Selective localization and rotational immobilization of univalent cations on quadruplex DNA.

The quadruplex structure of the oligomer d(T2G4T) is more stable in the presence of K+ than in the presence of Na+. This enhanced stability correlates with the preferential binding of K+ to a small number of specific sites on the quadruplex. In contrast, Na+ and K+ compete on an equal footing for atmospheric binding. Both 39K+ and 23Na+ are, when specifically bound, significantly inhibited in their rotational mobility, so that the quadrupolar relaxation reflects the molecular tumbling of the oligomer, which occurs on the time scale of nanoseconds. This rotational immobilization is in distinct contrast to the high rotational mobility of atmospherically bound cations. On the other hand, all NMR-visible 39K+ in solution is in rapid exchange among all environments (free, specifically bound, and atmospherically bound) implying that the lifetime of specifically coordinated 39K+ must be significantly shorter than a millisecond. A similar conclusion holds for 23Na+. The oligomer d(T2G4T) forms two distinct Hoogsteen base-paired structures in NaCl solution, separated by a large kinetic barrier. Neither of these structures is as stable with respect to base pair opening as is the quadruplex structure formed in KCl solution. Only one of these two structures is associated with rotational immobilization of bound 23Na+.