Design of compounds for N3-adenine methylation in cells expressing the GLUT2 glucose transporter
Presentation
Overview
Overview
Description
New molecules that are capable of producing cytotoxic, nonmutagenic N3-methyladenine DNA adducts in cells that express the GLUT2 glucose transporter have been designed and synthesized. These molecules contain a site-selective DNA-binding unit, a cell targeting unit, and a DNA-methylating unit. The central DNA-binding component is a bis-pyrrole triamide moiety, that will bind selectively bind to the minor groove of DNA at A/T rich regions. The cell-targeting ligand, a glucosamine unit, is attached to one side of the bispyrrole unit, and is expected to facilitate selective transport of the compounds into cells that express the GLUT2 glucose transporter. At the other side of the bispyrrole unit is tethered a methyl sulfonate unit that can methylate DNA. The linker that connects the bispyrrole unit to the glucosamine unit can influence both DNA-binding and cell-targeting characteristics of the molecule. Therefore, three different molecules, varying in composition of this linker, have been synthesized. These molecules have been tested with genomic DNA for their DNA-methylating properties, and with cells for their toxicity. These results have been compared to the properties of related compounds lacking the cell-targeting glucosamine unit. The design, synthesis and the results of the testing of these molecules with genomic DNA, and with cells, are presented in this poster.
