Synthesis and Screening of Antimicrobial Peptoid Combinatorial Libraries Against the Fungi Aspergillus, Candida, and Cryptococcus

Abstract

Studies show there is an increasing rate of fungal infections; a theory for the shift seen in infection patterns may be due to the escalation of patients with immunecompromising diseases. Treatments for fungal genera, such as Aspergillus, Candida, and Cryptococcus, carry many risks, including high toxicity levels that result in gastrointestinal complications, and hepatitis, as well as, a chance of developing resistance to anti-fungal medicine. Antimicrobial peptides (AMPs) offer alternative therapies for these infections due to little to no toxicity to mammalian cells, as well as their ability to singularly target fungal cells. AMPs have proven to be very effective for antibacterial activity, and this research has expanded to use peptide compounds against other organisms, such as fungi and viruses. However, peptides are also easily degraded within the human body. This allows for them to easily be targeted and degraded by proteases before the AMPs can reach their targeted organisms. A likely alternative to this problem is the employment of peptide mimics called peptoids. Peptoids have a slight structural difference compared to peptides that allow for increased stability and an extended half-life while having the same or very similar actions to peptides. This research consists of alternative therapeutic treatments for combating antimicrobial resistance by synthesizing a diverse combinatorial library of peptoids. The purpose of this research is to optimize the techniques of synthesis, screening, and sequencing of viable antimicrobial peptoids from a combinatorial library. These methods will give a one-bead-one-compound library that can be successfully screened against fungal genera Aspergillus, Candida, and Cryptococcus. The one-bead-one-compound combinatorial library’s design will allow for hundreds of thousands of unique compounds to be synthesized and screened for anti-fungal properties in a few days. This will be an efficient way to determine other therapeutic options in dealing with anti-fungal drug resistant infections and high toxicity levels to mammalian cells.