title: Investigation of the role of tryptophan residues in cationic antimicrobial peptides to determine the mechanism of antimicrobial action.
abstract: OBJECTIVE
  To understand the effects of Trp residues in linear antimicrobial peptides with α-helical conformations on cell permeation ability and membrane transduction efficacy.
  
  
  RESULTS
  A series of L-K6 analogues were designed and synthesized by replacing Ile or Leu with Trp at different positions on the hydrophobic face of L-K6. The antimicrobial and haemolytic activity and secondary structure of the designed Trp-containing peptides were assessed. In addition, the role of Trp in membrane disruption for these designed peptides was investigated. I1W, I4W and L5W demonstrated stronger activity than the other peptides against both Gram-positive and Gram-negative bacteria. All of the tested peptides preferentially interacted with negatively charged vesicles composed of phosphatidylglycerol (PG)/cardiolipin (CL) or PG/CL/phosphatidylethanolamine, and, to a lesser extent, with zwitterionic vesicles. I1W, I4W and L5W caused calcein release at 2·5 μmol l(-1) .
  
  
  CONCLUSIONS
  The position of Trp, rather than the number of Trp residues, in these peptides was an important factor in the antimicrobial activity. Trp residues were deeply inserted into negatively charged membranes but were largely exposed in aqueous buffer solution.
  
  
  CONCLUSIONS
  These Trp-containing peptides may represent good candidates for new antibiotic agents and for use in new therapeutic approaches.
authors.affiliation: Faculty of Life Science, Liaoning Normal University, Dalian, China.
authors.forename: X
authors.initials: X
authors.lastname: Bi
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: D
authors.initials: D
authors.lastname: Shang
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D014364:Tryptophan
keywords: antimicrobial activities; calcein-loaded liposomes; helicity; membrane; temporins; tryptophan