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

四重核酸（four - plex nucleic acids, G4）由于其生物学相关性和作为生物分子工具的整体适用性，近年来成为学术界关注的焦点。与众所周知的双螺旋DNA相比，这些结构由四个鸟苷核苷酸堆叠而成，排列成四联体，与中心的一价阳离子（如Na+或K+）协调。正是这个中心反离子将允许研究人员使用核磁共振（NMR）光谱研究g4折叠和动力学的一个新的和大多被忽视的视角。到目前为止，这种尝试受到金属离子核磁共振的广泛和低灵敏度的阻碍，导致在g4研究中选择1H核磁共振作为方法。在这个项目中，我们希望在碱基核磁共振中引入一种新方法，以推动该技术的检测极限。利用激光诱导金属核的超极化和β-探测不稳定核衰变的灵敏度可提高10个数量级，从而使我们在核磁共振光谱中对g -四重体有了独特的看法。此外，这项技术将使我们能够实时接近G4的折叠和动力学控制过程，这是迄今为止难以实现传统的核磁共振技术。

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.