title: Influence of hydrophobic residues on the activity of the antimicrobial peptide magainin 2 and its synergy with PGLa.
abstract: Magainin 2 (MAG2) and PGLa are two related antimicrobial peptides found in the skin of the African frog Xenopus laevis with a pronounced synergistic activity, which act by permeabilizing bacterial membranes. To probe the influence of hydrophobic peptide-lipid and peptide-peptide interactions on the antimicrobial activity and on synergy, the sequence of MAG2 was modified by replacing single amino acids either with a small alanine or with the stiff and bulky hydrophobic 3-(trifluoromethyl)-L-bicyclopent-[1.1.1]-1-ylglycine side chain. The minimum inhibitory concentration of 14 MAG2 analogs was strongly influenced by these single substitutions: the antimicrobial activity was consistently improved when the hydrophobicity was increased on the hydrophobic face of the amphiphilic helix, while the activity decreased when the hydrophobicity was reduced. The synergy with PGLa, on the other hand, was rather insensitive to mutations of hydrophobic residues. It thus seems that the antimicrobial effect of MAG2 on its own depends strongly on the hydrophobicity of the peptide, while the synergy with PGLa does not depend on the overall hydrophobicity of MAG2.
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Biological Interfaces (IBG-2), POB 3640, 76021, Karlsruhe, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Strandberg
authors.forename: Jonathan
authors.initials: J
authors.lastname: Zerweck
authors.forename: Diana
authors.initials: D
authors.lastname: Horn
authors.forename: Günther
authors.initials: G
authors.lastname: Pritz
authors.forename: Marina
authors.initials: M
authors.lastname: Berditsch
authors.forename: Jochen
authors.initials: J
authors.lastname: Bürck
authors.forename: Parvesh
authors.initials: P
authors.lastname: Wadhwani
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
mesh_terms: D019943:Amino Acid Substitution; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D002942:Circular Dichroism; D004357:Drug Synergism; D057927:Hydrophobic and Hydrophilic Interactions; D054806:Magainins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D017433:Protein Structure, Secondary; D029867:Xenopus Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054806:Magainins; D029867:Xenopus Proteins; C045866:peptide-Gly-Leu-amide; C053301:magainin 2 peptide, Xenopus
keywords: circular dichroism; hemolysis; magainin 2 and PGLa; membrane-active antimicrobial peptides; minimum inhibitory concentration; synergistic activity