Guanine-rich nucleic acid sequences form tetrameric complexes in the presence of metal cations termed G-quadruplexes or G-quads. The formation and stability of G-quads depends on the presence of alkali metal cations (K+&gt;Na+&gt;Li+). G-quads can also form higher-order structures, such as aggregates, that have been implicated in gene regulation as well as diseases such as Amyotrophic Lateral Sclerosis (ALS) and Frontal Temporal Dementia (FTD). Using infrared spectroscopy, we have established spectral signatures of model G-quads by observing frequency and lineshape shifts under varying salt conditions. Because its sensitivity to vibrational coupling, local electrostatics and solvent exposure, infrared spectroscopy is able to detect the formation of G-quads. We focus on the in-plane vibrational modes of guanine between 1500 cm-1 and 1750 cm-1, which are sensitive to the K+ binding and Hoogsteen base pairing in G-quads. Upon investigating different lengths of repeat sequences, the resulting blue shift trend in the FTIR spectra indicate a preference for three to four layers in the most stable G-quad structures, which corresponds to typical repeat lengths observed in naturally occurring G-quads in non-aggregating structures. Our results point to possible entropic effects in the stability of G-quads which will be examined by spectroscopic and calorimetric methods. Current and future studies using two dimensional infrared (2D IR) spectroscopy will further our understanding of the structural changes associated with the introduction of disorder in G-quads composed both of DNA and RNA.

Infrared spectroscopy reveals a base stacking limit in DNA G-quadruplexes

253rd National Meeting (2017)

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