Role of adenines in stabilization and exchange kinetics of cations in quadruplex DNA probed by hydrogen-1 and sodium-23 NMR

Cations play a very important role in structural stabilization of various unusual DNA structures. Quadruplexes are a class of unusual DNA structures which are formed by number of single stranded DNA molecules associating by Hoogsteen base pairing. These structures are rich in guanines and there is strong evidence to support that they are formed at the ends of eukaryotic chromosomes. G-quadruplex structures are intimately related to the monovalent cations like sodium and potassium, which are physiologically abundant. The role of these monovalent cations and the effect of substituting terminal thymines with adenines was investigated by multinuclear NMR. The role of terminal thymines in G-quadruplex structure has been established before, but the substitution of thymines and adenines has been dealt here for the first time. The exchange kinetics of cation e.g. 23Na+ from the quadruplex core is determined by the terminal nucleotides present in the oligonucleotide sequence. The sequences d(AAGGGGA), d(AGGGGA) and d(AAGGGGAA) were used to investigate the exchange kinetics of cations from the quadruplex core. Cations bind to the quadruplex structures in namely two ways, weak electrostatic binding and specific binding inside. The flanking adenines slow down the exchange kinetics of the cations from the quadruplex core.