Microenvironment-Sensitive Fluorescent Ligand Binds Ascaris Telomere Antiparallel G-Quadruplex DNA with Blue-Shift and Enhanced Emission |
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Authors: | Quan-Qi Yu Juan-Juan Gao Xue-Xian Lang Hong-Yao Li Prof Ming-Qi Wang |
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Affiliation: | School of Pharmacy, Jiangsu University, Zhenjiang, 212013 P. R. China |
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Abstract: | The development of small molecules that can selectively target G-quadruplex (G4) DNAs has drawn considerable attention due to their unique physiological and pathological functions. However, only a few molecules have been found to selectively bind a particular G4 DNA structure. We have developed a fluorescence ligand Q1 , a molecular scaffold with a carbazole–pyridine core bridged by a phenylboronic acid side chain, that acts as a selective ascaris telomere antiparallel G4 DNA ASC20 ligand with about 18 nm blue-shifted and enhanced fluorescence intensity. Photophysical properties revealed that Q1 was sensitive to the microenvironment and gave the best selectivity to ASC20 with an equilibrium binding constant Ka=6.04×105 M?1. Time-resolved fluorescence studies also demonstrated that Q1 showed a longer fluorescence lifetime in the presence of ASC20. The binding characteristics of Q1 with ASC20 were shown in detail in a fluorescent intercalator displacement (FID) assay, a 2-Ap titration experiment and by molecular docking. Ligand Q1 could adopt an appropriate pose at terminal G-quartets of ASC20 through multiple interactions including π–π stacking between aromatic rings; this led to strong fluorescence enhancement. In addition, a co-staining image showed that Q1 is mainly distributed in the cytoplasm. Accordingly, this work provides insights for the development of ligands that selectively targeting a specific G4 DNA structure. |
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Keywords: | antiparallel G4 DNA ASC20 carbazoles fluorescent ligands microenvironment-sensitive phenylboronic acid |
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