Tetramolecular DNA quadruplexes in solution: insights into structural diversity and cation movement.

The present study expands the notion that the simple oligonucleotide sequence d(TG(4)T) in solution forms a tetramolecular G-quadruplex having a parallel orientation of the four strands and four G-quartets with all of the residues in the anti orientation. NMR experiments have revealed the equilibrium of two monomeric forms with a ratio between 85:15 and 70:30 in the presence of K(+), Na(+), and (15)NH(4)(+) ions. The major form consists of four G-quartets, whereas the minor form exhibits an additional T-quartet at the 5' end. An analogous oligonucleotide with U at the 5' end adopts a dimeric structure of G-quadruplex units in the presence of K(+) and (15)NH(4)(+) cations but not in the presence of Na(+) ions, where monomeric forms are present. Three (15)NH(4)(+) ion binding sites between the four G-quartets within the major monomeric form have been identified, while an additional (15)NH(4)(+) ion binding site between the G- and T-quartets at the 5' end of the minor form has been established. The dimeric d[(UG(4)T)(4)](2) G-quadruplex exhibits eight (15)NH(4)(+) ion binding sites, two of them between the U- and G-quartets. (15)NH(4)(+) ions have been shown to move faster between the interior of the tetramolecular structures and the bulk solution in comparison with the monomolecular and bimolecular G-quadruplexes. However, cation movement is slowed by the presence of a T-quartet at the 5' end.