Activation of Aptamers with Gain of Function by Small-Molecule-Clipping of Intramolecular Motifs
Mengjiao Huang
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
These authors contributed equally to this work.
Search for more papers by this authorTingyu Li
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
These authors contributed equally to this work.
Search for more papers by this authorYuanfeng Xu
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
Search for more papers by this authorXinyu Wei
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
Search for more papers by this authorDr. Jia Song
Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
Search for more papers by this authorBingqian Lin
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
Search for more papers by this authorProf. Zhi Zhu
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
Search for more papers by this authorCorresponding Author
Dr. Yanling Song
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
Search for more papers by this authorCorresponding Author
Prof. Chaoyong Yang
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
Search for more papers by this authorMengjiao Huang
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
These authors contributed equally to this work.
Search for more papers by this authorTingyu Li
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
These authors contributed equally to this work.
Search for more papers by this authorYuanfeng Xu
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
Search for more papers by this authorXinyu Wei
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
Search for more papers by this authorDr. Jia Song
Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
Search for more papers by this authorBingqian Lin
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
Search for more papers by this authorProf. Zhi Zhu
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
Search for more papers by this authorCorresponding Author
Dr. Yanling Song
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
Search for more papers by this authorCorresponding Author
Prof. Chaoyong Yang
The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005 China
Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
Search for more papers by this authorAbstract
Click reactions have the advantages of high reactivity, excellent orthogonality, and synthetic accessibility. Inspired by click reactions, we propose the concept of “clipped aptamers”, whose binding affinity is regulated by the “clip”-like specific interaction between a synthetic DNA-mismatch-binding small molecule (molecular glue, Z-NCTS) and the preset CGG/CGG sequences in nucleic acid sequences. In this study, we investigated a Z-NCTS-mediated de novo selection of clipped aptamers against epithelial cell adhesion molecule. The generated clipped aptamers can achieve the efficient transition from a binding-inactive state to an active state by clipping of Z-NCTS with two CGG sites, which otherwise would not hybridize. The experimental and simulation results showed that the clipped aptamer had ideal binding thermodynamics and the ability to regulate cellular adhesion. Because of this superior activated mechanism and structural diversity, clipped aptamers hold great potential in biosensing, imaging, conditional gene- and cellular behavior-regulation, and drug delivery.
Conflict of interest
The authors declare no conflict of interest.
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