Tryptophan-rich antimicrobial peptides: comparative properties and membrane interactions.
The interaction of several tryptophan (Trp)-rich cationic antimicrobial peptides with membranes was investigated. These peptides included tritrpticin, indolicidin, lactoferricin B (Lfcin B), and a shorter fragment of lactoferricin (LfcinB4-9). The average environment of the Trp residues of these peptides was assessed from their fluorescence properties, both the wavelength of maximal emission as well as the red edge effect. The insertion of the peptides into vesicles of differing composition was examined using quenching of the Trp fluorescence, with both soluble acrylamide and nitroxide-labelled phospholipids as well as by chemical modification of the Trp residues with N-bromosuccinimide. The results were consistent with the Trp side chains positioned mostly near the membrane-water interface. The extent of burial of the Trp side chains appears to be greater in vesicles containing phospholipids with the anionic phosphatidylglycerol headgroup. Leakage of the aqueous contents of liposomes was also measured using the 8-aminonaphthalene-1,3,6-trisulfonic acid--p-xylene-bis-pyridinium bromide assay. Tritrpticin, which demonstrated the greatest red edge shift, also displayed the largest amount of leakage from liposomes. Taken together, the results illustrate that cationic Trp-rich antimicrobial peptides preferentially disrupt large unilamellar vesicles with a net negative charge following their insertion into the interfacial region of the phospholipid bilayer.
Schibli
David J
DJ
Department of Biological Sciences, University of Calgary, AB, Canada.
Epand
Raquel F
RF
Vogel
Hans J
HJ
Epand
Richard M
RM
D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism*; D002942:Circular Dichroism; D007700:Kinetics; D007781:Lactoferrin / Q000031:analogs & derivatives* / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000378:metabolism*
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D009842:Oligopeptides; D011726:Pyridinium Compounds; C402895:tritrpticin; C073143:indolicidin; C082171:lactoferricin B; D014364:Tryptophan; D007781:Lactoferrin