Further Investigations of B-Z Junctions in Synthetic DNA Oligomers

将合成特定的DNA低聚物，以使用一个模型系统来帮助理解某些核酸构象的构效关系。这些模型的构象将通过使用最先进的技术以高分辨率进行检查。有人认为，Z-DNA可能有助于控制生物事件，特别是遗传活动。尽管仍然缺乏或至少是不完整的直接证据，但这一说法并未被推翻。因此，用Z-DNA模型来研究DNA的构象转变机制是很有可能的。特别是，该项目的主要目标是扩大已经完成的关于B-Z结点结构分析的工作。许多工作将把B-Z结结合到一个已经定义良好的系统中。有四个主要的感兴趣的领域：1)多构象连接；2)DNA发夹和哑铃中的B-Z连接；3)B-Z连接或附近的碱基对错配的影响；以及4)B-Z连接对某些致癌物的过度活性。多重和多重连接将研究许多构象连接的存在对长DNA低聚体整体构象的影响。发夹和哑铃中的环的影响以及连接处或附近的错配影响将根据所讨论的DNA双链的热力学进行评估。还将评估它们对结点的形成和结构的影响。

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.