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23NA NMR IN DNA QUADRUPLEXES

23NA NMR IN DNA QUADRUPLEXES
DNA 四链体中的 23NA NMR
批准号:
6355123
负责人:
DAVID ROVNYAK
金额:
$1.71万
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-05-01 至 2001-04-30

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中文摘要
翻译
四极核固体核磁共振研究的新进展 允许直接研究生物学中的四极核 大分子。我们对富含鸟嘌呤的化合物进行了2‘Na核磁共振研究 形成G-四链体的DNA寡核苷酸。脱氧核糖核酸 已经提出在端粒末端形成四链,即 染色体的物理末端。DNA四链最近也出现了 作为抗癌药物的潜在靶点,吸引了人们的兴趣。这个 四链体中的鸟嘌呤形成G-四重体,其结构为 由单价阳离子的配位作用稳定,如钠和 钾与四重奏中心的羰基氧原子有关。我们 对四聚体和二聚体四链体进行了2‘Na核磁共振 分别由[d(TG4T)]4和[d(G4T4G4)]2组成,用于识别和 在中心指定多个阳离子结合部位 四联体。我们使用高场强(17.6T)和几个2D 方法获取有价值的分辨率、连通性信息和 赋值,使我们能够区分通道、表面和 游离的钠离子。我们的目标是阐明竞争的机制。 钠与其他阳离子的交换以更好地了解 DNA四链的稳定化。
英文摘要
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.
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23NA NMR IN DNA QUADRUPLEXES
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