Redox-Switchable Binding Properties of the ATP–Aptamer

In this study we report a redox-controllable and reversible complete “ON”/“OFF”-switchable aptamer binding to ATP. First, a series of methylene blue modified ATP-aptamers were synthesized revealing improved binding affinities towards ATP as compared to the non-modified aptamer. These binding affinities were dependent on the conjugation site of the redox label on the aptamer scaffold. Importantly, we find that the oxidized methylene blue-modified aptamers bind to the ATP aptamer with micromolar affinity, while the reduced form lacks binding affinity towards ATP, resulting in an unprecedented complete ON/OFF redox controllable aptamer switch. We demonstrate the cyclic “ON”/“OFF” binding of ATP to the methylene blue-functionalized aptamer through cyclic oxida-tion and reduction of the redox label using both chemical and electrochemical means. Molecular dynamics and docking simula-tions were performed to account for the redox-switchable properties of the conjugated aptamers and to rationalize the enhanced bin...