Non-Benzenoid Fluorophores to Enable New Imaging Modalities

非苯类荧光团可实现新的成像方式

• 批准号: EP/W036193/1
• 负责人: Simon Lewis
• 金额: $ 97.42万
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FW036193%2F1
• 关键词: Non; Benzenoid; Fluorophores; Enable; New

The development of new medicines has been central to realising the increases in life expectancy and quality of life enjoyed by modern civilization. Whereas traditional folk remedies were discovered by trial and error, modern drug development relies on having a deep understanding of the biological processes that occur for any given disease. This knowledge allows new medicines to be specifically designed with an understanding of how they actually work.In order to gain this understanding of the complex and interrelated cellular processes that can occur in either diseased or healthy cells, scientists have made extensive use of so-called "bio-imaging" techniques. The most straightforward way to acquire an image of a biological sample is to use an optical microscope of the type you might find in a biology classroom. However, It is not possible to identify the various substances that may be present in a cell just by looking at such an image. Instead, scientists make use of "fluorescent probes" - molecules that will glow a particular colour, but only in the presence of a particular substance they have been designed to detect. Using such fluorescent probes allows us to determine whether or not a substance is present, how much of it is present, where exactly within cells it occurs, and for how long it may be present. For example, fluorescent probes that allow the imaging of a protein called amyloid-beta have shown it plays a crucial role in Alzheimer's disease; other fluorescent probes have revealed the key role played by various proteins in cancer.Fluorescent probe molecules consist of a "receptor" part (whose purpose is to detect a particular substance), joined to a "fluorophore" (whose job is to emit the coloured light the microscope will detect). Currently a great number of different receptors have been developed to detect many different substances. On the other hand, when it comes to choosing a fluorophore, there are actually not that many to choose from. Specifically there are about a dozen well-known fluorophores, each with its own advantages and disadvantages. As such, there is a pressing need to discover and develop new fluorophores with different characteristics to the ones we already have, as this will allow many current limitations in bio-imaging to be overcome.We propose to develop new fluorophores based on a molecule called "azulene". The name comes from the Spanish word "azul" (="blue"), as it is highly coloured and is also fluorescent. Some azulenes occur in nature and are responsible for the blue colour of certain mushrooms and corals. The fluorescence properties of azulene will enable us to develop fluorophores that work in new ways (e.g. by emitting more than one colour of light simultaneously) and so will be able to give us valuable new information through imaging substances that have been difficult to study up to now. Longer term, it is our aspiration that these new tools we are developing will allow greater insights into disease mechanisms, hence enabling the development of new medicines for the benefit of society.

新药物的开发是实现现代文明预期寿命和生活质量提高的核心。传统的民间疗法是通过试验和错误发现的，而现代药物开发依赖于对任何特定疾病发生的生物过程的深刻理解。这些知识使新药能够在了解其实际工作原理的情况下进行专门设计。为了了解病变细胞或健康细胞中发生的复杂和相互关联的细胞过程，科学家们广泛使用了所谓的“生物成像”技术。获取生物样本图像最直接的方法是使用你可能在生物教室里找到的那种光学显微镜。然而，仅仅通过观察这样的图像是不可能识别细胞中可能存在的各种物质的。取而代之的是，科学家们使用“荧光探针”——一种分子，它会发出特定的颜色，但只有在它们被设计用来探测的特定物质存在的情况下。利用这种荧光探针，我们可以确定一种物质是否存在，存在多少，它在细胞内发生的确切位置，以及它可能存在的时间。例如，荧光探针可以成像一种叫做淀粉样蛋白的蛋白质，它在阿尔茨海默病中起着至关重要的作用；其他荧光探针揭示了各种蛋白质在癌症中所起的关键作用。荧光探针分子由一个“受体”部分（其目的是检测特定物质）和一个“荧光团”（其作用是发射显微镜将检测到的彩色光）组成。目前已经开发出许多不同的受体来检测许多不同的物质。另一方面，当谈到选择荧光团时，实际上没有那么多可供选择。具体来说，大约有十几个众所周知的荧光团，每个都有自己的优点和缺点。因此，迫切需要发现和开发具有不同特征的新荧光团，因为这将允许克服生物成像方面的许多当前限制。我们建议以一种叫做“azulene”的分子为基础开发新的荧光团。这个名字来自西班牙语单词“azul”（=“蓝色”），因为它是高度着色的，也是荧光的。一些azulene存在于自然界中，是某些蘑菇和珊瑚呈现蓝色的原因。azulene的荧光特性将使我们能够开发出以新的方式工作的荧光团（例如，同时发射多种颜色的光），因此将能够通过成像到目前为止难以研究的物质为我们提供有价值的新信息。从长远来看，我们的愿望是，我们正在开发的这些新工具将使我们能够更深入地了解疾病机制，从而能够开发造福社会的新药。