Fuel‐Responsive Allosteric DNA‐Based Aptamers for the Transient Release of ATP and Cocaine

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.