title: Modifications on amphiphilicity and cationicity of unnatural amino acid containing peptides for the improvement of antimicrobial activity against pathogenic bacteria.
abstract: The widespread natural sources-derived cationic peptides have been reported to reveal bacterial killing and/or growth-inhibiting properties. Correspondingly, a number of artificial peptides have been designed to understand antibacterial mechanism of the cationic peptides. These peptides are expected to be an alternative antibiotic against drug-resistant pathogenic bacteria because major antimicrobial mechanism of cationic peptides involves bacterial membrane disorder, although those availabilities have not been well evaluated. In this study, cationic peptides containing Aib were prepared to evaluate the availability as an antimicrobial agent, especially against representative pathogenic bacteria. Among them, BRBA20, consisting of five repeated Aib-Arg-Aib-Ala sequences, showed strong antibacterial activity against both Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Additionally, growth of Serratia marcescens and multidrug-resistant Pseudomonas aeruginosa, known as proteases-secreting pathogenic bacteria, were also completely inhibited by BRBA20 under 20 µg/ml peptide concentrations. Our results suggested availabilities of Aib-derived amphiphilicity and protease resistance in the design of artificial antimicrobial peptides. Comparing BRBA20 with BKBA20, it was also concluded that Arg residue is the preferred cationic source than Lys for antimicrobial action of amphiphilic helices.
authors.affiliation: Department of Chemistry, Kurume University School of Medicine, Kurume 830-0011, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Taira
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Kuwano
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Higashimoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kodama
mesh_terms: D000621:Aminoisobutyric Acids / Q000737:chemistry; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D002412:Cations; D002463:Cell Membrane Permeability / Q000187:drug effects; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012706:Serratia marcescens / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013501:Surface-Active Agents / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000621:Aminoisobutyric Acids; D023181:Antimicrobial Cationic Peptides; D002412:Cations; D008051:Lipid Bilayers; D013501:Surface-Active Agents