生体シグナルに応答して薬剤を放出するタンパク質被覆多孔質輸送体の開発

共价有机骨架（COFs）具有载药量大、功能可调等特点，是一种很有前途的药物载体。然而，由于药物在非靶组织中的渗漏导致副作用，因此需要位点选择性药物释放来制备理想的药物载体。因此，在本研究中，我们决定使用蛋白质作为门来实现药物的控制释放。具体而言，我们设计了一种生物粘附性COF（GST-COF）承载多个胍离子固定蛋白质。由于有许多类型的蛋白质响应于生物信号而经历结构转变，因此药物只能在靶组织中释放。选择钙调蛋白作为门，并通过钙离子引起的钙调蛋白构象变化来控制客体释放（Angew.化学成分：Int. Ed. 2021，60，8932-8937，被选为热门论文和封面）。这些实验结果表明，蛋白质构象的变化可以作为门的物质运输的可能性。已知许多蛋白质表现出与特定分子的高结合效率并在结合时引起构象变化。这一成果预计将有各种应用，如响应刺激释放药物。

Covalent organic frameworks (COFs) are promising candidate for drug carriers due to their large drug loading capacity and tunable functionality. However, site-selective drug release is required to make ideal drug carriers because leakage of drugs in non-target tissues leads to side effects. Therefore, in this study, we decided to use proteins as a gate to realize controlled drug release. Specifically, we design a bioadhesive COF (Glue-COF) bearing multiple guanidinium ion for immobilization of proteins. Since there are many types of proteins that undergoes a structural transition in response to biological signals, drug can be released at only target tissues. Calmodulin was chosen as a gate and controlled guest release through the conformational changes of calmodulin by calcium ions (Angew. Chem., Int. Ed. 2021, 60, 8932-8937, selected as a Hot Paper and Front Cover). These experimental results indicate the possibility that protein conformational changes can be used as gates for substance transportation. Many proteins are known to exhibit high binding efficiency to a specific molecule and cause a conformational change upon binding. This achievement is expected to have various applications such as the release of drugs in response to stimuli.