Matching Items (2)
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.
ContributorsBozeman, Trevor C (Author) / Hecht, Sidney M. (Thesis advisor) / Chaput, John (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation is a study and translation of the Hereditary Household of the Han Celestial Master (Han tianshi shijia 漢天師世家), a hagiographical account of successive generations of the Zhang family patriarchs of Celestial Masters Daoism (Tianshi dao 天師道) at Dragon and Tiger Mountain (Longhu shan 龍虎山) in Jiangxi province that was compiled in stages between the late fourteenth and early seventeenth centuries. The Zhang family emerged in the late Tang or early Five dynasties period and rose to great prominence and power through the Song, Yuan, and Ming dynasties on the basis of the claim of direct and unbroken lineal descent from Zhang Daoling 張道陵 the ancestral Celestial Master whose covenant with the deified Laozi in 142 C.E. is a founding event of the Daoist religion. In this study I trace the lineal history of the Zhang family as presented in the Hereditary Household in chronological parallel to contrasting narratives found in official histories, epigraphy, and the literary record. This approach affords insight into the polemical nature of the text as an assertion of legitimacy and allows for a demonstration of how the work represents an attempt to create in writing an idealized past in order to win prestige in the present. It also affords the opportunity to scour the historical record in an attempt to ascertain a plausible timeframe for the origin of the movement and to explore the relationship of the Hereditary Household to earlier hagiographic works that may have informed it. This study also contextualizes the Hereditary Household in the post-Tang religious climate of China. In that period the establishment of lineal authenticity and institutional charisma through narratives of descent became a widespread tool of legitimation employed by Buddhists, Daoists, and Confucians in hopes of obtaining imperial recognition and patronage.
ContributorsAmato, Paul (Author) / Bokenkamp, Stephen R (Thesis advisor) / Chen, Huaiyu (Committee member) / Feldhaus, Anne (Committee member) / West, Stephen H. (Committee member) / Arizona State University (Publisher)
Created2016