23NA NMR IN DNA QUADRUPLEXES

点击翻译按钮获取中文摘要

Many recent developments in solid-state NMR of quadrupolar nuclei allow for the direct study of quadrupolar nuclei in biological macromolecules. We have carried out a 2'Na NMR study of guanine-rich DNA oligonucleotides that associate to form G-quadruplexes. DNA quadruplexes have been proposed to form at the ends of telomeres, the physical end of chromosomes. DNA quadruplexes have also recently attracted interest as potential targets for anticancer drugs. The guanines in the quadruplexes form G-quartets and the structures are stabilized by coordination of monovalent cations such as sodium and potassium to the carbonyl oxygens in the center of the quartets. We have performed 2'Na NMR on the tetrameric 'and dimeric quadruplexes formed by [d(TG4T)]4 and [d(G4T4G4)]2, respectively, to identify and assign the multiple cation binding sites in the center of the quadruplexes. We use high field strengths (17.6T) and several 2D methods to obtain valuable resolution, connectivi ty informa tion and assignments, allowing us to distinguish between channel, surface and free sodium ions. We aim to clarify the mechanism of competitive exchange of sodium with other cations to better understand the stabilization of DNA quadruplexes.