Book of Abstracts: Albany 2007
June 19-23 2007
Conformation Conversion and Stabilization of G-Quadruplex by Dinuclear RuII Complex [(bpy)2Ru(obip)Ru(bpy)2]4+
G-quadruplex DNA has been linked to mechanisms that relate to a number of diseases via interfering with telomere maintenance by telomerase. Small molecules able to induce and/or stabilize G-quadruplex structures have been intensively studied for their ability to inhibit telomerase activity and act as potential anticancer agents (1-3). Herein, we report the remarkable ability of a new dinuclear RuII complex [(bpy)2Ru(obip)Ru(bpy)2]4+ to promote the structure conversion and stabilize the human telomeric repeat AG3(T2AG3)3 quadruplex. The experiment results indicated that the concentration of RuII had a significant effect on the conformational change of the G-quadruplex. It could induce positive Tm shifts of +9.4 and +5.8 °C in Na+ and K+ buffer, respectively, in which an increase in the melting temperature of the quadruplex indicated a stabilizing effect. Binding stoichiometry with quadruplex was investigated through luminescence based Job plots. The major inflection points for RuII complex at x=0.48 were observed. These data were consistent with a 1:1 [quadruplex]/[complex] binding mode, which was suggestive of a specific Ru-quadruplex interaction with a single guanine tetrad.
We are grateful to the National Natural Science Foundation of China. The Research Fund for the Doctoral Program of Higher Education, the Natural Science Foundation of Guangdong Province, the Planned Item of Science and Technology of Guangdong Province, and the Item of Tackle Key Problem of Science and Technology of Guangzhou City.
References and Footnotes
1Key Laboratory of Bioinorganic and Synthetic Chemistry of Ministry of Education