Design and synthesis of DNA minor groove methylating compounds that target pancreatic 7-cells
- UNCW Author/Contributor (non-UNCW co-authors, if there are any, appear on document)
- Andrew McIver (Creator)
- Institution
- The University of North Carolina Wilmington (UNCW )
- Web Site: http://library.uncw.edu/
- Advisor
- Sridhar Varadarajan
Abstract: The design of compounds that form cytotoxic, non-mutagenic 3-methyladenine adducts
in pancreatic ß-cells is being studied in this project for potential applications in the treatment of
diseases such as diabetes and cancer. These compounds are composed of three components: 1)
a cell-targeting moiety, glucosamine, which targets the insulin producing pancreatic ß-cells by
way of the GLUT-2 transporters present on these cells 2) a site-specific DNA methylating agent,
Me-Lex, which has been shown to selectively produce cytotoxic, non-mutagenic N3-
methyladenine adducts 3) a linker component that connects the two other components together.
The linker is a critical component because it has to be such that the cell-targeting and DNAmethylating
properties of the two functional components are maintained. A synthetic route was
explored, which enables the easy introduction of various linkers into the molecules. Fluorescent
compounds were also designed to bind weakly to DNA at the same positions as the DNAmethylating
compounds. These fluorescent compounds will be used to calculate the binding
constants of weakly binding compounds that bind to the minor groove of DNA at A/T rich
regions. The design features and the synthesis of these compounds are described.
Design and synthesis of DNA minor groove methylating compounds that target pancreatic 7-cells
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Created on 1/1/2009
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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
- Cancer--Chemotherapy, Cancer cells, Molecular biology, Pancreatic beta cells, Streptozotocin
- Subjects
- Molecular biology
- Streptozotocin
- Pancreatic beta cells
- Cancer -- Chemotherapy
- Cancer cells