Fluorescent DNA Base Analogs

点击翻译按钮获取中文摘要

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.