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

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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.