Synthesis and Characterization of the Therapeutic Potential of Antifungal Peptoid β-5

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Clark, Maria
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University Honors College, Middle Tennessee State University
Cryptococcus neoformans is a pathogenic yeast species that is one of the leading causes of Cryptococcal meningitis. This form of meningitis, which begins with the inhalation of yeast spores, has a significant mortality rate of 81% percent, with high incidence in those who are immunocompromised. Current antifungal treatments such as fluconazole and amphotericin B have detrimental side effects, leaving a significant need for better alternative treatments. Peptoids, which are mimics of the natural peptides found in living organisms, exhibit beneficial characteristics such as protease degradation evasion and therefore longer half-lives, offer an alternative route for antifungal compound development. Peptoid compounds discovered in our own lab, such as β-5, must be characterized by determining efficacy against pathogenic species such as C. neoformans as well as the toxicity of the compounds in the presence of mammalian cells. Herein, assays for determining these factors have shown that β-5 has low toxicity in several mammalian cell lines and significant and rapid inhibition of C. neoformans. These characteristics, which are linked to the compound’s structure, suggest that future investigation can focus on working to further enhance the compound’s overall efficacy through structural modification.