Stimulated Raman Spectroscopy: A new tool for profiling intracellular catalysis

受激拉曼光谱：分析细胞内催化作用的新工具

• 批准号: BB/N021614/1
• 负责人: Alison Hulme
• 金额: $ 13.77万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN021614%2F1
• 关键词: Stimulated; Raman; Spectroscopy; new; tool

Understanding how fast small molecules (such as drugs) or biomolecules (such as DNA) react inside cells is crucial to the development of new medicines and the design of successful industrial processes which rely on bio-transformations. And yet at the moment there are no tools which can give both the location of a biomolecule and its rate of reaction in live cells simply relying on the inherent properties of that molecule. Current strategies either require the cell or tissue under examination to be fixed (as for histological slides) so that the concentrations of compounds can be mapped by mass spectrometry (thus not applicable for examining reactions in living cells), or rely on the incorporation of isotopes to allow detection of the molecule under study by its nuclear magnetic resonance (a technique which does not allow the position of reacting molecule within the cell to be accurately determined).A new technique, called stimulated Raman spectroscopy (SRS), allows the vibrational properties of a molecule to be measured in a way that is:* quantitative - allowing accurate measurement of local concentrations;* spatially resolved - allowing molecules to be mapped inside cells;* chemically discriminating - allowing different types of molecules to be imaged at the same time;* and uses non-destructive optical light for detection - meaning that the studies could eventually be transferred to fibre optic technologies to be used in patients.We propose to use SRS to study the rate of one particular reaction inside cells so that we can demonstrate that it is possible to do this both in the presence of all of the other signals from the cell, and in a way that allows us to show exactly where the reacting molecules are inside a cell.

了解小分子（例如药物）或生物分子（例如 DNA）在细胞内反应的速度对于新药的开发和依赖生物转化的成功工业流程的设计至关重要。然而，目前还没有工具可以仅依靠该分子的固有特性来确定生物分子的位置及其在活细胞中的反应速率。目前的策略要么需要固定所检查的细胞或组织（如组织学切片），以便可以通过质谱法绘制化合物的浓度图（因此不适用于检查活细胞中的反应），要么依靠同位素的掺入来允许通过核磁共振检测所研究的分子（这种技术不允许准确确定细胞内反应分子的位置）。一种新技术，称为 受激拉曼光谱 (SRS) 允许以以下方式测量分子的振动特性：* 定量 - 允许精确测量局部浓度；* 空间分辨 - 允许在细胞内绘制分子图；* 化学区分 - 允许同时对不同类型的分子成像；* 并使用非破坏性光学光进行检测 - 这意味着 研究最终可以转移到用于患者的光纤技术。我们建议使用 SRS 来研究细胞内某一特定反应的速率，以便我们能够证明，在存在来自细胞的所有其他信号的情况下，并且以一种允许我们准确显示反应分子在细胞内的位置的方式来做到这一点是可能的。

项目成果

Kinetic analysis of bioorthogonal reaction mechanisms using Raman microscopy.

使用拉曼显微镜对生物正交反应机制进行动力学分析。

• DOI: 10.1039/c9fd00057g
• 发表时间: 2019
• 期刊: Faraday discussions
• 影响因子: 3.4
• 作者: Tipping WJ

Imaging drug uptake by bioorthogonal stimulated Raman scattering microscopy.

• DOI: 10.1039/c7sc01837a
• 发表时间: 2017-08-01
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Tipping WJ;Lee M;Serrels A;Brunton VG;Hulme AN
• 通讯作者: Hulme AN

Stretching the Bisalkyne Raman Spectral Palette Reveals a New Electrophilic Covalent Motif.

拉伸双炔拉曼光谱调色板揭示了一种新的亲电共价基序。

• DOI: 10.1002/chem.202300953
• 发表时间: 2023
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
• 作者: Ravindra MP