Full metadata
Title
Bleomycin, from start to finish: total synthesis of novel analogues to in vitro fluorescence microscopy imaging
Description
The bleomycins are a family of glycopeptide-derived antibiotics isolated from various Streptomyces species and have been the subject of much attention from the scientific community as a consequence of their antitumor activity. Bleomycin clinically and is an integral part of a number of combination chemotherapy regimens. It has previously been shown that bleomycin has the ability to selectively target tumor cells over their non-malignant counterparts. Pyrimidoblamic acid, the N-terminal metal ion binding domain of bleomycin is known to be the moiety that is responsible for O2 activation and the subsequent chemistry leading to DNA strand scission and overall antitumor activity. Chapter 1 describes bleomycin and related DNA targeting antitumor agents as well as the specific structural domains of bleomycin. Various structural analogues of pyrimidoblamic acid were synthesized and subsequently incorporated into their corresponding full deglycoBLM A6 derivatives by utilizing a solid support. Their activity was measured using a pSP64 DNA plasmid relaxation assay and is summarized in Chapter 2. The specifics of bleomycin—DNA interaction and kinetics were studied via surface plasmon resonance and are presented in Chapter 3. By utilizing carefully selected 64-nucleotide DNA hairpins with variable 16-mer regions whose sequences showed strong binding in past selection studies, a kinetic profile was obtained for several BLMs for the first time since bleomycin was discovered in 1966. The disaccharide moiety of bleomycin has been previously shown to be a specific tumor cell targeting element comprised of L-gulose-D-mannose, especially between MCF-7 (breast cancer cells) and MCF-10A ("normal" breast cells). This phenomenon was further investigated via fluorescence microscopy using multiple cancerous cell lines with matched "normal" counterparts and is fully described in Chapter 4.
Date Created
2013
Contributors
- Bozeman, Trevor C (Author)
- Hecht, Sidney M. (Thesis advisor)
- Chaput, John (Committee member)
- Gould, Ian (Committee member)
- Arizona State University (Publisher)
Topical Subject
Resource Type
Extent
xiv, 137 p. : ill. (some col.)
Language
eng
Copyright Statement
In Copyright
Primary Member of
Peer-reviewed
No
Open Access
No
Handle
https://hdl.handle.net/2286/R.I.21005
Statement of Responsibility
by Trevor C. Bozeman
Description Source
Retrieved on March 20, 2014
Level of coding
full
Note
thesis
Partial requirement for: Ph.D., Arizona State University, 2013
bibliography
Includes bibliographical references (p. 131-137)
Field of study: Chemistry
System Created
- 2014-01-31 11:37:48
System Modified
- 2021-08-30 01:36:34
- 3 years 3 months ago
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