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Design and synthesis of DNA minor groove methylating compounds that target estrogen receptor positive cells

UNCW Author/Contributor (non-UNCW co-authors, if there are any, appear on document)
Tera L. Lynch (Creator)
Institution
The University of North Carolina Wilmington (UNCW )
Web Site: http://library.uncw.edu/

Abstract: The goal of this project is to design and synthesize compounds that can potentially target breast cancer cells selectively, and can cause specific DNA-damage in these tumor cells. The molecules that will be synthesized will consist of 3 components: (a) a component known to selectively methylate the N3-position of adenine in A/T-rich regions of DNA, (b) a component known to target breast cancer cells due to its specific binding to the estrogen receptors (ER) that are over expressed in early stage breast cancer cells, and, (c) a variable linker component, that connects the above two functional components in such a way that the desired properties (DNA-methylation and cell-targeting) are optimized. The specific kind of DNA-damage, the N3-methyladenine adduct, is one that has been shown to cause only cell-death, and not cause mutations. The cell-targeting component chosen is estradiol, which has been often used to deliver agents to breast cancer cells. This thesis discusses the design of these compounds, and the synthetic strategy that has been developed for the preparation of these compounds. The progress towards the synthesis of one of these compounds is also described. Understanding how to target breast cancer cells preferentially, and how to cause only the kind of DNA-damage that results in cell-death, will aid in the design of new drugs that can destroy breast tumors while minimizing unwanted side-effects, and eliminating the incidence of secondary cancers.

Additional Information

Publication
Thesis
A Thesis Submitted to the University of North Carolina at Wilmington in Partial Fulfillment of the Requirement for the Degree of Masters of Science
Language: English
Date: 2009
Keywords
Antineoplastic agents--Design, Apoptosis, Breast--Cancer--Chemotherapy, Cancer--Chemotherapy, Cancer cells, Molecular biology
Subjects
Cancer -- Chemotherapy
Breast -- Cancer -- Chemotherapy
Molecular biology
Antineoplastic agents -- Design
Cancer cells
Apoptosis