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Structure and K+ ion-dependent stability of a parallel-stranded DNA quadruplex containing a core A-tetrad
Mark S Searle1, Huw E L Williams, Cathal T Gallagher
1School of Chemistry, Centre for Biomolecular Sciences, University Park, Nottingham, UK NG7 2RD.
Organic & Biomolecular Chemistry
|March 10, 2004
Abstract:
The c-MYC oncogene, containing the DNA 5'-GGAGG repeat sequence, is emerging as an attractive target for anti-cancer therapeutics with evidence to suggest that DNA quadruplex formation is involved in regulating gene transcription. We describe NMR studies and molecular dynamics (MD) simulations on intermolecular quadruplex structures containing the purine-rich GGAGG motif which we show readily assembles to form stable parallel-stranded quadruplexes containing A- and G-tetrads with evidence for weak sequence-specific K(+) ion binding at the 5'-GA step.