title: Short antimicrobial lipo-α/γ-AA hybrid peptides.
abstract: The last two decades have seen the rise of antimicrobial peptides (AMPs) to combat emerging antibiotic resistance. Herein we report the solid-phase synthesis of short lipidated α/γ-AA hybrid peptides. This family of lipo-chimeric peptidomimetics displays potent and broad-spectrum antimicrobial activity against a range of multi-drug resistant Gram-positive and Gram-negative bacteria. These lipo-α/γ-AA hybrid peptides also demonstrate high biological specificity, with no hemolytic activity towards red blood cells. Fluorescence microscopy suggests that these lipo-α/γ-AA chimeric peptides can mimic the mode of action of AMPs and kill bacterial pathogens via membrane disintegration. As the composition of these chimeric peptides is simple, therapeutic development could be economically feasible and amenable for a variety of antimicrobial applications.
authors.affiliation: Department of Chemistry, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620 (USA).
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Li
authors.forename: Christina
authors.initials: C
authors.lastname: Smith
authors.forename: Haifan
authors.initials: H
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Teng
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Shruti
authors.initials: S
authors.lastname: Padhee
authors.forename: Torey
authors.initials: T
authors.lastname: Jones
authors.forename: Anh-My
authors.initials: AM
authors.lastname: Nguyen
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Cao
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides
keywords: Gram-negative bacteria; Gram-positive bacteria; antimicrobial peptides; hemolysis; resistance; solid-phase synthesis