SUPRAMOLECULAR APPROACHES TO MEMBRANE CO-TRANSPORT OF HCl

HCl 膜共转运的超分子方法

• 批准号: EP/D03549X/1
• 负责人: Philip Alan Gale
• 金额: $ 26.6万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FD03549X%2F1
• 关键词: SUPRAMOLECULAR; APPROACHES; MEMBRANE; CO; TRANSPORT

In cells there are compartments (endosomes) containing higher concentrations of HCl than are found in the rest of the cell. These comparments have walls consisting of lipid bilayer membranes - which have an oily or lipophilic interior that the HCl cannot cross easily as HCl consists of two charged species (H+ and Cl-) which prefer not to be in a lipophilic environment. The aim of this project is to design smart molecules which can recognise HCl and carry it across the lipid bilayer. The molecules are designed to bind the HCl and wrap it up in an organic coat which is soluble in the membrane. Because there is a difference in HCl concentration across the membrane the molecules will act to equalise the concentration of HCl by diffusing and releasing the HCl on the low concentration side and then diffusing back to the high concentration side to bind another HCl. We will design and test molecules to do this in model systems first and then in collaboration with a group in the US will test them in vesicles and in cells. By transporting the HCl we disrupt chemical potentials in the cell. This might be useful if we wish to kill the cell if it is a cancer cell. Additionally, the transport of HCl can disturb the function of important proteins in the cell membrane by changing the pH (ATPase uncoupler activity). This may lead to other interesting biological activity. The project is a collaboration between the Gale group in Southampton (design and synthesis of receptors and binding studies) and the Smith group at Notre Dame (vesicle and cell studies). The PDRA will visit Notre Dame twice during the course of the project and will transfer the knowledge gained in membrane studies back to Southampton.

在细胞中，有室室（核内体）含有比细胞其他部分更高浓度的盐酸。这些小室的壁由脂质双层膜组成，脂质双层膜具有油性或亲脂性的内部，HCl不能轻易穿过，因为HCl由两种带电物质（H+和Cl-）组成，它们不喜欢在亲脂性环境中。这个项目的目的是设计智能分子，可以识别HCl并携带它穿过脂质双分子层。这些分子被设计成与HCl结合，并将其包裹在一层可溶于膜的有机涂层中。因为膜上的HCl浓度不同分子会通过扩散和释放低浓度侧的HCl然后扩散回高浓度侧结合另一个HCl来平衡HCl的浓度。我们将首先在模型系统中设计和测试分子，然后与美国的一个小组合作，在囊泡和细胞中进行测试。通过运输HCl，我们破坏了细胞内的化学势。如果我们想杀死癌细胞，这可能很有用。此外，HCl的转运可以通过改变pH （atp酶解偶联剂活性）扰乱细胞膜上重要蛋白质的功能。这可能会导致其他有趣的生物活动。该项目是南安普顿的Gale小组（设计和合成受体和结合研究）和圣母大学的Smith小组（囊泡和细胞研究）之间的合作。PDRA将在项目过程中两次访问巴黎圣母院，并将在膜研究中获得的知识转移回南安普顿。