Design of small molecule drugs targeting quadruplex nucleic acids

ORGN 323

Stephen Neidle, stephen.neidle@pharmacy.ac.uk, Cancer Research UK Biomolecular Structure Group, School of Pharmacy, University of London, 29-39 Brunswick Square, London, WC1N 1AX, United Kingdom
Four-stranded nucleic acids can be formed from DNA or RNA sequences containing at least four short guanine tracts. These are found at the telomeric ends of eukaryotic chromosomes, and also within genes, especially in promoter regions of a number of oncogenes. Quadruplex DNAs can form a wide range of topologies, and the resulting three-dimensional structures can be specifically recognized by small-molecule ligands. Telomeric quadruplex complexes with small molecules can inhibit the action of telomerase, which plays a key role in tumor maintenance and immortalization. Recent crystal structures of telomeric quadruplex complexes with several ligands have established the features required for effective quadruplex binding and selectivity. These are being incorporated in the development of 2nd generation telomere targeting agents.
 

Small Molecule Therapeutic Agents
8:30 AM-11:50 AM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- 207A, Oral

Division of Organic Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009