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1. >128 >400 >128 Antifungal Activity of Helical b-Peptide NanorodsPaul F. Nealy, University of Wisconsin – Madison, NSEC, DMR 0425880 Amy Karlsson, William Pomerantz, Sean Palecek and Sam Gellman Thrust II researchers have recently identified structural and sequence parameters that lead to b-peptide nanorods that cause selective disruption of cell membranes in the pathogenic eukaryote Candida albicans. b-Peptide nanorods have the potential to improve upon the activity of a-peptide antifungal agents as a result of more predictable and stable secondary structure, unique opportunities to tune physical and chemical properties of the oligomers, and resistance to enzymatic degradation. Several nanorod properties that lead to antifungal activity have been identified, including stable helical secondary structure, global amphilicity of hydrophobic and cationic residues, and a length on the order of the thickness of the lipid bilayer. In addition, specific b-peptide side chains affect activity and selectivity for fungal cells. Figure 1 compares the minimum b-peptide concentration needed to prevent fungal growth in suspension (MIC) with the concentration resulting in 50% lysis of red blood cells (HC50). The most selective nanorod [Y-(ACHC-ACHC-K)3] possesses high helical stability and global amphiphilicity. The majority of fungal infections are associated with biofilms deposited on implanted medical devices. b-peptide nanorods can prevent biofilm formation at their MIC against cells in suspension, but require concentration of 2-10 times their MIC to disrupt intact biofilms in vitro. Efforts are underway to determine b-peptide structural factors that will improve efficacy against these biofilms. Figure: Selectivity of b-peptides for C. albicans (MIC) vs red blood cells (HC50). Nanorods in the lower right quadrant possess low hemolysis at concentrations that prevent fungal growth.