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Τρίτη 5 Φεβρουαρίου 2019

Fuel‐responsive allosteric DNA‐based aptamers for the transient release of ATP and cocaine

Allostery is generally considered as a thermodynamic equilibrium phenomenon. In contrast to this, we show here that this mechanism offers a key strategy to rationally design out‐of‐equilibrium synthetic devices. We demonstrate this by engineering allosteric DNA‐based nanodevices for the transient load and release of small organic molecules. To demonstrate the versatility and generality of our approach we have employed two model DNA‐based aptamers that bind ATP and cocaine through a target‐induced conformational change. We have rationally 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 temporal release of ATP or cocaine from the aptamers. Our approach confirms how 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 different kinds of small molecule cargoes (ATP and cocaine) and to rationally design non‐equilibrium systems. Moreover, our study illustrates the potential of transient allosteric regulation as a tool to control the functions of synthetic dissipative devices.



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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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