PROBING GUANINE STRUCTURE IN NUCLEIC ACID FOLDING

过渡金属配合物在本领域已经引起了相当大的关注。 因为它们能够结合某些核酸， 结构，并促进化学修饰或附近的网站 约束力当金属蛋白作用于 DNA或RNA，当基于金属的毒素或药物选择遗传物质作为 当金属络合物用作构象特异性时， 核酸探针。这些实验室最近发现了一种 一系列的镍配合物是特殊的探针的第二和 脱氧核糖核酸和核糖核酸中鸟嘌呤的三级结构。实用与应用 现在将使用定义良好的模型深入探讨这些复合体 和当前感兴趣的大的多核苷酸系统。 核酸折叠的准确描述必须包括广泛的 明显偏离规范的各种构象 双螺旋。对研究核酸多态性的极大兴趣 酸的产生是由于二级和三级结构的卓越作用 似乎在识别、调节和反应基因 信息.虽然小的寡核苷酸模型可以在大的寡核苷酸模型中检查， 详细的物理方法，更大的系统可能只被表征 通过它们的化学和生物活性。 理想情况下，试剂应 可用于确定各组的溶剂可及性，或 多核苷酸结构中的一个位点。初步分析表明， 本文所述的镍络合物在它们的绝对 特异性检测鸟嘌呤残基保持在一个数量的非 沃森-克里克碱基配对排列。 研究将充分确定镍试剂的选择性， 含有错配、凸起、发夹和假结序列的靶标。 已选择寡核苷酸模型用于这些分析，以便直接 这些化学研究与现有的化学研究之间可以得出相关性。 从磁共振和晶体学获得的结构结果。 多核苷酸研究将提供一个新的视角， 结构，如弯曲，十字形和蛋白质-DNA复合物。 最 重要的是，镍物质也将应用于许多 当代影响巨大的问题。例如，可访问性 将确定鸟嘌呤的RNA折叠模式，（i）调节 基因翻译和（ii）形成基于RNA的催化剂。

Transition metal complexes have captured considerable attention in the biomedical community because of their ability to bind certain nucleic acid structures and to promote chemical modification at or near the site of binding. Such processes occur "naturally" when metalloproteins operate on DNA or RNA, when metal-based toxins or drugs select genetic material as their target, and when metal complexes are used as conformation specific probes of nucleic acids. These laboratories have recently identified a series of nickel complexes to be exceptional probes for the secondary and tertiary structure of guanine in DNA and RNA. The utility and application of these complexes will now be explored in depth using well defined models and large polynucleotide systems of current interest. An accurate description of nucleic acid folding must include a wide variety of conformations that significantly depart from the canonical double helix. Great interest in studying the polymorphic nature of nucleic acids has arisen from the preeminent role secondary and tertiary structure seems to play in recognition, regulation and reactivity of genetic information. While small oligonucleotide models may be examined in great detail by physical methods, larger systems may only be characterized through their chemical and biological activity. Ideally, reagents should be made available to identify the solvent accessibility of each group or site in a polynucleotide structure. Initial analysis suggests that the nickel complexes described herein are unrivaled in their absolute specificity for detecting guanine residues held in one of a number of non- Watson-Crick base pairing arrangements. Investigations will fully define the nickel reagent's selectivity with targets containing mismatched, bulged, hairpin and pseudoknot sequences. Oligonucleotide models have been chosen for these analyses so that direct correlations can be drawn between these chemical studies and the existing structural results obtained from magnetic resonance and crystallography. Polynucleotide studies will follow to provide a new perspective on key structures such as bends, cruciforms and protein-DNA complexes. Most importantly, the nickel species will also be applied to a number of contemporary problems of enormous impact. For example, the accessibility of guanine will be determined for RNA folding patterns that (i) regulate gene translation and (ii) form RNA-based catalysts.