Further Investigations of B-Z Junctions in Synthetic DNA Oligomers

将合成特定的DNA低聚物，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。研究表明，Z-DNA可能对生物事件，特别是遗传活动有控制作用。尽管仍然缺乏直接证据，或者至少是不完整的，但这一建议并没有被反驳。因此，在Z-DNA模型上研究DNA的构象转变机制是非常合理的。特别是，该项目的主要目标是扩展已经完成的B-Z结结构分析工作。大部分工作将把B-Z结纳入一个已经很好的定义系统。有四个主要的兴趣领域：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结处或附近碱基对错配的影响；4) B-Z连接对某些致癌物的过度活跃。多重和多连接将检查许多构象连接的存在对长DNA低聚物的整体构象的影响。发夹和哑铃中的环的影响以及在连接处或连接处附近的不匹配的影响将根据所讨论的DNA双链的热力学进行评估。它们对结的形成和结构的影响也将被评估。

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.