MOLECULAR BASIS OF ION TRANSPORT IN BIOLOGICAL MEMBRANES

跨膜离子的调节对许多人来说是至关重要的。 细胞功能。不幸的是，导致离子的机制 在分子水平上，人们对运输知之甚少。在某种程度上， 这是由于很难确定大型 固有膜离子通道。为了克服这一困难， 较小结构，可通过多个合成材料 并将研究光谱方法论。其作用机制 将研究离子通过两个简单通道的传输： 多烯大环内酯两性霉素B及其线状肽 阿拉米星。两性霉素B是一种化疗药物，也是 据报道具有抗人类免疫缺陷病毒的活性 (HV)。阿拉美辛是一种能产生电压的小肽- 模型膜中的依赖电导。除了这两个之外 渠道，一些合成肽将被调查以 确定静电相互作用在蛋白质中的作用 膜上的结合和构象。 这项工作的总体目标是阐明根本 在促进离子传导方面很重要的分子特征， 膜上的电压依赖性和蛋白质结合。通过 调查这些简单的系统，洞察操作 将获得更大的本征离子通道。新方法 为了研究蛋白质-膜相互作用，将开发 这应该具有普遍的实用性。还预计， 洞察两性霉素B的抗真菌和毒性作用 将会被获得。

The regulation of transmembrane ion critical is critical for many cell functions. Unfortunately, the mechanisms leading to ion transport are poorly understood at the molecular level. In part, this is due to the difficulty in determining the structure of large intrinsic membrane ion channels. To overcome this difficulty, small structure that are approachable with a number of synthetic and spectroscopic methodologies will be examine. The mechanisms of ion transport through two simple channels will be investigated: the polyene macrolide amphotericin B and the linear peptide alamethicin. Amphotericin B is a chemotherapy, and is also reported to have activity against the human immunodeficiency virus (HV). Alamethicin is a small peptide that produces a voltage- dependent conductance in model membranes. In addition to these two channels, a number of synthetic peptides will be investigate to determine the role that electrostatic interactions have in protein binding and conformation in membranes. The overall objectives of this work are to elucidate fundamental molecular features that are important in promoting ion conduction, voltage-dependence and protein binding in membranes. Through the investigation of these simple systems, insight into the operation of larger, intrinsic ion channels will be obtained. New approaches to investigate protein - membrane interactions will be developed that should have general utility. It is also anticipated that insight into the antifungal and toxic effects of amphotericin B will be obtained.