DNA MEDIATED ELECTRON TRANSFER REACTIONS

描述：这项建议寻求继续支持以下研究 描述并应用DNA介导的电子转移。对中国传统文化的研究 DNA p堆叠作为电子转移的媒介在 了解远程径向损伤和修复，在表征中 通过p堆的长距离电荷传输，并在提供 为新一类诊断工具奠定了基础。第一笔赠款的结果 利用金属嵌入剂作为光诱导供体和受体的时期 已经确定了插层p堆积的关键要求 用于快速电子转移。高效光致电子转移 已经证明了金属嵌入物与任何一个 结束15-mer双工(通过p堆栈分离41u)，以及 已经开发了溶液和固相方法来制备一系列 金属-寡核苷酸结合物。瞬变吸收光谱 也被用于DNA介导的反应中，以识别电子 转移中间体，并在超快的时间尺度上建立费率 (1010S-1)。我们现在打算将特征良好的DNA聚合物应用于 (I)确定影响电子转移过程的因素 通过P-系统；(2)详细说明和确定 不同插层给体和不同插层的电子转移化学 接受者；以及(Iii)利用p堆栈开发新的途径 基于DNA的传感器。我们将勾画出长程飞行的参数 一系列电子转移速率测量中的反应 包含系绳金属计算器的双面组件，不同的 在DNA序列、长度和构象上。还将比较费率 在通过两个单金属化合物杂交而构建的双链中 寡核苷酸和双金属链上的双金属。在……里面 通过表征电子转移化学，金属嵌入剂将 根据核心金属、辅助配体和 确定驱动力和堆积效应的立体化学 在价格上。将使用有机嵌入器来确定范围 并提供光谱标记物。一种化学物质 陷阱也被提出，涉及胸腺嘧啶二聚体的修复- 特别是通过光氧化结合到寡核苷酸中 一个Rg嵌入器。电子转移和交换能量转移 将直接在混合金属-DNA组件中进行比较 Ru(II)/Os(III)与Ru(II)/Os(Ii)。新型发光材料的研究进展 提出了对碱基对堆积过程中的扰动敏感的传感器 用DNA螺旋作为一根“线”。程序集将被构造为 检测碱基对不匹配并监控堆叠中的变化 与蛋白质结合相关(HaeIII、EcoRI和TATA-box结合 蛋白质)，并配合抗肿瘤药物，顺式- 二胺铂(II)。该电子转移检测策略提供了 为发展DNA诊断学和 探测溶液中的DNA p堆栈。

DESCRIPTION: This proposal seeks continued support for studies to characterize and apply DNA-mediated electron transfer. The study of the DNA p-stack as a medium for electron transfer is significant in understanding long range radical damage and repair, in characterizing long range charge transport through a p-stack, and in providing the basis for a new class of diagnostic tools. Results in the first grant period using metallointercalators as photoinduced donors and acceptors have established the critical requirement of intercalative p -stacking for fast electron transfer. Efficient photoinduced electron transfer has been demonstrated between metallointercalators tethered to either end of a 15-mer duplex (41u separation through the p-stack), and both solution and solid-phase methods have been developed to prepare a range of metal-oligonucleotide conjugates. Transient absorption spectroscopy has also been used in the DNA-mediated reaction to identify the electron transfer intermediate and, on an ultrafast timescale, to establish rates (1010 s-1). We now intend to apply the well characterized DNA polymer (i) to establish the factors influencing electron transfer processes through p-systems; (ii) to detail and establish the scope for the electron transfer chemistry by varying intercalating donors and acceptors; and (iii) to exploit the p-stack in developing new routes to DNA-based sensors. We will delineate the parameters for the long range reaction in measurements of electron transfer rates on a series of duplex assemblies containing tethered metallontercalators, which vary in DNA sequence, length, and conformation. Rates will also be compared in a duplex constructed through hybridization of two singly metallated oligonucleotides and a duplex doubly metallated on one strand. In characterizing the electron transfer chemistry, metallointercalators will be varied with respect to core metal, ancillary ligands, and stereochemistry to determine the effects of driving force and stacking on rate. Organic intercalators will be employed to establish the scope of this fast reaction and to provide spectroscopic markers. A chemical trap is also proposed, involving the repair of a thymine dimer site- specifically incorporated in an oligonucleotide by photooxidation with a rhodium intercalator. Electron transfer and exchange energy transfer will be compared directly in mixed metal-DNA assemblies constructed with Ru(II)/Os(III) versus Ru(II)/Os(II). The development of new luminescent sensors, sensitive to perturbations in base pair stacking, are proposed using the DNA helix as a "wire". Assemblies will be constructed to detect base pair mismatches and to monitor changes in stacking associated with protein binding (HaeIII, EcoRI, and the TATA-box binding protein) and with coordination of the antitumor agent, cis- diamminePt(II). This electron transfer detection strategy provides a completely new basis for the development of DNA diagnostics and for probing the DNA p-stack in solution.