Host–Guest Tethered DNA Transducer: ATP Fueled Release of a Protein Inhibitor from Cucurbit[7]uril,Journal of the American Chemical Society

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Host–Guest Tethered DNA Transducer: ATP Fueled Release of a Protein Inhibitor from Cucurbit[7]uril
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2017-09-20 00:00:00 , DOI: 10.1021/jacs.7b07977
Xiao Zhou ₁ , Xiaoye Su ₁ , Pravin Pathak ₁ , Ryan Vik ₁ , Brittany Vinciguerra ₂ , Lyle Isaacs ₂ , Janarthanan Jayawickramarajah ₁

Affiliation

Host–guest complexes are emerging as powerful components in functional systems with applications ranging from materials to biomedicine. In particular, CB7 based host–guest complexes have received much attention for the controlled release of drugs due to the remarkable ability of CB7 toward binding input molecules in water with high affinity leading to displacement of CB7 from included pharmacophores (or from drug loaded porous particles). However, the release of bound guests from CB7 in response to endogenous biological molecules remains limited since the input biomolecule needs to have the appropriate chemical structure to bind tightly into the CB7 cavity. Herein we describe a synthetic transducer based on self-assembling DNA–small molecule chimeras (DCs) that is capable of converting a chosen biological input, adenosine triphosphate (ATP; that does not directly bind to the CB7 host), into functional displacement of a protein inhibitor that is bound within the CB7 host. Our system—which features the first example of a covalent CB-DNA conjugate—is highly modular and can be adapted to enable responsiveness to other biologically/clinically relevant stimuli via its split DNA aptamer architecture.

中文翻译：

主持人-客人拴系的DNA换能器：ATP促进了葫芦丝蛋白抑制剂的释放[7] uril

主客体复合物正在成为功能系统中的强大组件，其应用范围从材料到生物医学。尤其是，基于CB7的宿主-客体复合物在药物的控制释放方面受到了广泛关注，因为CB7能够以高亲和力结合水中的输入分子，从而导致CB7从包含的药效团（或载药的多孔颗粒）中置换出来。）。然而，由于输入的生物分子需要具有适当的化学结构以紧密结合到CB7腔中，因此响应于内源性生物分子而从CB7释放结合的客人仍然受到限制。本文中，我们描述了一种基于自组装DNA小分子嵌合体（DC）的合成换能器，它能够转换选定的生物输入，三磷酸腺苷（ATP; （不直接与CB7宿主结合）的蛋白质转移到结合在CB7宿主内的蛋白质抑制剂的功能上。我们的系统（具有共价CB-DNA共轭物的第一个例子）是高度模块化的，可通过其分离的DNA适体结构进行调整，以使其对其他生物学/临床相关刺激具有响应性。

更新日期：2017-09-20

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