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Conformational switching for trans-membrane communication

跨膜通讯的构象转换

基本信息

批准号：
BB/I007962/1
负责人：
Jonathan Clayden
金额：
$ 77.65万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2011
资助国家：
英国
起止时间：
2011 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FI007962%2F1
关键词：
Conformational switching trans membrane communication

项目摘要

Cells are surrounded by an impermeable membrane, and one of the challenges living systems face is how to communicate information into and out of the cell through that membrane. The same challenges face scientists seeking to understand cellular behaviour using artificial cells, or vesicles, which can be used as miniature chemical reactors or transporters. Cells solve the problem either by making channels through the membrane which can conduct ions, or by rigging up a type of 'bell-pull' system, in which a tweak at the external surface of the cell leads to a change in shape of a molecule on the internal surface. This latter method has never been realised in a synthetic system, despite suitable molecules with well defined shapes, known as 'foldamers', recently becoming available to chemists. We now plan to put these foldamers to use as communicators ('transducers') of information through an artificial cell membrane. To do this we will have to develop ways of making them and of inputting and reading out information at opposite ends of the foldamer. Firstly, this will be done in solution, and then we will transfer what we discover to the membranes of vesicles. We will develop ways of studying and controlling the shape of molecules in membranes, and then build on this to construct signalling methods which allow the chemistry happening inside the vesicle to be controlled by chemical messages in the outer medium. These artificial analogues of cellular behaviour will greatly simplify the challenges presented to bioscientists wishing to understand the chemical basis of cellular communication in cells. We can also use these vesicles as miniature controllable reactors, or work out ways of making them release their contents at a controlled time or at controlled locations. Furthermore these molecules we plan to build have much in common with the 'peptaibol' class of antibiotics, and our research may give alternative, synthetic antibiotics with controllable function.

细胞被一层不可渗透的膜所包围，生命系统面临的挑战之一就是如何通过这层膜将信息传递到细胞内外。科学家们也面临着同样的挑战，他们试图利用人造细胞或囊泡来了解细胞行为，这些细胞可用作微型化学反应器或运输工具。细胞解决这个问题的方法要么是在细胞膜上制造通道，使离子能够传导，要么是装配一种“钟形拉动”系统，在这种系统中，细胞外表面的调整会导致内表面分子形状的变化。后一种方法从未在合成系统中实现，尽管最近化学家可以获得具有明确形状的合适分子，称为“折叠体”。我们现在计划将这些折叠体用作通过人工细胞膜传递信息的通讯器（“换能器”）。要做到这一点，我们将不得不发展的方法，使他们和输入和阅读信息的两端的折叠机。首先，这将在溶液中完成，然后我们将把我们发现的转移到囊泡的膜上。我们将开发研究和控制膜中分子形状的方法，然后在此基础上构建信号方法，使囊泡内部发生的化学反应受到外部介质中化学信息的控制。这些细胞行为的人工模拟物将大大简化希望了解细胞中细胞通讯化学基础的生物科学家所面临的挑战。我们还可以将这些囊泡用作微型可控反应器，或者研究出使它们在受控时间或受控位置释放其内容物的方法。此外，我们计划构建的这些分子与“peptaibol”类抗生素有很多共同之处，我们的研究可能会提供具有可控功能的替代合成抗生素。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Participation of non-aminoisobutyric acid (Aib) residues in the 3 10 helical conformation of Aib-rich foldamers: a solid state study

非氨基异丁酸 (Aib) 残基参与富含 Aib 的折叠体的 3 10 螺旋构象：固态研究

DOI：
10.1039/c4nj01547a
发表时间：
2015
期刊：
New Journal of Chemistry
影响因子：
3.3
作者：
Pike S
通讯作者：
Pike S

Diastereotopic fluorine substituents as 19F NMR probes of screw-sense preference in helical foldamers.

DOI：
10.1039/c3ob40463c
发表时间：
2013-04
期刊：
Organic & biomolecular chemistry
影响因子：
3.2
作者：
Sarah J. Pike;M. De Poli;Wojciech Zawodny;J. Raftery;S. J. Webb;J. Clayden
通讯作者：
Sarah J. Pike;M. De Poli;Wojciech Zawodny;J. Raftery;S. J. Webb;J. Clayden

Conformational Switching of a Foldamer in a Multicomponent System by pH-Filtered Selection between Competing Noncovalent Interactions.