CHEM & BIOL OF DNA ADDUCT: ANALYSIS OF DNA ADDUCTS HAVING MULTIPLE CONFORMATIONS

化学

• 批准号: 6309198
• 负责人: Michael P Stone
• 金额: $ 0.75万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-15 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6309198
• 关键词: biological products; biomedical resource; nuclear magnetic resonance spectroscopy; nucleic acids

Conformational heterogeneity is emerging as a common feature of oligodeoxynucleotides adducted with chemical carcinogens. Spectroscopically, conformational heterogeneity introduces several problems. First, resonance signals arising from each conformation present in the sample must be individually resolved and identified. Second, conformational heterogeneity reduces the effective sample concentration. Third, methodology for structural refinement of these adducts is not well-developed. Ultra high field NMR provides an attractive method for examining conformationally labile samples because of its extraordinary resolving power and sensitivity, to help identify and assign resonances which arise from conformation exchange. We propose to take advantage of this to develop a better understanding of the conformational equilibria involved for styrene oxide and benzo[a]pyrene adducts of adenine, in an effort to correlate adduct structure with function.

构象异质性正在成为 与化学致癌物加成的寡脱氧核苷酸。 从光谱上讲，构象异质性引入了几个 有问题。首先，每个构象产生的共振信号 样品中存在的物质必须单独分解和鉴定。 第二，构象非均质性减少了有效样本 集中精神。第三，结构精细化的方法论 加合物不发育。超高场核磁共振提供了一种 研究构象不稳定样品的吸引人的方法 由于其非凡的分辨率和敏感度，帮助 识别和分配由构象交换引起的共振。 我们建议利用这一点来更好地理解 环氧苯乙烷和环氧苯乙烷的构象平衡 苯并[a]芘与腺嘌呤的加合物，以努力关联加合物 具有功能的结构。