Induction of duplex to G-quadruplex transition in the c-myc promoter region by a small molecule

A major control element of the human c-myc oncogene is the nuclease-hyperse nsitive purine/pyrimidine-rich sequence. This double-stranded DNA fragment, corresponding to the 27-base pair segment in the nuclease-hypersensitive e lement of the c-myc promoter region, forms a stable Watson-Crick double hel ix under physiological conditions. However, this duplex DNA can be effectiv ely converted to G-quadruplex DNA by a small molecular weight ligand. Both intermolecular and intramolecular G-quadruplex forms can be induced by this ligand. Similar transitional changes are also observed with the duplex tel omeric sequence from the Oxytricha species. These results provide additiona l support to the idea that G-quadruplex structures may play structural role s in vivo and also provide insight into novel methodologies for rational dr ug design. These structurally altered DNA elements might serve as regulator y signals in gene expression or in telomere dynamics and hence are promisin g targets for drug action.