Further Investigations of B-Z Junctions in Synthetic DNA Oligomers

合成 DNA 寡聚物中 B-Z 连接的进一步研究

• 批准号: 8816728
• 负责人: Richard Sheardy
• 金额: --
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-15 至 1989-06-01
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8816728&HistoricalAwards=false
• 关键词: Further; Investigations; Junctions; Synthetic; DNA

Specific DNA oligomers will be synthesized to use a model systems to aid in the understanding of the structure- activity relationship of certain nucleic acid conformations. These model conformations will be examined with high resolutions by employing state of the arts techniques. It has been suggested that Z-DNA may contribute to the control of biological events, in particular, genetic activities. Although direct evidence is still lacking or at least incomplete, the suggestion has not been disproved. Therefore it is very plausible that mechanisms of conformational transition in DNA are best studied on Z-DNA models. In particular, the primary goal of this project is to expand the work already completed on the structural analysis of B-Z junctions. Much of the work will incorporate a B-Z junction into an already well defined system. There are four major areas of interest: 1) multiple and poly conformational junctions; 2) B-Z junctions in DNA hairpins and dumbbells; 3) the effects of base pair mismatches at or near a B-Z junction; and, 4) the hyperactivity of B-Z junctions to certain carcinogens. Multiple and poly junctions will examine the effect of the presence of many conformational junctions on the global conformation of a long DNA oligomer. The effects of the loops in hairpins and dumbbells and the effects of mismatches at or near a junction will be evaluated in terms of the thermodynamics of the DNA duplexes in question. Their effects on the formation and structure of the junction will also be evaluated.

将合成特定的 DNA 寡聚物以使用模型系统来帮助理解某些核酸构象的结构-活性关系。 这些模型构象将通过采用最先进的技术以高分辨率进行检查。有人提出，Z-DNA 可能有助于控制生物事件，特别是遗传活动。 尽管直接证据仍然缺乏或至少不完整，但该建议尚未被反驳。 因此，DNA 构象转变机制最好在 Z-DNA 模型上研究是非常合理的。 特别是，该项目的主要目标是扩展 B-Z 交叉点结构分析已完成的工作。 大部分工作将把 B-Z 连接合并到一个已经明确定义的系统中。 有四个主要兴趣领域：1）多重和多构象连接； 2）DNA发夹和哑铃中的B-Z连接； 3) B-Z 连接处或附近的碱基对错配的影响； 4) B-Z 连接对某些致癌物过度活跃。 多重连接和多连接将检查许多构象连接的存在对长 DNA 寡聚物整体构象的影响。 发夹和哑铃中的环的影响以及连接处或附近的错配的影响将根据所讨论的 DNA 双链体的热力学进行评估。还将评估它们对结的形成和结构的影响。