Interaction of filipin with dimyristoylphosphatidylcholine membranes studied by 2H-NMR, circular dichroism, electronic absorption and fluorescence.
Interaction of the pentene antibiotic filipin with dimyristoylphosphatidylcholine (DMPC) membranes has been monitored by 2H-NMR, circular dichroism (CD), electronic absorption and fluorescence in the temperature range 10 degrees to 60 degrees C. Interaction appears to depend on whether filipin is added before or after membrane formation and also upon the temperature of the system. When filipin is added to preformed DMPC large unilamellar vesicles (LUV), the association constants, as determined by electronic absorption are 39 x 10(3) M-1, 15 x 10(3) M-1 and 0.6 x 10(3) M-1 at 15 degrees, 30 degrees and 50 degrees C, respectively. Under identical conditions, CD spectra of bound filipin exhibit features characteristic of an aggregation over the whole temperature range. When filipin is incorporated in membranes during their preparation, the 2H-NMR spectra of deuterated DMPC indicate that the drug has a slight disordering effect on the lipid matrix below the temperature, Tc, of the gel-to-fluid phase transition and above Tc + 11 degrees C. Between these two temperature boundaries the system consists of two lipid regions of very different dynamic properties. One of the regions, which is attributed to a filipin-lipid complex, has the properties of gel-like lipids whereas the other has those of fluid-like lipids. The latter domain is however more ordered than the pure lipid at corresponding temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)
Milhaud
J
J
Laboratoire de Physique et Chimie Biomoléculaire (UA CNRS 198), Université Pierre et Marie Curie, Paris, France.
Mazerski
J
J
Bolard
J
J
Dufourc
E J
EJ
D000935:Antifungal Agents; D002942:Circular Dichroism; D003903:Deuterium; D004134:Dimyristoylphosphatidylcholine; D005372:Filipin; D005452:Fluoresceins; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008954:Models, Biological; D008968:Molecular Conformation; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics
D000935:Antifungal Agents; D005452:Fluoresceins; D008567:Membranes, Artificial; C024098:6-carboxyfluorescein; D005372:Filipin; D003903:Deuterium; D004134:Dimyristoylphosphatidylcholine