Synthesis of compounds capable of producing cytotoxic N3-methyladenine DNA adducts in estrogen receptor positive cells
Year: 2009
Type: article
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.
Author: Heather N. Perry
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W1509650061