Constituents of the endogenous exposome include reactive oxygen species, which cause oxidative damage to nucleic acids, proteins, and lipids. It has been shown that such damage to RNA plays a role in the initiation of neurodegenerative diseases, such as Alzheimer’s. To investigate this phenomenon from a molecular level, modified uridines were synthesized and subjected to photolytic activation, generating a C5'-uridinyl radical mimicking the hydrogen atom abstraction observed under conditions of oxidative stress. This was accomplished with a <i>tert</i>-butyl ketone at the C5' position, which undergoes type I Norrish cleavage. Studies were performed under anaerobic and aerobic conditions in the presence or absence of reductant at varying pH to emulate the diversity of the cellular environment. Identification of damage lesions formed in the process may assist in the development of new assays based on biomarkers of oxidative damage.

Investigation into the reactivity of a C5'-uridinyl radical

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.