Synthesis of compounds capable of producing cytotoxic N3-methyladenine DNA adducts in estrogen receptor positive cells

UNCW Author/Contributor (non-UNCW co-authors, if there are any, appear on document)
Heather N. Perry (Creator)
The University of North Carolina Wilmington (UNCW )
Web Site:
Sridhar Varadarajan

Abstract: This project describes the design and synthesis of new compounds that are capable of targeting cells that express the estrogen receptor and producing cytotoxic N3-methyladenine DNA adducts in those cells. These compounds contain a reactive methylsulfonate group connected to a unit that binds to DNA in the minor groove at adenine-thymine rich regions, and therefore, selectively methylates adenines in these regions at the N3 position. This component is connected by a linking unit to estradiol, which binds to the estrogen receptor, and therefore, is expected to selectively target these compounds to cells that express the estrogen receptor. The linking unit is the only variable component in the design, and can be altered in order to optimize the DNA and estrogen receptor binding properties of the compound, and to modulate the water solubility of the compounds. The synthesis of three compounds varying in linker length by one, two, and three methylene units is described.

Additional Information

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
Cell receptors, DNA adducts--Synthesis, Estrogen--Receptors, Selective estrogen receptor modulators
Cell receptors
DNA adducts -- Synthesis
Estrogen -- Receptors
Selective estrogen receptor modulators

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