title: Dynamic turn conformation of a short tryptophan-rich cationic antimicrobial peptide and its interaction with phospholipid membranes.
abstract: Cationic antimicrobial peptides are promising sources for novel therapeutic agents against multi-drug-resistant bacteria. HHC-36 (KRWWKWWRR) is a simple but effective antimicrobial peptide with similar or superior activity compared with several conventional antibiotics. In this biophysical study, unique conformational properties of this peptide and some of its analogs as well as its interaction with lipid membranes are investigated in detail. Circular dichroism (CD) and molecular dynamics modeling studies of HHC-36 in different environments reveal a dynamic amphipathic structure composed of competing turn conformations with free energies lower than that of the unfolded state, implying a strong influence of tryptophan interactions in formation of the turns. CD spectra and gel electrophoresis also show strong evidence of self-association of this peptide in aqueous milieu and interaction with both neutrally and negatively charged lipid membrane systems. Isothermal titration calorimetry and acrylamide fluorescence quenching experiments emphasize the preference of HHC-36 for negatively charged vesicles. In addition, dye leakage experiments suggest that this peptide functions through a surface-associated mechanism with weak lytic activity against bacterial model membranes.
authors.affiliation: Department of Chemistry, Wilfrid Laurier University , 75 University Avenue West, Waterloo, Ontario N2L 3C5, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Nichols
authors.forename: Miljan
authors.initials: M
authors.lastname: Kuljanin
authors.forename: Mostafa
authors.initials: M
authors.lastname: Nategholeslam
authors.forename: Tuan
authors.initials: T
authors.lastname: Hoang
authors.forename: Shaghayegh
authors.initials: S
authors.lastname: Vafaei
authors.forename: Bruno
authors.initials: B
authors.lastname: Tomberli
authors.forename: C G
authors.initials: CG
authors.lastname: Gray
authors.forename: Lillian
authors.initials: L
authors.lastname: DeBruin
authors.forename: Masoud
authors.initials: M
authors.lastname: Jelokhani-Niaraki
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010743:Phospholipids / Q000378:metabolism*; D017433:Protein Structure, Secondary; D014364:Tryptophan / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010743:Phospholipids; D014364:Tryptophan