PROBING GUANINE STRUCTURE IN NUCLEIC ACID FOLDING

探究核酸折叠中的鸟嘌呤结构

• 批准号: 3307052
• 负责人: STEVEN E ROKITA
• 金额: $ 17.52万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 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/3307052
• 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.

过渡金属络合物在化学领域引起了广泛的关注。 生物医学共同体，因为它们有能力结合某些核酸 结构，并促进在或附近的化学修饰 有约束力的。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 它们的目标，以及当金属络合物被用作构象特定的 核酸的探头。这些实验室最近发现了一种 系列镍络合物将成为二次和三次离子的特殊探针 鸟嘌呤在DNA和RNA中的三级结构。实用程序及其应用 现在将使用定义良好的模型深入探索这些复合体中的 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 显著偏离正则构象的各种构象 双螺旋。对研究原子核的多晶性非常感兴趣 酸是由于二级和三级结构的卓越作用而产生的 似乎在基因的识别、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 通过物理方法的详细描述，较大的系统可能仅被描述为 通过它们的化学和生物活性。理想情况下，试剂应该 可用来确定每一组的溶剂可及性或 多核苷酸结构中的结合位点。初步分析表明， 这里所描述的镍络合物在它们的绝对 检测多种非鸟嘌呤中的鸟嘌呤残留量的特异性 沃森-克里克碱基配对安排。 调查将充分定义镍试剂的选择性 包含错配、凸起、发夹和伪结序列的目标。 为这些分析选择了寡核苷酸模型，以便直接 这些化学研究与现有的 从磁共振和结晶学获得的结构结果。 随后将进行多核苷酸研究，为关键基因提供新的视角 弯曲、十字形和蛋白质-DNA复合体等结构。多数 重要的是，镍物种也将适用于一些 影响巨大的当代问题。例如，可访问性 将针对(I)调节的RNA折叠模式确定鸟嘌呤的量 基因翻译和(Ii)形成基于RNA的催化剂。