The Synthesis and Chemistry of Modified DNA Nucleobases

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DNA comprises the canonical nucleobases G, C, T and A plus a number of natural, chemically modified nucleobases that include 5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine. The overall aims of the project are to understand the chemistry, the incidence and the function of modified nucleobases in DNA using chemical approaches. The project work will involve the development of synthetic chemistry to prepare nucleosides, phoshoramidites and triphosphate derivatives of monomers that comprise modified bases such as those mentioned. Part of the project will involve the synthesis of oligonucleotides that comprise one or more modified bases in addition to canonical nucleobases. The fundamental physical and chemical properties of DNA that includes modified bases will be evaluated using biophysical and spectroscopic techniques. Another aspect of the project will involve the development of chemoselective approaches for converting modified bases in the context of a DNA strand for applications that will include the detection and sequencing of base modification in DNA.