PUI-RESEARCH-MILLSAPS-KRAMER

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The nitrogen onium salts (nitrogen heteroaromatic compounds with a N-alkoxy substituent) are photoactivatable compounds that yield a heteroaromatic radical cation and alkoxy radical upon photon absorption. These species have been characterized by laser flash photolysis and the efficiency (quantum yield) of this homolytic cleavage reaction has been determined to be ~ 0.6. Both of there transient species are known to cleave DNA, each with a different mechanism. To be efficient, the species have to be generated in DNA, dictating a strong binding event between the onium salt precursor and DNA. To optimize the potential of the onium salts the goal of this project is to test and improve them for in vitro and in vivo DNA cleaving using Saccharomyces cerevisiae as a test system. The project is divided into several parts: 1.) Synthesis and characterization of new onium salts 2.) Photochemistry and photophysics of the new onium salts 3.) DNA binding and DNA cleavage efficiency 4.) Photobiological impact on Saccharomyces cerevisiae