Design and Screening of Antimicrobial Peptoid Libraries

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Turkett, Jeremy
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Middle Tennessee State University
Growing prevalence of antibiotic resistant bacterial infections necessitates the development of novel antimicrobials, which could be rapidly identified from combinatorial libraries. Peptoids are a class of antimicrobial peptidomimetics which are uniquely suited for library synthesis. The research presented utilizes the peptoid library agar diffusion (PLAD) assay1 to screen peptoid libraries against the ESKAPE pathogens, including the optimization of assay conditions for each pathogen. Work presented here focuses on the tailoring of combinatorial peptoid library design through a detailed study of how peptoid lipophilicity relates to antibacterial potency and mammalian cell toxicity. The information gleaned from this optimization was then applied using the aforementioned screening method to examine the relative potency of peptoid libraries against Staphylococcus aureus, Acinetobacter baumannii, and Enterococcus faecalis prior to and following functionalization with long alkyl tails. The data indicate that overall peptoid hydrophobicity and not simply alkyl tail length is strongly correlated with mammalian cell toxicity.2 The necessity of peptoid library lipophilicity being illuminated by the study, library development shifted to addressing the difficulties presented by single bead analysis via ESI tandem MS (MS/MS).
Antibiotic, Antimicrobial, Combinatorial library, Peptidomimetics, Peptoid