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.

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

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