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Kieltyka, Roxanne; Englebienne, Pablo; Fakhoury, Johans; Autexier, Chantal; Moitessier, Nicolas; Sleiman, Hanadi F
Journal of the American Chemical Society, 08/2008, Volume: 130, Issue: 31Journal Article
In this contribution, we report that a self-assembled platinum molecular square Pt(en)(4,4′-dipyridyl)4 can act as an efficient G-quadruplex binder and telomerase inhibitor. Molecular modeling studies show that the square arrangement of the four bipyridyl ligands, the highly electropositive nature of the overall complex, as well as hydrogen bonding interactions between the ethylenediamine ligands and phosphates of the DNA backbone all contribute to the observed strong binding affinity to the G-quadruplex. Through thermal denaturation studies with duplex and quadruplex FRET probes and enzymatic assays, we demonstrate that this platinum square strongly binds to G-quadruplexes and can act as an inhibitor of telomerase. This study thus shows the potential of supramolecular self-assembly to readily generate scaffolds of unique geometries for effective targeting of G-quadruplexes and for the ultimate development of selective antitumor therapies.
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