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Nucleic Acids Research Advance Access published online on September 6, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn569
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Chemistry and Synthetic Biology

Chiral metallo-supramolecular complexes selectively recognize human telomeric G-quadruplex DNA

Haijia Yu, Xiaohui Wang, Manliang Fu, Jinsong Ren and Xiaogang Qu*

Division of Biological Inorganic Chemistry, Key Laboratory of Rare Earth Chemistry and Physics, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Changchun, Jilin 130022, China

*To whom correspondence should be addressed. Tel: +86 431 8526 2656; Fax: +86 431 85262656; Email: xqu{at}ciac.jl.cn

Received July 4, 2008. Revised August 21, 2008. Accepted August 21, 2008.

Here, we report the first example that one enantiomer of a supramolecular cylinder can selectively stabilize human telomeric G-quadruplex DNA. The P-enantiomer of this cylinder has a strong preference for G-quadruplex over duplex DNA and, in the presence of sodium, can convert G-quadruplexes from an antiparallel to a hybrid structure. The compound's chiral selectivity and its ability to discriminate quadruplex DNA have been studied by DNA melting, circular dichroism, gel electrophoresis, fluorescence spectroscopy and S1 nuclease cleavage. The chiral supramolecular complex has both small molecular chemical features and the large size of a zinc-finger-like DNA-binding motif. The complex is also convenient to synthesize and separate enantiomers. These results provide new insights into the development of chiral anticancer agents for targeting G-quadruplex DNA.


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