Sugar-Edge Interactions in a DNA-RNA G-Quadruplex: Evidence of Sequential C-H•••O Hydrogen Bonds Contributing to RNA Quadruplex Folding

DNA G-quadruplexes were systematically modified by single riboguanosine (rG) substitutions at anti-dG positions. Circular dichroism and NMR experiments confirmed the conservation of the native quadruplex topology for most of the DNA-RNA hybrid structures. Changes in the C8 NMR chemical shift of guanosines following rG substitution at their 3'-side within the quadruplex core strongly suggest the presence of C8-H center dot center dot center dot O hydrogen-bonding interactions with the O2' position of the C2'-endo ribonucleotide. A geometric analysis of reported high-resolution structures indicates that such interactions are a more general feature in RNA quadruplexes and may contribute to the observed preference for parallel topologies.