Interaction of an acridine dimer with DNA quadruplex structures. |
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Authors: | P Alberti J Ren M P Teulade-Fichou L Guittat J F Riou J Chaires C Hélène J P Vigneron J M Lehn J L Mergny |
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Institution: | Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM U 201,CNRS UMR 8646, Paris, France. |
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Abstract: | The reactivation of telomerase activity in most cancer cells supports the concept that telomerase is a relevant target in oncology, and telomerase inhibitors have been proposed as new potential anticancer agents. The telomeric G-rich single-stranded DNA can adopt an intramolecular G-quadruplex structure in vitro, which has been shown to inhibit telomerase activity. The C-rich sequence can also adopt a quadruplex (intercalated) structure (i-DNA). Two acridine derivatives were shown to increase the melting temperature of the G- quadruplex and the C-quadruplex at 1 microM dye concentration. The increase in Tm value of the G-quadruplex was associated with telomerase inhibition in vitro. The most active compound, "BisA", showed an IC(50) value of 0.75 microM in a standard TRAP assay. |
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