The orientation of the ends of G-quadruplex structures investigated using end-extended oligonucleotides

Human telomere DNA is of intense interest because of its role in the biology of both cancer and aging. The single-stranded telomere terminus can adopt the structure of a G-quadruplex, which is of particular important for anticancer drug discovery many researchers have reported various G-quadruplex structures in the human telomere. Although the human telomere consists of a number of tandem repeats, higher-order G-quadruplex structures are less discussed due to the complexity of the structures. Here we examined the orientation of the ends of the G-quadruplex structures with consideration given to higher-order structures. We prepared end-extended and (Br)G-substituted oligonucleotides. Native PAGE analysis, CD measurements and NMR spectroscopy showed that the ends of stable G-quadruplex structures point in opposite directions. Our results indicate that the human telomere DNA is likely to form rod-like higher-order structures. This may provide important information for understanding telomere structure and the development of telomere G-quadruplex-binding molecules as telomerase inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.