Fuel-Responsive Allosteric DNA-Based Aptamers for the Transient Release of ATP and Cocaine
Fuel-Responsive Allosteric DNA-Based Aptamers for the Transient Release of ATP and Cocaine
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DOI：
10.1002/anie.201812885
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发表时间：
2019-04-16
影响因子：
16.6
通讯作者：
Ricci, Francesco
中科院分区：
文献类型：
--
作者：
Del Grosso, Erica;Ragazzon, Giulio;Ricci, Francesco
我们在此表明，变构提供了一个关键的策略，设计出的平衡系统的工程变构DNA为基础的纳米器件的瞬态加载和释放的小有机分子。为了证明我们的方法的一般性，我们使用了两个模型DNA为基础的适配体，结合ATP和可卡因通过目标诱导的构象变化。我们重新设计了这些适体，使其对特定靶标的亲和力由作为变构抑制剂的DNA序列控制。使用仅在抑制剂与适体结合时特异性切割抑制剂的酶产生导致ATP或可卡因从适体释放的瞬时变构控制。我们的方法证实，核酸的可编程性和可预测性使合成DNA/RNA成为重新设计合成受体的完美候选材料，这些受体可以进行化学燃料触发的小分子货物释放，并合理设计非平衡系统。
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.