Nucleic Acids Research Advance Access originally published online on March 3, 2009
Nucleic Acids Research 2009 37(8):2471-2482; doi:10.1093/nar/gkp055
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Nucleic Acids Research, 2009, Vol. 37, No. 8 2471-2482
© 2009 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.
Structural Biology |
Natural isoflavones regulate the quadruplex–duplex competition in human telomeric DNA
1Key Laboratory of Systems Bioengineering, 2Key Laboratory for Green Chemical Technology, Ministry of Education, School of Chemical Engineering & Technology, Tianjin University, Tianjin 300072 and 3Qilu Hospital of Shandong University, Jinan 250012, Shangdong Province, China
*To whom correspondence should be addressed. Tel: +86 22 27890643; Fax: +86 22 27890643; Email: liwei{at}tju.edu.cn
Received November 22, 2008. Revised January 18, 2009. Accepted January 19, 2009.
Effects of natural isoflavones on the structural competition of human telomeric G-quadruplex d[AG3(T2AG3)3] and its related Watson–Crick duplex d[AG3(T2AG3)3-(C3TA2)3C3T] are investigated by using circular dichroism (CD), ESI-MS, fluorescence quenching measurement, CD stopped-flow kinetic experiment, UV spectroscopy and molecular modeling methods. It is intriguing to find out that isoflavones can stabilize the G-quadruplex structure but destabilize its corresponding Watson–Crick duplex and this discriminated interaction is intensified by molecular crowding environments. Kinetic experiments indicate that the dissociation rate of quadruplex (kobs290 nm) is decreased by 40.3% at the daidzin/DNA molar ratio of 1.0 in K+, whereas in Na+ the observed rate constant is reduced by about 12.0%. Furthermore, glycosidic daidzin significantly induces a structural transition of the polymorphic G-quadruplex into the antiparallel conformation in K+. This is the first report on the recognition of isoflavones with conformational polymorphism of G-quadruplex, which suggests that natural isoflavone constituents potentially exhibit distinct regulation on the structural competition of quadruplex versus duplex in human telomeric DNA.