Effect of linker modification on the biochemical properties of DNA-methylating molecules targeted to estrogen receptor-positive cells.
Presentation
Overview
Overview
Description
New compounds that are capable of causing cytotoxic, non-mutagenic damage to DNA in cells that express the estrogen receptor are being developed in our laboratory. These compounds consist of a DNA-methylating component that binds to the minor groove of DNA at A/T-rich sequences and therefore methylates N3-adenines at these sequences, and an estrogen receptor targeting component. The lead compound that was first synthesized in this series was shown to produce predominantly the desired N3-methyladenine adduct, and exhibited toxicity in MCF-7 breast cancer cells. In order to optimize the desired biological properties of this compound, two new compounds have been synthesized that vary in the composition of the linker that connects the DNA-binding unit with the cell-targeting unit, since alterations in this linker can modulate both DNA-interaction and cell-interactions of the molecules. In this poster, we present the syntheses of these compounds, and compare the properties of these new compounds with those of the lead compound in order to understand the effect of the modifications in the linker on the biological properties of these molecules.
