Interaction of the polyene antibiotic etruscomycin with large unilamellar lipid vesicles: binding and proton permeability inducement.
Interaction of the polyene antibiotic etruscomycin with large unilamellar lipid vesicles: binding and proton permeability inducement.
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多烯抗生素伊特鲁可霉素与大单层脂质囊泡的相互作用：结合和质子渗透性诱导。
DOI：
10.1016/0005-2736(85)90216-0
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
J. Bolard
中科院分区：
文献类型：
--
作者：
E. Capuozzo;J. Bolard
研究了多烯抗生素伊曲霉素对大单层脂质囊泡通透性的影响。只有在膜中存在甾醇时，蛋黄磷脂酰胆碱（EPC）囊泡才会发生质子渗漏；泄漏的程度是有限的。较高的伊霉素/脂质比值(R)是必需的（R = 0.1）。较高比例的甾醇增加了渗透性，麦角甾醇的渗透性比胆固醇稍强。双棕榈酰磷脂酰胆碱（DPPC）囊泡对渗透性诱导更敏感，即使在双分子层中没有甾醇的情况下（诱导率为0.0.06）。通过圆二色性、荧光和31 - P-NMR检测了伊曲霉素与囊泡的相互作用。在诱导通透性的抗生素浓度范围内，EPC囊泡的R>为0.1，DPPC囊泡的R>为0.06，etruscomycin表现出独立于甾醇存在的典型圆二色光谱。在相同条件下，31个P-NMR和荧光研究表明囊泡双层被破坏或融合。在较低的伊曲霉素浓度下（R< 0.03），伊曲霉素的圆二色性光谱不同，表明其与含麦角甾醇的膜的相互作用不同于与含胆固醇的膜的相互作用。从荧光强度的增加与这种相互作用的相关性以及交换实验中可以推断，在低抗生素/脂质比下，伊曲霉素与含麦角甾醇的囊泡的结合比与含胆固醇的囊泡的结合更强。这些结果及其与其他多烯抗生素的比较表明，在低R时，特鲁霉素与两性霉素而非filipin更倾向于与含麦角甾醇的囊泡结合。在较高的R下，也就是在诱导磁导率的条件下，选择性是不同的。相应的机制似乎不涉及形成外霉素-甾醇通道，因为复合物的疏水链太短而无法形成通道。
The effect of the polyene antibiotic etruscomycin on the permeability of large unilamellar lipid vesicles was investigated. Proton leakage was induced in egg-yolk phosphatidylcholine (EPC) vesicles only when sterol was present in the membrane; the extent of leakage was limited. High etruscomycin/lipid ratios (R) were necessary (R> 0.1). Higher percentages of sterol increased the permeability, slightly more strongly for ergosterol than for cholesterol. Dipalmitoylphosphatidylcholine (DPPC) vesicles were more sensitive to permeability inducement, even in the absence of sterol in the bilayer (inducement for R> 0.06). The interactions of etruscomycin with the vesicles were examined by circular dichroism, fluorescence and 31 P-NMR. In the range of antibiotic concentration where permeability was induced, R> 0.1 for EPC vesicles, R> 0.06 for DPPC vesicles, etruscomycin exhibited characteristic circular dichroism spectra independent of the presence of sterol. Under the same conditions, 31 P-NMR and fluorescence studies indicated a destruction or a fusion of the vesicle bilayer. At lower etruscomycin concentrations (R< 0.03), the etruscomycin circular dichroism spectra were different, indicating that the interaction with membranes containing ergosterol differed from that with membranes containing cholesterol. From correlating the increase in fluorescence intensity with this interaction, as well as from exchange experiments, it was inferred that etruscomycin at a low antibiotic/lipid ratio is more strongly bound to ergosterol-containing vesicles than to cholesterol-containing vesicles. These results and their comparison with the results obtained with other polyene antibiotics indicate that at low R etruscomycin resembles amphotericin rather than filipin in its preferential binding to ergosterol-containing vesicles. At higher R, that is in conditions where permeability is induced, the selectivity is different. The corresponding mechanism seems not to involve the formation of an etruscomycin-sterol channel, since the hydrophobic chain of the complex would be too short to form a channel.
可用于治疗全身真菌感染的抗真菌剂。
DOI：
10.1146/annurev.pa.23.040183.001511
发表时间：
1983
影响因子：
12.5
作者：
Medoff,G;Brajtburg,J;Kobayashi,GS;Bolard,J
通讯作者：
Bolard,J
多烯抗生素与磷脂酰胆碱/甾醇囊泡复合物的解离动力学和平衡结合特性。
影响因子：
2.9
作者：
Witzke,NM;Bittman,R
通讯作者：
Bittman,R
DOI：
10.1016/0005-2736(80)90558-1
发表时间：
1980-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
SZOKA, F;OLSON, F;PAPAHADJOPOULOS, D
通讯作者：
PAPAHADJOPOULOS, D