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oai:null:10339/335002026-09-18T13:40:58Zcom_10339_14934col_10339_38132

Mai, Van 2011-07-14T20:36:30Z 2011-07-14T20:36:30Z 2011 https://wakespace.lib.wfu.edu/handle/10339/33500 The synthesis of an azide-bearing <italic>N</italic>-mustard cofactor, 8-azido-5’-(diaminobutyric acid)-<italic>N</italic>-iodoethyl-5’-deoxyadenosine ammonium hydrochloride (<bold>2.1</bold>), has been accomplished with a small amount of impurity in several steps from commercially available 2’,3’-isopropylidene adenosine (<bold>2.2</bold>). This cofactor was designed to efficiently mimic <italic>S</italic>-adenosyl-L-methionine (SAM) by incorporating an <italic>N</italic>-mustard and an amino acid moiety surrounding an adenosine core. In addition, an azide functionality was introduced for post-alkylation modification. The crucial factors that led to this success were (1) the choice of the proper alcohol protecting group and (2) the installation of the azide functionality at the <italic>C</italic>8 position of the adenine base prior to the incorporation of <italic>N</italic>-mustard and amino acid moieties. Cofactor <bold>2.1</bold> was found to be effectively transferred onto DNA by <italic>M.TaqI</italic>, providing an azide-bearing modified DNA that will allow for subsequent chemoselective ligation chemistry that is hypothesized to facilitate the detection of biological methylation sites. en Wake Forest University DNA Methylation Nitrogen Mustard S-adenosyl-L-methionine Synthetic Generation of an Azide-Bearing N-Mustard Cofactor Mimic of S-Adenosyl-L-Methionine Thesis Comstock, Lindsay R Alexander, Rebecca W King, S. Bruce Chemistry open.access