title: Investigations into the ability of an oblique alpha-helical template to provide the basis for design of an antimicrobial anionic amphiphilic peptide.
abstract: AP1 (GEQGALAQFGEWL) was shown by theoretical analysis to be an anionic oblique-orientated alpha-helix former. The peptide exhibited a monolayer surface area of 1.42 nm(2), implying possession of alpha-helical structure at an air/water interface, and Fourier transform infrared spectroscopy (FTIR) showed the peptide to be alpha-helical (100%) in the presence of vesicle mimics of Escherichia coli membranes. FTIR lipid-phase transition analysis showed the peptide to induce large decreases in the fluidity of these E. coli membrane mimics, and Langmuir-Blodgett trough analysis found the peptide to induce large surface pressure changes in monolayer mimics of E. coli membranes (4.6 mN.m(-1)). Analysis of compression isotherms based on mixing enthalpy (DeltaH) and the Gibbs free energy of mixing (DeltaG(Mix)) predicted that these monolayers were thermodynamically stable (DeltaH and DeltaG(Mix) each negative) but were destabilized by the presence of the peptide (DeltaH and DeltaG(Mix) each positive). The peptide was found to have a minimum lethal concentration of 3 mm against E. coli and was seen to cause lysis of erythrocytes at 5 mm. In combination, these data clearly show that AP1 functions as an anionic alpha-helical antimicrobial peptide and suggest that both its tilted peptide characteristics and the composition of its target membrane are important determinants of its efficacy of action.
authors.affiliation: Faculty of Science, University of Central Lancashire, Preston, UK.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Dennison
authors.forename: Leslie H G
authors.initials: LH
authors.lastname: Morton
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
authors.forename: Frederick
authors.initials: F
authors.lastname: Harris
authors.forename: David A
authors.initials: DA
authors.lastname: Phoenix
mesh_terms: D000595:Amino Acid Sequence; D000838:Anions / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D000838:Anions; D000890:Anti-Infective Agents; D008051:Lipid Bilayers; D009842:Oligopeptides