CAREER: Redox-Mediated Cleavage of Peptides and Nucleic Acids

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This CAREER award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports research on the design, synthesis and study of a series of imide chromophores to photochemically cleave DNA, by Professor Lisa Kelly of the Department of Chemistry and Biochemistry at the University of Maryland-Baltimore County. Thymidine sites will be targeted and cleavage of guanine will be measured. The photosensitizers will be recycled in the presence of oxygen and double stranded nucleic acid cleavage will be possible. Macrocycles will be covalently attached to the chromophores and a variety of metal ions coordinated to them. These metal ions will include Zn(II) (pyrimidine-specific), Cd(II) and Pb(II) (heavy atoms), and Co(III) and Cu(II) (electron acceptors). By use of these metal complexes the effect of site-targeting, increased excited state triplet yield, and electron-hole separation after photoactivation will be determined. These investigations will provide information on the mechanism of oxidative damage in nucleic acid polymers, specifically on the relationship between the initial site of redox reactivity and the final site of cleavage.The goal of this research is to develop optimized photoactive compounds which can be used to cleave DNA at specific sites in a well-understood manner. These compounds will be useful for fundamental studies of DNA damage and also find application to genomic sequencing and phototherapy. Using the photosciences as a cross-disciplinary unified forum, inquiry-based curricular revisions will be made to both the undergraduate advanced laboratory and graduate courses. A regional undergraduate research symposium in the chemical and biological sciences has been organized which will help prepare the participating students for careers in industry as well as for advanced graduate training.