Fluorescent Bioprobes: Structural Matching in the Docking Processes of Aggregation-Induced Emission Fluorogens on DNA Surfaces

• Published in: Chemistry : a European journal 2010-01, Vol.16 (4), p.1232-1245
• Main Authors: Hong, Yuning, Xiong, Hao, Lam, Jacky Wing Yip, Häußler, Matthias, Liu, Jianzhao, Yu, Yong, Zhong, Yongchun, Sung, Herman H. Y., Williams, Ian D., Wong, Kam Sing, Tang, Ben Zhong
• Format: Article
• Language: English
• Subjects: aggregation-induced emission; Base Sequence; Binding Sites; Biosensing Techniques; biosensors; Calorimetry; Chemistry; Computer Simulation; Deoxyribonucleic acid; DNA; DNA - chemistry; Fluorescent Dyes - chemistry; fluorescent probes; G-Quadruplexes; HeLa Cells; Humans; Quaternary Ammonium Compounds - chemistry; Quaternary Ammonium Compounds - toxicity; Static Electricity; Stilbenes - chemistry; Stilbenes - toxicity; Telomere - metabolism; Thermodynamics
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200900778

Whereas most conventional DNA probes are flat disklike aromatic molecules, we explored the possibility of developing quadruplex sensors with nonplanar conformations, in particular, the propeller‐shaped tetraphenylethene (TPE) salts with aggregation‐induced emission (AIE) characteristics. 1,1,2,2‐Tetrakis[4‐(2‐triethylammonioethoxy)phenyl]ethene tetrabromide (TPE‐1) was found to show a specific affinity to a particular quadruplex structure formed by a human telomeric DNA strand in the presence of K+ ions, as indicated by the enhanced and bathochromically shifted emission of the AIE fluorogen. Steady‐state and time‐resolved spectral analyses revealed that the specific binding stems from a structural matching between the AIE fluorogen and the DNA strand in the folding process. Computational modeling suggests that the AIE molecule docks on the grooves of the quadruplex surface with the aid of electrostatic attraction. The binding preference of TPE‐1 enables it to serve as a bioprobe for direct monitoring of cation‐driven conformational transitions between the quadruplexes of various conformations, a job unachievable by the traditional G‐quadruplex biosensors. Methyl thiazolyl tetrazolium (MTT) assays reveal that TPE‐1 is cytocompatible, posing no toxicity to living cells. Specific binding: A water‐soluble fluorogen shows a strong emission towards a specific G‐quadruplex structure formed by a human telomeric sequence, but not other DNA conformers, due to the preferred structural matching in the docking process of the fluorogen on the G‐quadruplex surface (see figure) with the aid of electrostatic attraction.