Hyperfine Resolution and Advanced Structural Analysis to Enable Next-Generation Molecular Science

超精细分辨率和高级结构分析使下一代分子科学成为可能

• 批准号: EP/V007718/1
• 负责人: Peter O'Connor
• 金额: $ 395.22万
• 依托单位: University of Warwick
• 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%2FV007718%2F1
• 关键词: Hyperfine; Resolution; Advanced; Structural; Analysis

An extremely wide range of molecular species are present in everyday materials such as petroleum, biodegradation materials such as lignin (a precursor to some biofuels), synthetic polymers and plastics, and of course, living organisms have many different types of small molecules (hormones, cell-wall lipids, amino acids, sugars) as well as many large molecules like proteins and DNA. For scientists to be able to use these molecules for new technologies, all of these molecules require detailed molecular structure determination, and mass spectrometry is a key tool in the toolbox of analysis techniques. The Fourier transform ion cyclotron resonance (FTICR) mass spectrometer is a particularly advanced type of mass spectrometer widely used for ultra-high resolution, mass accuracy, and experiments requiring detailed structural analysis of molecules. Furthermore, the FTICR mass spectrometer is the most versatile type of mass spectrometer with many different ways to observe and characterise the structural detail of molecules. The proposed instrument will also include the ability to fragment ions in different ways thus providing the ability to distinguish molecules which differ in their molecular structure, but not their mass (i.e. isomers - which are extraordinarily common in biomolecules, for example cis- versus trans- fats or different types of sugars). This new instrument will also add substantially improved instrument control and data analysis software and electronics which will also improve data quality and acquisition speed by about a factor of 2-3.Additionally, in collaboration with the only commercial manufacturer of these instruments, Bruker, we will develop several new technologies that will improve our ability to analyse complex mixtures of molecules. This collaboration with Bruker will enhance the impact of this research by providing a direct route to market for these developments (with appropriate intellectual property protection and licensing), which will allow these developments to be rapidly rolled-out to future and existing FTICR users via Bruker's established commercial distribution routes. This new instrument will substantially expand our capability to study chemistry and biology, as above, but it will also greatly improve our ability to study small drug molecules, whether natural or synthetic, in their natural, active biological environment. For example, the 'stiffening' of proteins with age is partially due to sugar-related modifications called glycation, which accumulate over time on collagen in the joints, and is particularly common in diabetics which is measured quarterly with the HbA1c clinical assay. This instrument will allow improved study of the biochemical mechanism of formation and positional dependence of such modifications so that we can help inform the medical community on alternatives to enhance healthy living in an aging population. The instrument will also improve our ability to study biofuel production and potential downstream environmental impacts - thus providing the ability to design production to minimize the negative impacts. This instrument will be set up as a sustainably funded national collaborative mass spectrometry resource, overseen by a Strategic Advisory Board of experienced academics and industrialists and will be made available through various mechanisms to the wider scientific community in science and industry. Projects will be prioritized based on 1) scientific excellence, 2) EPSRC remit, 3) impact, 4) early career researcher access, and 5) all other projects. The new instrument will be made available for these prioritized collaborative or user research projects for at least 250 days per year.

在日常材料中存在着非常广泛的分子种类，如石油，生物降解材料，如木质素（一些生物燃料的前体），合成聚合物和塑料，当然，生物体有许多不同类型的小分子（激素，细胞壁脂质，氨基酸，糖）以及许多大分子，如蛋白质和DNA。为了使科学家能够将这些分子用于新技术，所有这些分子都需要详细的分子结构测定，而质谱是分析技术工具箱中的关键工具。傅里叶变换离子回旋共振（FTICR）质谱仪是一种特别先进的质谱仪，广泛用于超高分辨率，质量精度和需要详细分子结构分析的实验。此外，FTICR质谱仪是最通用的质谱仪类型，具有许多不同的方法来观察和分析分子的结构细节。所提出的仪器还将包括以不同方式使离子碎片化的能力，从而提供区分分子结构不同但质量不同的分子（即异构体-其在生物分子中非常常见，例如顺式脂肪与反式脂肪或不同类型的糖）的能力。这款新仪器还将大幅改进仪器控制和数据分析软件以及电子设备，从而将数据质量和采集速度提高约2- 3倍。此外，我们还将与这些仪器的唯一商业制造商布鲁克公司合作，开发几项新技术，以提高我们分析复杂分子混合物的能力。与布鲁克的合作将为这些开发提供直接的市场途径（通过适当的知识产权保护和许可），从而增强这项研究的影响力，这将使这些开发能够通过布鲁克已建立的商业分销途径迅速推广到未来和现有的FTICR用户。这种新仪器将大大扩展我们研究化学和生物学的能力，如上所述，但它也将大大提高我们研究小药物分子的能力，无论是天然的还是合成的，在它们的自然，活性生物环境中。例如，随着年龄的增长，蛋白质的“硬化”部分是由于糖相关的修饰，称为糖化，随着时间的推移，它会在关节中的胶原蛋白上积累，并且在糖尿病患者中特别常见，这是每季度用HbA 1c临床检测来测量的。该仪器将允许改进对这种修饰的形成和位置依赖性的生化机制的研究，以便我们可以帮助告知医学界关于在老龄化人口中增强健康生活的替代方案。该工具还将提高我们研究生物燃料生产和潜在下游环境影响的能力，从而提供设计生产以尽量减少负面影响的能力。该仪器将作为一个可持续供资的国家合作质谱资源，由经验丰富的学术界和工业界的战略咨询委员会监督，并将通过各种机制提供给更广泛的科学界和工业界。项目将根据1）科学卓越，2）EPSRC职权范围，3）影响，4）早期职业研究人员访问，以及5）所有其他项目进行优先排序。新工具将每年至少为这些优先合作或用户研究项目提供250天。

项目成果

Facile protein conjugation of platinum for light-activated cytotoxic payload release.

• DOI: 10.1039/d1cc02722k
• 发表时间: 2021-08-03
• 期刊: Chemical communications (Cambridge, England)
• 作者: Imberti C;Lermyte F;Friar EP;O'Connor PB;Sadler PJ
• 通讯作者: Sadler PJ

Characterizing lignins from various sources and treatment processes after optimized sample preparation techniques and analysis via ESI-HRMS and custom mass defect software tools.

• DOI: 10.1007/s00216-023-04942-x
• 发表时间: 2023-11
• 期刊: ANALYTICAL AND BIOANALYTICAL CHEMISTRY
• 影响因子: 4.3
• 作者: Letourneau, Dane R.;Marzullo, Bryan P.;Alexandridou, Anastasia;Barrow, Mark P.;O'Connor, Peter B.;Volmer, Dietrich A.
• 通讯作者: Volmer, Dietrich A.

Investigating the Influence of n-Heptane versus n-Nonane upon the Extraction of Asphaltenes.

• DOI: 10.1021/acs.energyfuels.2c01168
• 发表时间: 2022-08-18
• 期刊: ENERGY & FUELS
• 影响因子: 5.3
• 作者: Alostad, Latifa K.;Lozano, Diana Catalina Palacio;Gannon, Benedict;Downham, Rory P.;Jones, Hugh E.;Barrow, Mark P.
• 通讯作者: Barrow, Mark P.

In Silico Demonstration of Two-Dimensional Mass Spectrometry Using Spatially Dependent Fragmentation.

• DOI: 10.1021/jasms.2c00241
• 发表时间: 2023-03-01
• 期刊: JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
• 影响因子: 3.2
• 作者: Littlejohn, Callan;Li, Meng;O'Connor, Peter B.
• 通讯作者: O'Connor, Peter B.

Stochasticity of poly(2-oxazoline) oligomer hydrolysis determined by tandem mass spectrometry.

• DOI: 10.1039/d2py00437b
• 发表时间: 2022-07-19
• 期刊: POLYMER CHEMISTRY
• 影响因子: 4.6
• 作者: Morgan, Tomos E.;Floyd, Thomas G.;Marzullo, Bryan P.;Wootton, Christopher A.;Barrow, Mark P.;Bristow, Anthony W. T.;Perrier, Sebastien;O'Connor, Peter B.
• 通讯作者: O'Connor, Peter B.