TY - JOUR
T1 - Redox-Switchable Binding Properties of the ATP-Aptamer
AU - Biniuri, Yonatan
AU - Luo, Guo Feng
AU - Fadeev, Michael
AU - Wulf, Verena
AU - Willner, Itamar
N1 - Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/10/2
Y1 - 2019/10/2
N2 - In this study, we report on a redox-controllable and reversible complete "ON"/"OFF"-switchable aptamer binding to ATP. A series of methylene blue-modified ATP-aptamers was synthesized, revealing improved binding affinities toward ATP as compared to the nonmodified 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 ATP with micromolar affinity, while the reduced form lacks binding affinity toward 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 oxidation and reduction of the redox label using both chemical and electrochemical means. Molecular dynamics and docking simulations were performed to account for the redox-switchable properties of the conjugated aptamers and to rationalize the enhanced binding affinities of the different aptamer designs.
AB - In this study, we report on a redox-controllable and reversible complete "ON"/"OFF"-switchable aptamer binding to ATP. A series of methylene blue-modified ATP-aptamers was synthesized, revealing improved binding affinities toward ATP as compared to the nonmodified 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 ATP with micromolar affinity, while the reduced form lacks binding affinity toward 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 oxidation and reduction of the redox label using both chemical and electrochemical means. Molecular dynamics and docking simulations were performed to account for the redox-switchable properties of the conjugated aptamers and to rationalize the enhanced binding affinities of the different aptamer designs.
UR - http://www.scopus.com/inward/record.url?scp=85072848566&partnerID=8YFLogxK
U2 - 10.1021/jacs.9b06256
DO - 10.1021/jacs.9b06256
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C2 - 31478647
AN - SCOPUS:85072848566
SN - 0002-7863
VL - 141
SP - 15567
EP - 15576
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 39
ER -