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MODIFICATION OF CYTOSINE-TARGETED DNA USING N-MUSTARD ANALOGS OF S-ADENOSYL-L-METHIONINE BY EUKARYOTIC DNA METHYLTRANSFERASES

Electronic Theses and Dissertations

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title
MODIFICATION OF CYTOSINE-TARGETED DNA USING N-MUSTARD ANALOGS OF S-ADENOSYL-L-METHIONINE BY EUKARYOTIC DNA METHYLTRANSFERASES
author
Sirasunthorn, Nichanun
abstract
Dysregulation of deoxyribonucleic acid (DNA) methylation in eukaryotes, which requires the universal cofactor donor S-adenosyl-L-methionine (SAM), can result in severe alterations in cellular function and often lead to severe diseases, including carcinogenesis. Although there are many techniques to detect global DNA methylation, the development of site-specific DNA methylation identification techniques is still a shortcoming. Herein, the examination of novel N-mustard analogs of SAM as DNA methylation probes are reported. Critical to the advancement of these analogs has been the functionalization with azides and alkynes capable of undergoing chemoselective ligations. While the successful utility of these N-mustard analogs has been demonstrated with a small panel of prokaryotic DNA methyltransferases (DNMTs) using a model plasmid DNA, the transition to eukaryotic DNMTs has proven challenging owing to the simple recognition sequence (CpG) compared to most prokaryotic enzymes.
contributor
Comstock, Lindsay R (committee chair)
Poole, Leslie B (committee member)
Donati, George L (committee member)
Dos Santos, Patricia C (committee member)
Alexander, Rebecca W (committee member)
date
2019-05-24T08:35:46Z (accessioned)
2021-05-23T08:30:10Z (available)
2019 (issued)
degree
Chemistry (discipline)
embargo
2021-05-23 (terms)
identifier
http://hdl.handle.net/10339/93962 (uri)
language
en (iso)
publisher
Wake Forest University
type
Dissertation

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