High-performance NMR combining β-detection and hyperpolarization for G-Quadruplex structure and dynamics studies

高性能 NMR 结合 β 检测和超极化，用于 G-四链体结构和动力学研究

• 批准号: 441102113
• 负责人: Dr. Beatrice Karg
• 金额: --
• 依托单位: Département de Physique Nucléaire et Corpusculaire (DPNC)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/441102113?language=en
• 关键词: performance; NMR; combining; detection; hyperpolarization

Due to their biological relevance and overall applicability as biomolecular tools, quadruplex nucleic acids (G4) have reached the academic spotlight in recent years. Compared to their well-known counterpart, double-helical DNA, these structures are comprised of stacks of four Guanosine-nucleotides arranged in a tetrad which are coordinated to a central monovalent cation such as Na+ or K+. It is this central counter-ion which will allow researchers a new and mostly neglected perspective on G4-folding and dynamics using Nuclear Magnetic Resonance (NMR) spectroscopy. Up until now such attempts are hampered by broad and low sensitivity of metal-ion NMR resonances resulting in 1H NMR as the method of choice in G4-studies. Within this project, we want to introduce a new approach in alkali-based NMR to push the technique’s detection limits. Using laser-induced hyperpolarization of metal nuclei and β-detection of nuclear decay of unstable nuclei sensitivity enhancements of up to 10 orders of magnitude can be achieved, thus enabling us a unique view on G-quadruplexes in NMR-spectroscopy. Furthermore this technique will allow us a real-time approach towards the folding of G4 and the dynamics governing the process which is so far difficult to achieve with conventional NMR techniques.

四链体核酸（G4）由于其生物学相关性和作为生物分子工具的全面适用性，近年来已成为学术界的热点。与它们众所周知的对应物双螺旋DNA相比，这些结构由排列在四分体中的四个鸟苷核苷酸的堆叠组成，所述四分体与中心单价阳离子如Na+或K+配位。正是这种中心反离子将使研究人员能够使用核磁共振（NMR）光谱对G4折叠和动力学进行新的且大多被忽视的视角。到目前为止，这种尝试受到金属离子NMR共振的宽和低灵敏度的阻碍，导致1H NMR作为G4研究中的选择方法。在这个项目中，我们希望引入一种基于碱的NMR的新方法，以提高该技术的检测极限。使用激光诱导的金属核超极化和不稳定核的核衰变的β-检测，可以实现高达10个数量级的灵敏度增强，从而使我们能够在NMR光谱中对G-四链体有独特的看法。此外，这种技术将使我们能够实时的方法对G4的折叠和动态管理的过程，这是迄今为止难以实现与传统的NMR技术。

项目成果

Time-Dependent Hydrogen Bond Network Formation in Glycerol-Based Deep Eutectic Solvents.

• DOI: 10.1002/cphc.202100806
• 发表时间: 2022-04
• 期刊: Chemphyschem : a European journal of chemical physics and physical chemistry
• 作者: K. Dziubinska-Kühn;Marion Pupier;J. Matysik;Jasmine Viger‐Gravel;B. Karg;M. Kowalska

Simulations of electric field gradient fluctuations and dynamics around sodium ions in ionic liquids.

离子液体中钠离子周围电场梯度波动和动力学的模拟

• DOI: 10.1063/5.0126693
• 发表时间: 2022
• 期刊: The Journal of chemical physics
• 作者: Gimbal-Zofka;Dziubinska-Kühn;Kowalska;Wesolowski;Rumble
• 通讯作者: Rumble