...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Axial Hydrogen at C7 Position and Bumpy Tetracyclic Core Markedly Reduce Sterol's Affinity to Amphotericin B in Membrane
【24h】

Axial Hydrogen at C7 Position and Bumpy Tetracyclic Core Markedly Reduce Sterol's Affinity to Amphotericin B in Membrane

机译：轴向氢在C7位置和颠簸的四环核明显降低了甾醇对膜中两性霉素B的亲和力

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The interaction of amphotericin B (AmB) with fungal ergosterol (Erg) is stronger than its interaction with mammalian cholesterol (Cho), and this property of AmB as an antifungal drug is thought to be responsible for its selective toxicity toward fungi. However, the mechanism by which AmB recognizes the structural differences between sterols, particularly minor difference in the sterol alicyclic portion, is largely unknown. Thus, to investigate the mode of interaction between AmB and the sterol core, we assessed the affinity of AmB to various sterols with different alicyclic structures. Ion flux assays and UV spectral measurements clearly revealed the importance of the Delta 7-double bond of the sterol B-ring for interaction with the drug. AmB showed lower affinity for triene sterols, which have double bonds at the Delta 5, Delta 7, and Delta 9 positions. Intermolecular distance measurements by C-13{F-19} rotational echo double resonance (REDOR) revealed that the AmB macrolide ring is in closer contact with the steroid core of Erg than it is with the Cho core in the membrane. Conformational analysis suggested that an axial hydrogen atom at C7 of Delta 5-sterol (2, 6) and the protruded A-ring of Delta 5,7,9-sterol (4, 8) sterically hampered face-to-face contact between the van der Waals surface of the sterol core and the macrolide of AmB. These results further suggest that the alpha-face of sterol alicycle interacts with the flat macrolide structure of AmB.
机译：两性霉素B（AmB）与真菌麦角固醇（Erg）的相互作用比与哺乳动物胆固醇（Cho）的相互作用更强，AmB作为抗真菌药的这一特性被认为是其对真菌的选择性毒性的原因。但是，AmB识别固醇之间的结构差异，尤其是固醇脂环族部分的微小差异的机理在很大程度上尚不清楚。因此，为了研究AmB和固醇核心之间的相互作用模式，我们评估了AmB对具有不同脂环结构的各种固醇的亲和力。离子通量分析和紫外光谱测量清楚地表明，固醇B环的Delta 7-双键对于与药物相互作用的重要性。 AmB对三烯固醇的亲和力较低，后者在Delta 5，Delta 7和Delta 9位具有双键。通过C-13 {F-19}旋转回波双共振（REDOR）进行的分子间距离测量显示，AmB大环内酯环与Erg的类固醇核紧密接触，而与膜中的Cho核紧密接触。构象分析表明，δ5-甾醇（2，6）的C7处的轴向氢原子和Delta 5,7,9-甾醇（4，8）的突出A环在空间上阻碍了它们之间的面对面接触。范德华固醇核心的表面和AmB的大环内酯。这些结果进一步表明，固醇脂环族的α面与AmB的平坦大环内酯结构相互作用。

著录项

相似文献

  • 外文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号