Electron-vibration-vibration 2DIR spectroscopy to study the folding of G-quadruplex DNA structures A. Larasati Soenarjo 1 , Zhihao Lan 2 , Paul M. Donaldson 3 , Igor V. Sazanovich 3 , Yee San Chan 1 , Magnus Ringholm 4 , Ajay Jha 2,5 , David R. Klug 1 1 Department of Chemistry, Imperial College London, White City Campus, UK, 2 Rosalind Franklin Institute, STFC Rutherford Appleton Laboratory, Harwell Campus, UK, 3 Central Laser Facility, Research Complex at Harwell, STFC Rutherford Appleton Laboratory, UK, 4 Hylleraas Centre for Quantum Molecular Sciences, Department of Chemistry, UiT The Arctic University of Norway, Norway, 5 Department of Pharmacology, University of Oxford, UK G-quadruplexes (G4) are non-canonical DNA structures which consist of vertically stacked, planar guanine quartets coordinated to cations. 1 Small molecule binders that stabilize the G4 structure have been shown to modulate the expression of genes which contain G4 forming sequences in the promoter region. 2 In this work, we use Electron-Vibration-Vibration two-dimensional infrared (EVV 2D IR) spectroscopy to study the folding of the G4 structure induced by the increase in cation concentration. EVV 2D IR spectroscopy is a hybrid IR-Raman four-wave mixing spectroscopy that utilizes two mid-IR pulses and a near-IR/visible pulse to measure vibrational coupling. 3,4 We observe ~ 100 cross-peaks/couplings and three phenomena which we attribute to the folding of the G4 structure. This includes frequency shifts, changes in intensity and the appearance of new cross-peaks/ couplings. DFT calculations have been used to give insight into the structural changes that give rise to these phenomena. References 1. Spiegel, J., Adhikari, S., &; Balasubramanian, S. (2020). The Structure and Function of DNA G-Quadruplexes. Trends in Chemistry , 2 (2), 123–136. https://doi.org/https://doi.org/10.1016/j.trechm.2019.07.002 2. Siddiqui-Jain, A., Grand, C. L., Bearss, D. J., &; Hurley, L. H. (2002). Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c- MYC transcription. Proceedings of the National Academy of Sciences , 99 (18), 11593–11598. https://doi.org/10.1073/pnas.182256799 3. Sowley, H., Liu, Z., Davies, J., Peach, R., Guo, R., Sim, S., Long, F., Holdgate, G., Willison, K., Zhuang, W., &; Klug, D. R. (2019). Detection of Drug Binding to a Target Protein Using EVV 2DIR Spectroscopy. Journal of Physical Chemistry B , 123 (17), 3598–3606. https://doi.org/10.1021/acs.jpcb.9b00501 4. Donaldson, P. M. (2020). Photon echoes and two dimensional spectra of the amide I band of proteins measured by femtosecond IR-Raman spectroscopy. Chemical Science , 11 (33), 8862–8874. https://doi.org/10.1039/d0sc02978e
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