Further Investigations of B-Z Junctions in Synthetic DNA Oligomers

将合成特定的DNA寡聚体，以使用模型 帮助理解结构的系统- 某些核酸构象的活性关系。 这些模型构象将被检查与高 通过采用最先进的技术解决问题。它 有人认为Z-DNA可能有助于控制 生物学事件，特别是遗传活动。 尽管直接证据仍然缺乏，或者至少 不完整，建议没有被推翻。 因此 这是非常合理的构象的机制， DNA中的过渡最好在Z-DNA模型上进行研究。 特别是，该项目的主要目标是扩大 已经完成的B-Z结构分析工作 交叉点 大部分的工作将包括一个B-Z结 一个已经很好定义的系统。 有四大 感兴趣的领域：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处或附近碱基对错配的影响 连接;和，4）B-Z连接的过度活跃， 某些致癌物质。 多和多结将 检查许多构象的存在的影响， 连接的整体构象的长DNA寡聚体。 发夹和哑铃中的环的效果以及 结处或附近的失配的影响将是 根据DNA双链体的热力学进行评估， 有问题。它们对生物膜的形成和结构的影响 也将评估该接合处。

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.