Fluorescent DNA Base Analogs

圣地亚哥大学化学系的Deborah Tahmassebi博士得到了化学系有机和高分子计划的支持，该计划的目的是探索合成新的基于芘的荧光DNA碱基类似物。商业上可以买到的，基于荧光的芘类芳香族化合物将被卤化，转化为相应的格氏试剂，并与氯化镉反应，得到有机镉衍生物。以市售2-脱氧-D-核糖为原料合成1(α)-氯-2-脱氧-D-呋喃核糖双(对甲苯酸)，并与有机镉衍生物反应得到所需的荧光核苷。通过消除与Lumiphore的柔性碳氢化合物连接，这种方法消除了目前可用的探测器固有的模糊性。将建立荧光核苷的光谱性质，并与DNA结合的核苷的光谱性质进行比较，以探索核酸在溶液中的微结构和环境。考虑到人们对确定DNA的解决方案相结构的兴趣，在Tahmassebi博士职业生涯的这一点上，一项研究计划拨款将为NSF的竞争性提案提供基础。分子结构是决定分子性质的重要因素。大型生物聚合物，如DNA，具有灵活的结构，具有不同的构型，因此在流体溶液中具有不同的性质。这里开发的合成方法学将提供一系列可以被结合到DNA中的荧光核苷。然后，结合的分子的荧光被用作双链DNA形成的动力学和流体溶液中生物聚合物的结构的光谱探针。

Dr. Deborah Tahmassebi, Department of Chemistry, University of San Diego is supported by the Organic and Macromolecular Program of the Chemistry Division under a Research Planning Grant to explore the synthesis of new pyrene-based fluorescent DNA base analogues. Commercially available, fluorescent pyrene based aromatics will be halogenated, converted to the corresponding Grignard reagent, and reacted with cadmium chloride to afford the organocadmium derivative. 1(alpha)-chloro-2-deoxy-D-ribofuranosyl bis(p-toluate) will be synthesized from commercially available 2-deoxy-d-ribose and reacted with the organocadmium derivative to achieve the desired fluorescent nucleoside. By eliminating the flexible hydrocarbon link to the lumiphore, this methodology removes the ambiguity inherent in currently available probes. The spectroscopic properties of the fluorescent nucleoside will be established and compared to those of the nucleoside incorporated into DNA to probe the micro-structure and -environment of the nucleic acid in solution. Given the interest in determining the solution phase structure of DNA, a Research Planning Grant at this point in Dr. Tahmassebi's career will provide the basis for a competitive NSF proposal. Molecular structure is a significant determinant of the properties of a molecule. Large biopolymers, such as DNA, possess flexible structures that assume different configurations, and hence different properties in fluid solution. The synthetic methodology developed here will afford a series of fluorescent nucleosides that can be incorporated into DNA. The fluorescence of the incorporated molecules is then used as a spectroscopic probe of the dynamics of duplex DNA formation and the structure of the biopolymer in fluid solution.