Synthesis and Characterization of Antifungal Peptoid Dendrimers

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Johnson, Matthew
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University Honors College, Middle Tennessee State University
Currently the rate of fungal infections across the globe is increasing and given heightened rates of resistance to a limited number of treatment options, new anti-fungal agents are desperately needed. Opportunistic fungi such as Cryptococcus neoformans are a major part of the problem, as they infect immunocompromised individuals. A vast majority of the antifungals on the market exhibit a variety of toxicities as well as drug interactions that prevent symbiotic treatment modalities. Peptoids are peptidomimetics that are Nsubstituted glycine oligomers and have been shown to have promise as antimicrobial agents due to their proteolytic stability, low hemolytic activity, quick killing kinetics, minimal mammalian toxicity, and nonspecific mode of action. Given this, our group has developed a promising antifungal peptoid (RMG8-8) for treatment of C. neoformans and to attempt to improve the activity of this molecule, we have explored a novel display of RMG8-8: peptoid dendrimers. Antimicrobial peptide (AMP) dendrimers have been reported to have hyper-potency against a wide variety of yeasts and their absorption and bioavailability improved due to increased steric hindrance, providing in vivo stability. Due to structural similarities between peptides and peptoids, these benefits are likely to apply to peptoid dendrimers. Specifically, several generations of RMG8-8 dendrimers have been synthesized displaying varying copies of the peptoid and will be tested for antifungal activity and mammalian cytotoxicity.