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Anna Dano, Biology, Gregory O'Brien, Biology, Victoire-Grace Karambizi, Biology
Faculty Mentor(s): Professor Sujit Suwal, Chemistry, Professor Olga S. Novikova, Biology
Multidrug-resistant bacteria is an emerging global threat that is demanding worldwide attention. There is an urgent need for the innovation of novel therapeutics to replenish conventional antibiotics regimens. Several host defense Anti-Microbial Peptide (AMP) having immunomodulatory properties are currently developed into an antibacterial agent to overcome this biological obstacle. However, such molecules are cytotoxic, susceptible to undergo enzymatic degradation, and expensive. Likewise, several AMP-biomimetics are used in clinical trials to combat potential epidemics due to the possible evolution of new bacterial strains. In our lab, we recently developed a new class arylureido peptoids (ArU) through solid-phase synthesis. We demonstrated that a functionally diverse ArU library can be generated by coupling commercially available primary amines and arylisocyanate using split & pool synthetic approach. We are currently testing the antibacterial properties of some of the ArU molecules against different strains of microbials - Escherichia coli and Staphylococcus aureus. We explored the size of the ArU-backbone by adding methylamine as the side chain of the oligomers. After successful optimization of the oligomer size, we diversified the sidechain, measured MIC, CFU and able to identify our hit molecule. We found MIC value of the hit molecule is comparable to ampicillin treatment, at least against E. Coli. Currently, we are pursuing in-vitro cytotoxicity assay of the hit molecule against a human cell.
Dano, Anna; O'Brien, Gregory; and Karambizi, Victoire-Grace, "Antibacterial Oligo-Arylureides" (2021). Physical Geography and Sciences. 22.