title: Evaluating the Effect of Peptoid Lipophilicity on Antimicrobial Potency, Cytotoxicity, and Combinatorial Library Design.
abstract: Growing prevalence of antibiotic resistant bacterial infections necessitates novel antimicrobials, which could be rapidly identified from combinatorial libraries. We report the use of the peptoid library agar diffusion (PLAD) assay 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. Furthermore, this work demonstrates the utility of the PLAD assay in rapidly evaluating the effect of molecular property changes in similar libraries.
authors.affiliation: Middle Tennessee State University , Department of Chemistry, 1301 East Main Street, Murfreesboro, Tennessee 37132, United States.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Turkett
authors.affiliation: Middle Tennessee State University , Department of Chemistry, 1301 East Main Street, Murfreesboro, Tennessee 37132, United States.
authors.forename: Kevin L
authors.identifier: 0000-0002-8638-971X
authors.initials: KL
authors.lastname: Bicker
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D020650:Combinatorial Chemistry Techniques; D013293:Enterococcus faecalis / Q000187:drug effects; D057166:High-Throughput Screening Assays; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D034444:Peptoids / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D034444:Peptoids; D054852:Small Molecule Libraries
keywords: ESKAPE; antimicrobial; combinatorial library; high-throughput; lipophilicity; peptoid