We show herein that allostery offers a key strategy for the design of out-of-equilibrium systems by engineering allosteric DNA-based nanodevices for the transient loading and release of small organic molecules. To demonstrate the generality of our approach, we used two model DNA-based aptamers that bind ATP and cocaine through a target-induced conformational change. We re-engineered these aptamers so that their affinity towards their specific target is controlled by a DNA sequence acting as an allosteric inhibitor. The use of an enzyme that specifically cleaves the inhibitor only when it is bound to the aptamer generates a transient allosteric control that leads to the release of ATP or cocaine from the aptamers. Our approach confirms that the programmability and predictability of nucleic acids make synthetic DNA/RNA the perfect candidate material to re-engineer synthetic receptors that can undergo chemical fuel-triggered release of small-molecule cargoes and to rationally design non-equilibrium systems.
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| http://dx.doi.org/10.1002/anie.201812885 | DOI Listing |
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