Wang Guan Alex, Wu Xinghong, Chen Fangfang, Shen Chenlan, Yang Qianfan, Li Feng
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu, Sichuan, China, 610064.
College of Chemistry and Materials Science, Northwest University, Xi'an, Shaanxi, China, 710127.
J Am Chem Soc. 2023 Feb 8;145(5):2750-2753. doi: 10.1021/jacs.2c10928. Epub 2023 Jan 26.
Aptamer switches are attractive nature-inspired tools for developing smart materials and nanodevices. However, the thermal robustness and programmability of current aptamer switches are often limited by their activation processes that are coupled with high reaction enthalpy. Here, we present an enthalpy-independent activation approach that harnesses toehold-exchange as a general framework to design aptamer switches. We demonstrate mathematically and experimentally that this approach is highly effective in improving thermal robustness and thus leads to better analytical performances of aptamer switches. Enhanced programmability is also demonstrated through fine-grained and dynamic tuning of effective affinities and dynamic ranges, as well as the construction of a synthetic DNA network that resembled biological signaling cascades. Our study not only enriches the current toolbox for engineering and controlling synthetic molecular switches but also offers new insights into their thermodynamic basis, which is critical for diverse synthetic biological designs and applications.
适体开关是用于开发智能材料和纳米器件的极具吸引力的受自然启发的工具。然而，当前适体开关的热稳定性和可编程性常常受到其与高反应焓相关的激活过程的限制。在此，我们提出一种与焓无关的激活方法，该方法利用链置换作为通用框架来设计适体开关。我们通过数学和实验证明，这种方法在提高热稳定性方面非常有效，从而使适体开关具有更好的分析性能。通过对有效亲和力和动态范围进行细粒度和动态调节，以及构建类似于生物信号级联反应的合成DNA网络，也证明了可编程性得到了增强。我们的研究不仅丰富了当前用于工程设计和控制合成分子开关的工具箱，还为其热力学基础提供了新的见解，这对于各种合成生物学设计和应用至关重要。
