Label-free electrochemical selection of G-quadruplex-binding ligands based on structure switching.
G-quadruplexes are higher-order DNA and RNA structures formed from G-rich sequences. Ligands that bind and stabilize G-quadruplex DNA structures are of significant interest because of their potential to inhibit telomerase and halt tumor cell proliferation. This paper demonstrated a label-free electrochemical method for the selection of quadruplex-binding ligands using the electroactive complex [Ru(NH(3))(6)](3+) (RuHex) as signal transducer. The assay exploits the electrostatic interactions between RuHex and anionic phosphate backbones of DNA strands. In the presence of quadruplex-binding ligand, the oligonucleotide of the human telomeric sequence folded into a G-quadruplex structure, as a result, the adsorption amount of RuHex reduced and the peak current decreased. Six traditional Chinese medicine monomers were investigated as potential ligands using proposed method. To further study the interaction of GDNA with drugs, the competition between daidzein and complementary DNA of GDNA has been studied. The combined data from CD spectroscopy, melting curve and electrochemical measurements indicated that ligands selected by this electrochemical method could induce the GDNA folding into G-quadruplex. So this electrochemistry method offers a simple and effective approach to identify ligands with potential anticancer activity.
Jin
Yan
Y
Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Materials Science, Shaanxi Normal University, Xi'an, PR China. jinyan@snnu.edu.cn
Li
Hongyan
H
Liu
Ping
P
D001483:Base Sequence; D015374:Biosensing Techniques / Q000379:methods*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D055664:Electrochemical Techniques / Q000379:methods*; D054856:G-Quadruplexes; D006801:Humans; D007529:Isoflavones / Q000737:chemistry; D008024:Ligands; D010084:Oxidation-Reduction; D055672:Static Electricity; D019098:Telomerase / Q000037:antagonists & inhibitors; D016615:Telomere / Q000737:chemistry
D004365:Drugs, Chinese Herbal; D007529:Isoflavones; D008024:Ligands; C004742:daidzein; D004247:DNA; D019098:Telomerase