthesized, achieved by the glycosidation of N-acetylglucosamine with 5-phenyl-1-pentanol, 2-phenylethyl alcohol, and 3-phenyl-1-propanol.
Publication Date:
May-14-2024
Documents: