title: Peptoid Library Agar Diffusion (PLAD) Assay for the High-Throughput Identification of Antimicrobial Peptoids.
abstract: Rapid emergence of antimicrobial resistant organisms necessitates equally rapid methods for the development of new antimicrobial compounds. Of recent interest have been mimics of antimicrobial peptides known as antimicrobial peptoids, which exhibit similar potency to the former but with improved proteolytic stability. Presented herein is a high-throughput method to screen libraries of antimicrobial peptoids immobilized on beads embedded into solid media. Termed the peptoid library agar diffusion (PLAD) assay, this assay allows for individual chemical manipulation of two identical peptoid strands. One strand can be released to diffuse out from a solid support bead and interact with the microorganism during screening. The other strand can be cleaved after screening from beads showing strong antimicrobial activity and analyzed by mass spectrometry to deconvolute the structure of the peptoid. This method was applied to a small library of peptoids to identify an antimicrobial peptoid with modest efficacy against the ESKAPE pathogens.
authors.affiliation: Middle Tennessee State University , Department of Chemistry, 1301 East Main Street, Murfreesboro, Tennessee 37132, United States.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Fisher
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: Ashley E
authors.initials: AE
authors.lastname: Corson
authors.affiliation: Middle Tennessee State University , Department of Chemistry, 1301 East Main Street, Murfreesboro, Tennessee 37132, United States.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Bicker
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000302:isolation & purification; D057166:High-Throughput Screening Assays / Q000379:methods; D013058:Mass Spectrometry; D008863:Microspheres; D019151:Peptide Library; D034444:Peptoids / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents; D019151:Peptide Library; D034444:Peptoids
keywords: antimicrobial; combinatorial library; high-throughput; peptoids