PROBING GUANINE STRUCTURE IN NUCLEIC ACID FOLDING

探究核酸折叠中的鸟嘌呤结构

• 批准号: 2184997
• 负责人: STEVEN E ROKITA
• 金额: $ 17.96万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2184997
• 关键词: chemical models; conformation; guanine; metal complex; nickel; nucleic acid structure

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.

过渡金属配合物引起了人们的广泛关注 生物医学界因其结合某些核酸的能力 结构并促进其位点或附近的化学修饰 绑定。当金属蛋白作用时，这种过程“自然”发生 DNA 或 RNA，当金属毒素或药物选择遗传物质作为 他们的目标，以及当金属配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 系列镍络合物是二次和二次的特殊探针 DNA 和 RNA 中鸟嘌呤的三级结构。实用性及应用 现在将使用明确定义的模型深入探索这些复合物 以及当前感兴趣的大型多核苷酸系统。 对核酸折叠的准确描述必须包括广泛的内容 显着偏离规范的各种构象 双螺旋。对研究核酸多态性有浓厚的兴趣 酸的产生源于二级和三级结构的卓越作用 似乎在遗传的识别、调节和反应中发挥作用 信息。虽然小的寡核苷酸模型可以在大的情况下进行检查 通过物理方法详细描述，较大的系统可能只能表征 通过它们的化学和生物活性。 理想情况下，试剂应 可用于确定每个组的溶剂可及性或 多核苷酸结构中的位点。初步分析表明 本文描述的镍络合物在其绝对性方面是无与伦比的 特异性检测多种非物质之一中的鸟嘌呤残基 沃森-克里克碱基配对安排。 研究将充分确定镍试剂的选择性 含有不匹配、凸出、发​​夹和假结序列的靶标。 寡核苷酸模型已被选择用于这些分析，以便直接 可以在这些化学研究和现有的研究之间得出相关性 从磁共振和晶体学获得的结构结果。 随后的多核苷酸研究将提供关键的新视角 弯曲、十字形和蛋白质-DNA 复合物等结构。 最多 重要的是，镍物种也将应用于许多 具有巨大影响的当代问题。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。