Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
Dinuclear Ruthenium(II) Complexes as G-Quadruplex DNA
Telomerase is an essential factor in cellular immortalization and tumorigenesis, it has been detected in some 80-90% of all human cancers but in relatively few normal cell types.1 Thus, the inhibition of telomerase activity by inducing/stabilizing G-quadruplex formation is an important approach for developing new anticancer drugs.2 During the past decade many studies have been devoted to the G-quadruplex recognition, and a number of small molecules are found to be able to selectively promote the formation and/or stabilization of G-quadruplex.3 In the present work, a series of dinuclear Ru(II) complexes [(bpy)2Ru(BL)Ru(bpy)2]4+ (BL = mbpibH2, hbibH3 and ebipcH2) were designed and synthesized. CD and FRET melting results indicated that dinuclear Ru(II) complexes selectively promote the formation of antiparallel G-quadruplex structures and induce positive Tm shifts in K+ and Na+ buffer. The Ru(II) complexes as telomerase inhibitors were also examined through the utilization of modified telomerase repeat amplification protocol (TRAP). Ru(II) complexes show high activity for telomerase inhibition. The properties of these Ru(II) complexes make them promising candidates to explore the biological function of G-quadruplexes and form the basis for developing a new class of telomerase inhibitors.
Acknowledgments. We are grateful to the supports of 973 Program of China, NSFC and the Ministry of Education.
References and Footnotes
MOE Lab of Bioinorganic and Synthetic Chemistry