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Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
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.

Acknowledgements

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
  1. S. Neidle and G. Parkinson. Nat Rev Drug Discovery 1, 383-393 (2002).
  2. P. Alberti, L. Lacroix, L. Guittat, C. Hélène, and J.-L. Mergny. Mini Reviews in Medicinal Chemistry 3, 23-36 (2003).
  3. W. Li, M. Zhang, J.-l. Zhang, H.-q. Li, X.-c. Zhang, Q. Sun, C.-m. Qiu. FEBS Letters 580, 4905-4910 (2006).

Shuo Shi1
Caiping Tan1
Jie Liu1
Liangnian Ji1, 2, *

1Key Laboratory of Bioinorganic and Synthetic Chemistry of Ministry of Education
School of Chemistry and Chemical Engineering
Sun Yat-Sen University
Guangzhou 510275 China
2Department of Chemistry
Tongji University
Shanghai 200092 PR China

*Phone: +86-20-8411-0558
Fax: +86-20-8403-5497
Email: cesjln@mail.sysu.edu.cn