Fluorescent bioprobes: structural matching in the docking processes of aggregation-induced emission fluorogens on DNA surfaces.
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.
Hong
Yuning
Y
Department of Chemistry, Nano Science and Technology Program, The Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong, P.R. China.
Xiong
Hao
H
Lam
Jacky Wing Yip
JW
Häussler
Matthias
M
Liu
Jianzhao
J
Yu
Yong
Y
Zhong
Yongchun
Y
Sung
Herman H Y
HH
Williams
Ian D
ID
Wong
Kam Sing
KS
Tang
Ben Zhong
BZ
D001483:Base Sequence; D001665:Binding Sites; D015374:Biosensing Techniques; D002151:Calorimetry; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry*; D054856:G-Quadruplexes; D006367:HeLa Cells; D006801:Humans; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000633:toxicity; D055672:Static Electricity; D013267:Stilbenes / Q000737:chemistry / Q000633:toxicity; D016615:Telomere / Q000378:metabolism; D013816:Thermodynamics
C531393:1,1,2,2-tetrakis(4-(2-triethylammonioethoxy)phenyl)ethene tetrabromide; D005456:Fluorescent Dyes; D000644:Quaternary Ammonium Compounds; D013267:Stilbenes; D004247:DNA