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Structure and Stability of Oxygen-Linked DNA Adducts Derived from Phenolic Toxins

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Title: Structure and Stability of Oxygen-Linked DNA Adducts Derived from Phenolic Toxins
Author: Kuska, Michael S.
Department: Department of Chemistry
Program: Chemistry
Advisor: Manderville, Richard A.
Abstract: A significant focus of nucleic acids research is on the reactivity of electrophilic species with DNA to form addition products (adducts). Phenols are known to be able to form adducts at the C8 site of deoxyguanosine (dG). This dissertation studies the oxygen (O)-linked class of phenolic dG adducts for their hydrolytic stability as well as their structural impact on the DNA duplex. To determine the effect of C8 O-linked phenolic dG adducts on glycosidic bond stability spectrophotometric determination of hydrolysis kinetics was performed. The kinetics establish the adducts to be less stable than native dG in acid, but surprisingly stable under physiological conditions. Then to assess the modified duplex structure, a C8 O-linked phenolic dG adduct was incorporated into a DNA duplex. Thermal melting analysis establish the adduct as having a destabilizing effect on the regularly paired duplex and the conformational analysis suggests the phenolic lesion to be weakly mutagenic.
URI: http://hdl.handle.net/10214/6760
Date: 2013-05
Rights: Attribution-NoDerivs 2.5 Canada


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Attribution-NoDerivs 2.5 Canada Except where otherwise noted, this item's license is described as Attribution-NoDerivs 2.5 Canada