A bottom-up approach to the rational design of new bioluminescence emitters

新型生物发光发射器合理设计的自下而上方法

• 批准号: EP/T011637/1
• 负责人: Helen Fielding
• 金额: $ 175.05万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FT011637%2F1
• 关键词: bottom; up; approach; rational; design

This research will improve our molecular level understanding of bioluminescence for the rational design of new near-infrared emitters for advanced bioluminescence imaging applications. Bioluminescence is the emission of light by living organisms. It is one of Nature's most spectacular phenomena and continues to challenge those who try to understand it. The yellow-green glow of fireflies is one of the brightest and most beautiful examples of bioluminescence. The biochemical process involves the catalytic oxidation of a small molecule (luciferin) by an enzyme (luciferase) to form an electronically excited oxyluciferin that subsequently relaxes to its ground state by emitting light. Harnessing bioluminescence for imaging applications has revolutionised the biosciences. Bioluminescence imaging is now a standard tool for visualising molecular and cellular processes in vivo. However, more advanced applications are limited by reduced sensitivity in deep tissue arising from the absorption of visible light by blood and tissue. New far-red and near-infrared bioluminescence systems for enhanced sensitivity and resolution in deep tissue have recently become available; however, they are limited by their brightness and narrow spectral range. There is a pressing need for bright, multicolor, far-red and near-infrared emitters. To date, modifications to bioluminescent systems have relied on incremental changes and small library-based approaches. We propose to use a fundamentally new, bottom-up approach. We will use state-of-the-art spectroscopy measurements and quantum chemistry calculations to learn which electronic states and molecular motions of far-red and near-infrared luciferins are important in the competing non-radiative relaxation pathways that reduce the brightness of bioluminescence and we will learn how luciferase enzymes tune the bioluminescence wavelength. We will then use this information to design new, bright bioluminescent emitters for multicolour, far-red and near-infrared bioluminescence imaging.

这项研究将提高我们对生物发光的分子水平的理解，用于用于晚期生物发光成像应用的新近红外发射器的合理设计。生物发光是活生物体发射的光。它是自然界最壮观的现象之一，并继续挑战那些试图理解它的人。萤火虫的黄绿色光芒是生物发光的最亮，最美丽的例子之一。生化过程涉及通过酶（荧光素酶）催化小分子（荧光素）的催化氧化，以形成电子激发的羟基糖蛋白，随后通过发光将其放松至其基态。利用生物发光用于成像应用已彻底改变了生物科学。现在，生物发光成像是在体内可视化分子和细胞过程的标准工具。但是，更先进的应用受到深层组织的敏感性降低而受到限制，这是由于血液和组织吸收可见光。最近已获得了新的远红和近红外生物发光系统，以增强深层组织的灵敏度和分辨率。但是，它们受到亮度和光谱范围狭窄的限制。迫切需要明亮，多色，远红和近红外发射器。迄今为止，对生物发光系统的修改依赖于增量变化和基于图书馆的小方法。我们建议采用一种根本新的自下而上的方法。我们将使用最先进的光谱测量和量子化学计算来了解远红色和近红外荧光素的电子状态和分子运动在竞争性的非辐射性放松途径中很重要，从而降低了生物发光和生物发光的亮度我们将学习荧光素酶如何调整生物发光波长。然后，我们将使用此信息来设计新的，明亮的生物发光发射器，用于多色，远红和近红外生物发光成像。

项目成果

Wavelength dependent mechanism of phenolate photooxidation in aqueous solution.

• DOI: 10.1039/d3sc00016h
• 发表时间: 2023-03-22
• 期刊: Chemical science
• 影响因子: 8.4

Accurate Vertical Ionization Energy of Water and Retrieval of True Ultraviolet Photoelectron Spectra of Aqueous Solutions.

• DOI: 10.1021/acs.jpclett.2c01768
• 发表时间: 2022-08-04
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY LETTERS
• 影响因子: 5.7
• 作者: Scholz, Michael S.;Fortune, William G.;Tau, Omri;Fielding, Helen H.
• 通讯作者: Fielding, Helen H.

UV Photoelectron Spectroscopy of Aqueous Solutions.

• DOI: 10.1021/acs.accounts.2c00523
• 发表时间: 2022-12-20
• 期刊: ACCOUNTS OF CHEMICAL RESEARCH
• 影响因子: 18.3
• 作者: Fortune, William G.;Scholz, Michael S.;Fielding, Helen H.
• 通讯作者: Fielding, Helen H.