Investigation of a novel artificial antimicrobial peptide by fluorescence correlation spectroscopy: an amphipathic cationic pattern is sufficient for selective binding to bacterial type membranes and antimicrobial activity.
Fluorescence Correlation Spectroscopy (FCS) is used to study the interaction of a recently designed antimicrobial peptide, called V4, with LPS and lipids of varying head and tail groups. V4 is designed based on a known amphipathic cationic pattern BHPHB (B: basic; H: hydrophobic; P: polar residue, respectively) and shows a good combination of high antimicrobial activity, low cytotoxic activity and low hemolytic activity. It is shown that V4 has high binding affinity for LPS, which is the major component of the outer membrane of Gram-negative bacteria, and shows selectivity for negatively charged lipids in contrast to zwitterionic lipids at a low peptide/lipid ratio. At high peptide/lipid ratio, V4 can permeabilize vesicles composed of negatively charged lipids and eventually cause vesicle fusion. The identification of the amphipathic cationic pattern as the mediator of selectivity and antimicrobial activity could be a first step in the rational design of better antimicrobial peptides.
Yu
Lanlan
L
Department of Chemistry, National University of Singapore, Singapore.
Ding
Jeak Ling
JL
Ho
Bow
B
Wohland
Thorsten
T
D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000378:metabolism; D002138:Calibration; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism; D004058:Diffusion; D008050:Lipid A / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D015233:Models, Statistical; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence / Q000379:methods*; D055672:Static Electricity; D013997:Time Factors
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D002412:Cations; D008050:Lipid A; D008051:Lipid Bilayers; D008055:Lipids; D008070:Lipopolysaccharides; D010455:Peptides; C505331:antimicrobial peptide V4