The design synthesis and biological application of tools to enable the wavelength-dependent control of receptor activation and inhibition.

工具的设计合成和生物学应用，能够实现受体激活和抑制的波长依赖性控制。

• 批准号: BB/E005756/1
• 负责人: Stuart Conway
• 金额: $ 10.75万
• 依托单位: University of St Andrews
• 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=BB%2FE005756%2F1
• 关键词: design; synthesis; biological; application; tools

We are interested in making chemicals that will help us to understand how certain biological processes work. We are particularly interested in the proteins that the active component of cannabis interacts with the so called 'cannabinoid receptors'. We are also interested in the proteins that the 'hot' component of chilli peppers acts on, which is called TRPV1. These proteins have many interesting biological effects that we would like to understand in more detail. One of the problems with studying these proteins is that they are located in the cell membrane and so it is difficult to investigate them with out disturbing their environment. Another problem is controlling when and where we turn the proteins 'on'. If we simply apply chemicals to activate these proteins then it will not always be possible to control where the chemicals go and hence we may activate some proteins that we don't want to interfere with. One way of solving these problems is by making chemicals that are not biologically active until they are illuminated. This is good as light does not disrupt the cell's environment too much. By using a very small and accurate source of light (a laser) we can control when and where the chemical is released in the cell very accurately. The technology to do this already exists, but so far no one has been able to release two different chemicals (say one that turns the protein 'on' and another one that turns it 'off') in the cell at different times. We aim to do this by altering the wavelength of light that is required to activate each chemical. Light of different colours has different wavelengths, so you can think of us using one colour of light to turn the protein 'on' and another to turn it 'off'. This technology will be very powerful, as it will give us a level of control over activation of the protein that is not currently possible.

我们对制造化学品感兴趣，这将有助于我们了解某些生物过程是如何工作的。我们对大麻的活性成分与所谓的“大麻素受体”相互作用的蛋白质特别感兴趣。我们还对辣椒中“热”成分作用的蛋白质感兴趣，这种蛋白质被称为TRPV1。这些蛋白质有许多有趣的生物学效应，我们希望更详细地了解。研究这些蛋白质的问题之一是它们位于细胞膜上，因此很难在不干扰其环境的情况下对其进行研究。另一个问题是控制我们何时何地打开蛋白质。如果我们只是简单地应用化学物质来激活这些蛋白质，那么并不总是能够控制化学物质的去向，因此我们可能会激活一些我们不想干扰的蛋白质。解决这些问题的一种方法是制造在被光照之前没有生物活性的化学物质。这是好的，因为光不会过多地破坏细胞的环境。通过使用非常小和精确的光源（激光），我们可以非常精确地控制化学物质在细胞中释放的时间和位置。做到这一点的技术已经存在，但到目前为止，还没有人能够在不同的时间在细胞中释放两种不同的化学物质（比如一种使蛋白质“打开”，另一种使蛋白质“关闭”）。我们的目标是通过改变激活每种化学物质所需的光的波长来做到这一点。不同颜色的光有不同的波长，所以你可以想象我们使用一种颜色的光来“打开”蛋白质，另一种颜色的光来“关闭”蛋白质。这项技术将非常强大，因为它将使我们能够控制蛋白质的激活，这是目前不可能的。

项目成果

Synthesis, photolysis studies and in vitro photorelease of caged TRPV1 agonists and antagonists.

笼养 TRPV1 激动剂和拮抗剂的合成、光解研究和体外光释放。

• DOI: 10.1039/b914981c
• 发表时间: 2009
• 期刊: Organic & biomolecular chemistry
• 影响因子: 3.2
• 作者: Van Ryssen MP