High-Resolution Insight into G-Overhang Architecture

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• 作者：Robert H盲nsel ; Frank L枚hr ; Luk谩拧 Trantirek ; Volker D枚tsch
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：February 20, 2013
• 年：2013
• 卷：135
• 期：7
• 页码：2816-2824
• 全文大小：424K
• 年卷期：v.135,no.7(February 20, 2013)
• ISSN：1520-5126

文摘

NMR and fluorescence spectroscopy were used to address the effect of intracellular molecular crowding and related hydration on a model telomeric G-quadruplex (G4) DNA structure (d(AG₃(TTAGGG)₃)). d(AG₃(TTAGGG)₃) prevalently adopted the hybrid-1 conformation in vivo, ex vivo, and in dilute potassium-based solution, while it formed the parallel propeller fold in water-depleted potassium-based solution, a commonly used model system for studying intracellular molecular crowding. The dilute potassium-based solution appeared to imitate the properties of the cellular environment required for d(AG₃(TTAGGG)₃) folding under in vivo and ex vivo conditions. High-resolution NMR investigations of site-specifically ¹⁵N-labeled G4 units in native-like single-stranded telomeric DNA revealed that the 3鈥?terminal and internal G4 unit predominantly coexist in 2-tetrad antiparallel basket and hybrid-2 structures that are arranged in 鈥渂eads-on-a-string鈥?like fashion. Our data provide the first high-resolution insight into the telomeric G-overhang architecture under essentially physiological conditions and identify the 2-tetrad antiparallel basket and hybrid-2 topologies as the structural targets for the development of telomere-specific G4 ligands.