Ligand-Induced G-Quadruplex Polymorphism: A DNA Nanodevice for Label-Free Aptasensor Platforms

Area of Science:

• Biochemistry and Molecular Biology
• Nanotechnology
• Analytical Chemistry

Background:

• G-quadruplexes (GQs) are crucial recognition elements in DNA aptasensors.
• DNA nanodevices offer controlled conformational changes for sensing mechanisms.
• Label-free detection strategies are highly desirable in biosensing applications.

Purpose of the Study:

• To demonstrate the utility of a G-quadruplex-G-quadruplex (GQ-GQ) nanodevice fueled by GQ-specific ligands as a label-free aptasensor.
• To investigate the impact of ligand-induced topology changes on aptasensor performance.
• To develop a sensitive detection strategy for ochratoxin A (OTA) using this nanodevice.

Main Methods:

• Utilized the human telomeric repeat sequence (H-Telo22) as a model for GQ-GQ nanodevice development.
• Employed a cationic fluorogenic ligand as a GQ-specific light-up probe and nanodevice fuel.
• Investigated the ochratoxin A (OTA) binding aptamer (OTABA) and its ligand-induced conformational changes.

Main Results:

• Ligand-induced topology changes in OTABA (to parallel or hybrid structures) enabled efficient OTA-mediated dye displacement and sensitive OTA detection.
• Failure of the fluorogenic dye to induce a conformational change resulted in poor dye displacement and weak emission response for OTA.
• Demonstrated successful OTA detection with high emission sensitivity when the nanodevice architecture was optimized.

Conclusions:

• This study exemplifies a ligand-induced GQ-GQ nanodevice as a viable aptasensor mechanism.
• The findings highlight the importance of topology-specific GQ binders for diagnostic applications.
• The developed strategy offers a promising label-free approach for sensitive analyte detection.