Characterization of the Cation and Temperature Dependence of DNA Quadruplex Hydrogen Bond Properties Using High-Resolution NMR

• Published in: Journal of the American Chemical Society 2005-10, Vol.127 (41), p.14466-14472
• Main Authors: Dingley, Andrew J, Peterson, Robert D, Grzesiek, Stephan, Feigon, Juli
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cations - chemistry; DNA - chemistry; Fundamental and applied biological sciences. Psychology; G-Quadruplexes; Guanine - chemistry; Hydrogen Bonding; Interactions. Associations; Intermolecular phenomena; Magnetic Resonance Spectroscopy - methods; Magnetic Resonance Spectroscopy - standards; Molecular biophysics; Nucleic Acid Conformation; Reference Standards; Temperature
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0540369

Variations in the hydrogen bond network of the Oxy-1.5 DNA guanine quadruplex have been monitored by trans-H-bond scalar couplings, h2 J N2N7, for Na+-, K+-, and NH4 +-bound forms over a temperature range from 5 to 55 °C. The variations in h2 J N2N7 couplings exhibit an overall trend of Na+ > K+ > NH4 + and correlate with the different cation positions and N2−H2···N7 H-bond lengths in the respective structures. A global weakening of the h2 J N2N7 couplings with increasing temperature for the three DNA quadruplex species is accompanied by a global increase of the acceptor 15N7 chemical shifts. Above 35 °C, spectral heterogeneity indicates thermal denaturation for the Na+-bound form, whereas spectral homogeneity persists up to 55 °C for the K+- and NH4 +-coordinated forms. The average relative change of the h2 J N2N7 couplings amounts to ∼0.8 × 10-3/K and is thus considerably smaller than respective values reported for nucleic acid duplexes. The significantly higher thermal stability of H-bond geometries in the DNA quadruplexes can be rationalized by their cation coordination of the G-quartets and the extensive H-bond network between the four strands. A detailed analysis of individual h2 J N2N7 couplings reveals that the 5‘ strand end, comprising base pairs G1−G9* and G4*−G1, is the most thermolabile region of the DNA quadruplex in all three cation-bound forms.