An iterative templated synthesis strategy for the evolution of DNA-binding small molecules

ORGN 414

Christine L. Heinecke, Department of Chemistry, James Madison University, MSC 4501, Harrisonburg, VA 22807 and Christian Melander, Department of Chemistry, North Carolina State University, Raleigh, NC 27695.
Cell permeable small molecules with the ability to bind the major groove of DNA are attractive candidates for controlling gene expression. The paucity of small molecules that bind the major groove of DNA renders the approach of using known DNA binding ligands as a platform for rational drug design impractical. To overcome this hurdle, we are developing a DNA-templated approach to develop ligands that bind sequence selectively to the major groove of DNA. We are synthesizing amino-formyl modified nucleosides and peptide nucleic acids as monomers to evolve a thermodynamically favored ligand with the ability to bind DNA in a sequence specific fashion. To promote recognition along a predefined sequence, we are synthesizing tris(heteroleptic) transition metal complexes as DNA intercalators to promote polymerization at a defined position in the DNA target. The generality of this approach will allow unparalleled flexibility in targeting DNA sequences and will provide additional avenues for targeting diseases on the genomic level.
 

New Reactions and Methodology, Bioorganic Chemistry, Molecular Recognition and Self Assembly
8:00 PM-10:00 PM, Tuesday, 28 March 2006 Georgia World Congress Center -- Ex. Hall B4, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 27 March 2006 Georgia World Congress Center -- Ex. Hall B4, Sci-Mix

Division of Organic Chemistry

The 231st ACS National Meeting, Atlanta, GA, March 26-30, 2006