Synthetic Generation of an Azide-Bearing N-Mustard Cofactor Mimic of S-Adenosyl-L-Methionine
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- abstract
- The synthesis of an azide-bearing
N -mustard cofactor, 8-azido-5’-(diaminobutyric acid)-N -iodoethyl-5’-deoxyadenosine ammonium hydrochloride (2.1 ), has been accomplished with a small amount of impurity in several steps from commercially available 2’,3’-isopropylidene adenosine (2.2 ). This cofactor was designed to efficiently mimicS -adenosyl-L-methionine (SAM) by incorporating anN -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 theC 8 position of the adenine base prior to the incorporation ofN -mustard and amino acid moieties. Cofactor2.1 was found to be effectively transferred onto DNA byM.TaqI , 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. - subject
- DNA Methylation
- Nitrogen Mustard
- S-adenosyl-L-methionine
- contributor
- Comstock, Lindsay R (committee chair)
- Alexander, Rebecca W (committee member)
- King, S. Bruce (committee member)
- date
- 2011-07-14T20:36:30Z (accessioned)
- 2011-07-14T20:36:30Z (available)
- 2011 (issued)
- degree
- Chemistry (discipline)
- identifier
- http://hdl.handle.net/10339/33500 (uri)
- language
- en (iso)
- publisher
- Wake Forest University
- title
- Synthetic Generation of an Azide-Bearing N-Mustard Cofactor Mimic of S-Adenosyl-L-Methionine
- type
- Thesis