Studies on the biological properties of polyene antibiotics: Comparison of other polyenes with filipin in their ability to interact specifically with sterol

Abstract

SUMMARYI. The interaction of the five polyene antibiotics filipin, etruscomycin, pimaricin, nystatin and amphotericin B with sterol, primarily free, liposomal and membrane bound cholesterol has been examined. Each of these antibiotics has a characteristic ultraviolet absorption spectrum in aqueous or organic solvents with three or four ultraviolet absorption maxima.Addition of free cholesterol to aqueous solutions of these antibiotics results in a change of the ratio of the ultraviolet absorbance maxima. The order of effectiveness of interaction with cholesterol as judged by this criterion was filipin, amphotericin B, etruscomycin and pimaricin.2. The same alteration in ultraviolet absorption spectra of filipin, etruscomycin and amphotericln B observed with addition of free cholesterol to aqueous solutions of these antibiotics also occurs upon addition of these antibiotics to liposomal, erythrocyte or Acholeplasma membrane bound cholesterol. No spectral change was found in membranes devoid of cholesterol. This spectral alteration of the antibiotic was accompanied by a binding of the antibiotic to the membrane. Both nystatin and pimaricin showed little change in spectrum with sterol in these systems, either the artificial or natural membranes which contained cholesterol.3. The structural requirements of the sterol for the spectral change with filipin, etruscomycin and amphotericin B include a planar sterol nucleus, an intact side chain at C-I 7 and a 3r-hydroxyl group. The spectral change was not affected by the pH except in the case of amphotericin B.4. Measurements by differential scanning calorimetry of the effect of these polyene antibiotics on the phase transition of lecithin and lecithin-cholesterol showed that all polyenes can reduce the lecithin-cholesterol interaction.

δ-Tocopherol Reduces Lipid Accumulation in Niemann-Pick Type C1 and Wolman Cholesterol Storage Disorders

“…antibiotic that binds to unesterified cholesterol and is commonly used in the diagnosis of NPC1 disease (12,16,23). Treatment of NPC1 fibroblasts with either 40 M ␦-T or 80 M ␣-T significantly reduced unesterified cholesterol storage ( Fig.…”

Splice isoform and pharmacological studies reveal that sterol depletion relocalizes α-synuclein and enhances its toxicity

“…Because α-synFL foci represent lipidrich, vesicular clusters blocked in trafficking by α-synFL, we investigated whether these clusters were enriched in sterols by staining with filipin, a fluorescent probe that binds sterols (34). In control cells, filipin displayed canonical staining of the plasma membrane, which has the highest sterol content in the cell (Fig.…”

Method for Isolating Auxotrophic Mutants in Aspergillus nidulans Using N-glycosyl-polifungin

“…In 1959 Moat, Peters & Srb made the first attempts to use the antifungal effects of polyene antibiotics for selection of auxotrophic mutants in yeast. Polyene antibiotics form complexes with the sterols of cell walls (Lampen, Arnow, Borowska & Laskin, 1962;Norman et al 1972) causing considerable changes in permeability (Lampen et al 1962;Stachiewicz & Quostel, 1963;Kinsky, Luse & van Deenen, 1966). It has also been suggested that polyenes have an effect on the general conformation of the cell wall (Chuen-Chin & Feingold, 1973).…”