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Biochim Biophys Acta. 2013 Oct;1830(10):4935-42. doi: 10.1016/j.bbagen.2013.06.019. Epub 2013 Jun 26.

G-Quadruplex conformational change driven by pH variation with potential application as a nanoswitch.

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School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.



G-Quadruplex is a highly polymorphic structure, and its behavior in acidic condition has not been well studied.


Circular dichroism (CD) spectra were used to study the conformational change of G-quadruplex. The thermal stabilities of the G-quadruplex were measured with CD melting. Interconversion kinetics profiles were investigated by using CD kinetics. The fluorescence of the inserted 2-Aminopurine (Ap) was monitored during pH change and acrylamide quenching, indicating the status of the loop. Proton NMR was adopted to help illustrate the change of the conformation.


G-Quadruplex of specific loop was found to be able to transform upon pH variation. The transformation was resulted from the loop rearrangement. After screening of a library of diverse G-quadruplex, a sequence exhibiting the best transformation property was found. A pH-driven nanoswitch with three gears was obtained based on this transition cycle.


Certain G-quadruplex was found to go through conformational change at low pH. Loop was the decisive factor controlling the interconversion upon pH variation. G-Quadruplex with TT central loop could be converted in a much milder condition than the one with TTA loop. It can be used to design pH-driven nanodevices such as a nanoswitch.


These results provide more insights into G-quadruplex polymorphism, and also contribute to the design of DNA-based nanomachines and logic gates.


Acidic pH; Conformational interconversion; G-Quadruplex; Nanoswitch; Thiazole orange (TO); pH-driven

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