Book of Abstracts: Albany 2011
June 14-18 2011
©Adenine Press (2010)
Efficient B-Z DNA Conformational Transition Induced by Ru(II) Complexes
The left-handed Z-DNA plays important role in biological processes, it can regulate gene expression and involve in DNA processing event such as genetic instability (1). This may provides target for the prevention and treatment of some human diseases (2). However, Z-DNA is a higher energy conformation than B-former, it is a transient structure and intrinsically instable (3). Z-DNA is rarely formed without the help of high salt concentrations or negative supercoiling. It was found in d(CG)n polymer at high salt concentrations (2.5 M NaCl) (4). Recently, the designs of molecules that can induce transition from B to Z conformations and stabilize the Z-DNA have received considerable attention (5).
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, MOE Key Laboratory of Gene Engineering, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China.
In the present work, two new ruthenium complexes [Ru(tpy)(pnt)]2+ (1) and Ru(dmtpy)(pnt)]2+ (2) have been synthesized (tpy = 2,2’:6’,2”-terpyridine, dmtpy = 5,5''-dimethyl-2,2':6',2"-terpyridine, pnt = 2-(1,10-phenanthrolin-2-yl)-naphtho[1,2-e][1,2,4] triazine). Two ruthenium complexes interact with DNA by an intercalation binding mode (6-8). More interesting, they can efficiently convert the B-form of DNA into the Z conformation under physiological salt condition in micromole concentration. This induced left-handed helix is extraordinary stable against high temperature. The mechanism is proposed that complexes insert to DNA base pairs and distort DNA helix structure. Meanwhile, the Ru(II) center reduces electrostatic repulsion of phosphate backbone in the zigzag path of Z-DNA and locks the left-handed conformer irreversible to right-handed helix.
We gratefully acknowledge the supports of the 973 Program, the National Natural Science Foundation of China, the Program for New Century Excellent Talents in University, the Guangdong Provincial Natural Science Foundation and Sun Yat-Sen University.