title: Disruption of interactions between hydrophobic residues on nonpolar faces is a key determinant in decreasing hemolysis and increasing antimicrobial activities of α-helical amphipathic peptides.
abstract: To design antimicrobial peptides with decrease pore-forming activity in eukaryotic (host) membranes, an amphipathic α-helical model peptide composed of Leu and Lys was modified to probe the balance in antimicrobial and hemolytic activities. Among analogues with broken hydrophobic interactions, L8N derivative exhibited an 8000-fold decrease in hemolytic activity and an eightfold improvement in antimicrobial activity, affording a 64 000-fold increase in therapeutic index against E. coli.
authors.affiliation: Department of Chemistry & Education, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 151-742 (Korea).
authors.forename: Mieon
authors.initials: M
authors.lastname: Son
authors.forename: Yuri
authors.initials: Y
authors.lastname: Lee
authors.forename: Heeyong
authors.initials: H
authors.lastname: Hwang
authors.forename: Soonsil
authors.initials: S
authors.lastname: Hyun
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Yu
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D017433:Protein Structure, Secondary; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides
keywords: amphiphilicity; antimicrobial peptides; hemolytic activity; hydrophobicity; α‐helicity