Interaction of pleurocidin and its analogs with phospholipid membrane and their antibacterial activity.
A 25-mer cationic peptide pleurocidin, isolated from the winter flounder, has broad antibacterial activity. To clarify the structure-activity relationship, its properties and biological activity were examined. CD measurements showed that pleurocidin took an alpha-helical structure in the presence of DOPC/DOPG (3:1, anionic) vesicles. Very weak hemolytic activity of pleurocidin was observed and its antibacterial activity was moderate. Tryptophan fluorescence shift measurements showed that pleurocidin interacted weakly with a neutral phospholipid, but strongly with an acidic phospholipid. The peptide exhibited weak dye-leakage activity for DOPC (neutral) vesicles and moderate activity for acidic vesicles. From experiments on dye-leakage activity and membrane translocation of the peptide, it seemed likely that pleurocidin, like magainin 2, forms pores in the lipid membrane. A study of amino acid substitution in pleurocidin revealed that alpha-helicity, rather than hydrophobicity, affects the properties and activity of the peptide.
Yoshida
K
K
Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, Japan.
Mukai
Y
Y
Niidome
T
T
Takashi
C
C
Tokunaga
Y
Y
Hatakeyama
T
T
Aoyagi
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002942:Circular Dichroism; D029941:Fish Proteins; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008567:Membranes, Artificial; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000737:chemistry
D000900:Anti-Bacterial Agents; D029941:Fish Proteins; D008567:Membranes, Artificial; D010455:Peptides; D010743:Phospholipids; D011506:Proteins; C105851:pleurocidin; D014364:Tryptophan