Cleavage of telomeric G-quadruplex DNA with perylene-EDTA*Fe(II).
Interest in the development of compounds that bind G-quadruplex DNA selectively has been sparked by the discovery that these compounds can inhibit the activity of telomerase. Compounds that bind to this unique structure, as well as compounds that recognize it and cleave it upon binding, have potential uses as anticancer agents and as probes for the presence of G-quadruplex structures in chromatin. Here we report on the G-quadruplex-specific cleavage properties of a perylene derivative, perylene-EDTA*Fe(II). This water-soluble complex cleaves G-quadruplex DNA selectively in the presence of dithiothreitol. We characterize the cleavage reaction with respect to perylene-EDTA*Fe(II) concentration, DNA structural type, cation type (Na+ vs K+), cation concentration, and pH. Visible spectroscopy confirms the selectivity of the perylene-EDTA*metal complex for G-quadruplex DNA. NMR titration of a parallel G-quadruplex with perylene-EDTA (without metal) indicates that the compound binds to G-quadruplex DNA by stacking externally on the 3' G-tetrad.
Tuntiwechapikul
W
W
Division of Medicinal Chemistry, College of Pharmacy, and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, USA.
Salazar
M
M
D001665:Binding Sites; D002412:Cations / Q000737:chemistry; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000378:metabolism; D004492:Edetic Acid / Q000737:chemistry*; D005296:Ferrous Compounds / Q000737:chemistry*; D054856:G-Quadruplexes; D006863:Hydrogen-Ion Concentration; D010569:Perylene / Q000737:chemistry*; D013057:Spectrum Analysis; D016615:Telomere / Q000235:genetics
D002412:Cations; D005296:Ferrous Compounds; C055526:Fe(II)-EDTA; D010569:Perylene; D004247:DNA; D004492:Edetic Acid; D003851:Deoxyribonucleases