Molecular Structure of Amphotericin B Channels

两性霉素 B 通道的分子结构

• 批准号: 9204564
• 负责人: Scott Hartsel
• 金额: $ 8.83万
• 依托单位: University of Wisconsin-Eau Claire
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-11-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9204564&HistoricalAwards=false
• 关键词: Molecular; Structure; Amphotericin; Channels

One of the classic model compounds for membrane ion channel permeation is Amphotericin B, although the structure of the channel is still unknown. This polyene macrolide is thought to form ion permeable pores in lipid membranes by organizing into a barrel stave like arrangement of molecules with the polar polyol region in the middle. However, the size and nature of the channels seem to vary depending upon which sterol, ergosterol or cholesterol, is present in the phospholipid membrane. The supramolecular structure of such channels may be revealed by studying its ion permeation properties, especially the selectivity sequence of related ions (e.g. the alkali metal series). The three basic goals for this research are: 1)Obtain complete Group IA and IIA metal cation and halide selectivity sequences for Amphotericin channels in different phospholipid and sterol membrane environments, 2) Determine the temperature dependence, aggregation state and molecularity of channel formation in these environments, 3) Using these data in conjunction with electrostatic molecular modeling software, design consistent models for Amphotericin channel structures. %%% Biological membrane ion channels play a central role in many processes from neurotransmission to cystic fibrosis. This research should advance on knowledge of Amphotericin channels and ion channels in general.

膜离子通道的经典模型化合物之一 两性霉素B，尽管通道的结构 仍然未知。 这种多烯大环内酯被认为可以形成离子 通过组织成桶而在脂膜中形成可渗透孔 分子的板条状排列，其中极性多元醇区域在 中间 然而，渠道的规模和性质似乎 不同的甾醇，麦角甾醇或胆固醇， 存在于磷脂膜中。 超分子结构 通过研究其离子渗透， 性质，特别是相关离子的选择性序列 (e.g.碱金属系列）。 这三个基本目标 研究内容是：1）获得完整的IA族和IIA族金属阳离子， 不同细胞中两性霉素通道的卤化物选择性序列 磷脂和甾醇膜环境，2）确定 温度依赖性、聚集态和分子结构 在这些环境中形成通道，3）使用这些数据， 结合静电分子模拟软件，设计 两性霉素通道结构的一致模型。 %%% 生物膜离子通道在许多生物学过程中起着核心作用。 从神经传递到囊性纤维化。 本研究 两性霉素通道和离子知识应进一步发展 渠道一般。