title: Antimicrobial activity of doubly-stapled alanine/lysine-based peptides.
abstract: In this study, we examined the potential of Verdine's double-stapling system for the de novo design of amphipathic helical antimicrobial peptides. We designed, synthesized, and tested a prototypical doubly-stapled helix of an alanine/lysine based model sequence, which showed reasonable antimicrobial activities and highly increased proteolytic stability. We then show that its hemolytic activity as well as antimicrobial activities can be further manipulated through the systematic modifications. Overall, the preliminary results obtained from this study imply that the doubly-stapled helices of short peptides can serve as a highly promising scaffold for the rational design of potent, selective, and metabolically stable antimicrobial peptides that can combat against the growing problems of antibiotic-resistance.
authors.affiliation: College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Thuy T T
authors.initials: TT
authors.lastname: Dinh
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Do-Hee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Huy X
authors.initials: HX
authors.lastname: Luong
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Bong-Jin
authors.initials: BJ
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea. Electronic address: ywkim730r@dongguk.edu.
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Kim
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001773:Blood Cells / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides
keywords: Amphipathic peptides; Antimicrobial peptides; Proteolytic resistance; Stapled peptides; α-Helix