CAREER: Peptidoconjugates as Models of Protein and DNA Damage

Boston College, Chestnut Hill MA

Investigators

Abstract

Professor Shana Kelley of the Department of Chemistry at Boston College is supported by the Organic and Macromolecular Chemistry Program in the Division of Chemistry and the Biomolecular Systems Program in the Molecular and Cellular Biosciences Division to understand a previously unexplored pathway for DNA damage: the scission of the DNA backbone by oxidized protein residues. Oxidative damage to DNA and proteins is known to be highly deleterious to cellular function, but the interrelationship between the two types of damage events has not been considered. A family of peptide conjugates is under study that models reactions occurring between oxidized protein residues and DNA. A photoactive intercalator contained within the conjugate produces singlet oxygen upon photoexcitation, which reacts with appended residues to generate reactive peroxides that cleave DNA. Professor Kelley studies will identify the amino acids that are most reactive with DNA and will elucidate the chemical mechanism of strand cleavage. She will also investigate how the chemical structures of amino acids impact their reactivities. With support from the Organic and Macromolecular Chemistry Program and the Biomolecular Systems Program Professor Kelley will contribute to the fundamental knowledge about mechanisms of biomolecular deactivation in vivo, an issue of importance to chemists and biologists. The project will also provide interdisciplinary training to graduate, undergraduate, and high school students with diverse backgrounds. The broader impact of the research program will be extended through efforts to actively mentor and recruit talented young women studying the chemical sciences at all levels. A plan is proposed that will provide outreach to women in the Boston area who are considering and pursuing careers in chemistry. The aim of this effort is to prevent attrition and promote an influx of women into high-level positions within academia, industry, and other organizations. Outreach to high school students and teachers is also in progress to increase awareness of the exciting possibilities for careers in chemical research. In addition, continued active mentoring of graduate and undergraduate students will be pursued to ensure that talented young scientists obtain fulfilling and stimulating educational experiences.