Spectroscopic and Biological Studies of Phenanthroline Compounds: Selectively Recognize Gene Promoter G-quadruplex DNAs over Duplex DNA

Wang Lihua; Wei Chunying

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Spectroscopic and Biological Studies of Phenanthroline Compounds: Selectively Recognize Gene Promoter G-quadruplex DNAs over Duplex DNA

Wang Lihua 1 #,Wei Chunying 2 *

1.Insititude of Molecular Sciencence, Shanxi University, TaiYuan 030006

2.Institude of molecular science, Shanxi University,030006

*Correspondence author

#Submitted by

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Funding: the Selected Research Project Supported by Shanxi Scholarship Council of China and Innovation Foundation for Shanxi Graduate Students of China （No.2009）, Specialized Research Fund for the Doctoral Program of Higher Education （No.20101401110009）, Shanxi Provincial Fund for Natural Sciences （No.2009011012-2）, Research Project Supported by Shanxi Scholarship Council of China （No.2011-016）, the National Natural Science Foundation of China （No.21041008, 21171108）

Opened online:21 December 2012

Accepted by: none

Citation: Wang Lihua,Wei Chunying.Spectroscopic and Biological Studies of Phenanthroline Compounds: Selectively Recognize Gene Promoter G-quadruplex DNAs over Duplex DNA[OL]. [21 December 2012] http://en.paper.edu.cn/en_releasepaper/content/4499807

G-quadruplex DNA formed in the promoter regions of proto-oncogenes would block the transcription process and eventually suppress the development of tumors, so compounds that stabilize G-quadruplex DNA are potential antitumor drugs. This paper studied interactions of three phenanthroline compounds a-c with proto-oncogene c-kit2 and c-myc G-quadruplex DNAs by means of polymerase chain reaction (PCR) stop assay, fluorescence resonance energy transfer melting (FRET melting) assay, fluorescence indicator displacement (FID) assay, UV-vis absorption, fluorescence and circular dichroism (CD) spectroscopies. Results showed that all three compounds presented selectivity for the G-quadruplex over duplex, with binding constants (Ka) for the both quadruplexes varied from 0.49 x 106 to 3.32 x 106 M-1 (4.1- to 33.2-fold specificity). Compounds a, b and c were potential stabilizers for the c-kit2 G-quadruplex with the melting temperature increase (ΔTm) values of 12-15 oC. CD spectra indicated that the three compounds disrupted the structures of c-kit2 G-quadruplex, whereas no significant change was observed for c-myc G-quadruaplex.

Keywords:biological; c-myc; c-kit2; G-quadruplex; promoter; phenanthroline

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