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Research Abstracts Online
January 2010 - March 2011

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University of Minnesota Twin Cities
College of Pharmacy
Department of Medicinal Chemistry

PI: Shana J. Sturla

Molecular Models of Synthetic Nucleoside Probes and DNA Adducts 

Cancer incidence is linked to environmental factors that can give rise to genomic alterations. These mutations are initiated by carcinogen-induced structural changes that reflect the critical and fundamentally chemical first step in the complex process of cancer development, which involves the formation of DNA adducts. Structural characteristics of DNA adducts can strongly influence their biological impact by disrupting the DNA double helix and influencing its interactions with enzymes such as DNA repair system, polymerases, and other DNA binding proteins. In order to prevent diseases related to genomic instability, it is important to understand molecular level details regarding these interactions and the physical factors that control them. One approach involves the use of synthetic nucleoside probes that specifically pair with DNA adducts. The development of such probes will require a structure-based understanding of relevant physical interactions, and a model that accounts for these interactions in duplex DNA and in the active site of DNA polymerases. The information from computational and modeling studies will guide concurrent laboratory experiments expected to elucidate how certain chemicals initiate cancer, and lead to new diagnostic tools and prevention strategies.

Group Member

Hailey L. Gahlon, Graduate Student