Selective recognition of c-MYC Pu22 G-quadruplex by a fluorescent probe
| Autor: | Chunyang Cao, Haitao Hou, Qianqian Zhai, Chao Gao, Yashu Zhang, Jieqin Ding, Hua Deng, Barira Islam, Shengzhen Xu, Hany I. Mohamed, Dengguo Wei, Li Jun, Shozeb Haider, Wenxian Lan, Zhe Hu |
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| Rok vydání: | 2019 |
| Předmět: |
Fluorophore
Cell Survival Aptamer Drug Evaluation Preclinical Genes myc Stacking Molecular Dynamics Simulation Biology Ligands G-quadruplex 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Chemical Biology and Nucleic Acid Chemistry Cell Line Tumor Genetics Humans Fluorescent Dyes 030304 developmental biology chemistry.chemical_classification 0303 health sciences Oligonucleotide Biomolecule Fluorescence G-Quadruplexes Molecular Docking Simulation chemistry Molecular Probes Nucleic acid Biophysics Nucleic Acid Conformation 030217 neurology & neurosurgery |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Nucleic acid mimics of fluorescent proteins can be valuable tools to locate and image functional biomolecules in cells. Stacking between the internal G-quartet, formed in the mimics, and the exogenous fluorophore probes constitutes the basis for fluorescence emission. The precision of recognition depends upon probes selectively targeting the specific G-quadruplex in the mimics. However, the design of probes recognizing a G-quadruplex with high selectivity in vitro and in vivo remains a challenge. Through structure-based screening and optimization, we identified a light-up fluorescent probe, 9CI that selectively recognizes c-MYC Pu22 G-quadruplex both in vitro and ex vivo. Upon binding, the biocompatible probe emits both blue and green fluorescence with the excitation at 405 nm. With 9CI and c-MYC Pu22 G-quadruplex complex as the fluorescent response core, a DNA mimic of fluorescent proteins was constructed, which succeeded in locating a functional aptamer on the cellular periphery. The recognition mechanism analysis suggested the high selectivity and strong fluorescence response was attributed to the entire recognition process consisting of the kinetic match, dynamic interaction, and the final stacking. This study implies both the single stacking state and the dynamic recognition process are crucial for designing fluorescent probes or ligands with high selectivity for a specific G-quadruplex structure. |
| Databáze: | OpenAIRE |
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