Interaction of trichorzianines A and B with model membranes and with the amoeba Dictyostelium.
Trichorzianines A (TA) and B (TB) are microheterogeneous mixtures of antibiotic nonadecapeptides of the peptaibol class which interact with lipidic membranes and modify their permeability properties. The TB differ from the TA by replacement of the Gln-18 by a Glu, giving rise to a C-terminal negative charge at neutral pH. The role of this charge on the trichorzianine-lipid interaction was investigated with model membranes by fluorescence spectroscopy and the results were correlated with the biological activity toward the amoeba Dictyostelium discoideum. The interaction of the acidic trichorzianine TB IIIc (Glu-18) with phospholipid bilayers and the subsequent induced permeability were weaker than that exhibited by the uncharged TA IIIc (Gln-18) and MeTB IIIc (TB IIIc monomethyl ester). The unfavourable effect of the negative charge in TB IIIc was strongly enhanced by incorporation of cholesterol in the bilayer. Similarly, TA IIIc as well as MeTB IIIc induced growth inhibition and lysis of the amoeba Dictyostelium at four times lower concentrations than TB IIIc. The results suggested that the interaction of trichorzianines with the phospholipid bilayer and the subsequent modifications of permeability were involved in the inhibitory properties and cell lysis induced by trichorzianines toward Dictyostelium.
el Hajji
M
M
Laboratoire de Chimie, UA 401 CNRS, Muséum National d'Histoire Naturelle, Grenoble, France.
Rebuffat
S
S
Le Doan
T
T
Klein
G
G
Satre
M
M
Bodo
B
B
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents; D002463:Cell Membrane Permeability / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D004023:Dictyostelium / Q000187:drug effects*; D005452:Fluoresceins / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D008969:Molecular Sequence Data; D054848:Peptaibols; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
D000900:Anti-Bacterial Agents; D005452:Fluoresceins; D005656:Fungal Proteins; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D054848:Peptaibols; D010455:Peptides; C058494:trichorzianine B; C024098:6-carboxyfluorescein; C039715:trichorzianine; C049370:trichorzianine A IIIc; D002784:Cholesterol