Lanphere Conor, Arnott Patrick M, Jones Sioned Fôn, Korlova Katarina, Howorka Stefan
Department of Chemistry Institute of Structural and Molecular Biology University College London London WC1H 0AJ UK.
Department of Biochemical Engineering University College London London WC1E 7JE UK.
Angew Chem Weinheim Bergstr Ger. 2021 Jan 25;133(4):1931-1936. doi: 10.1002/ange.202011583. Epub 2020 Nov 24.
Chemistry is ideally placed to replicate biomolecular structures with tuneable building materials. Of particular interest are molecular nanopores, which transport cargo across membranes, as in DNA sequencing. Advanced nanopores control transport in response to triggers, but this cannot be easily replicated with biogenic proteins. Here we use DNA nanotechnology to build a synthetic molecular gate that opens in response to a specific protein. The gate self-assembles from six DNA strands to form a bilayer-spanning pore, and a lid strand comprising a protein-binding DNA aptamer to block the channel entrance. Addition of the trigger protein, thrombin, selectively opens the gate and enables a 330-fold increase inw the transport rate of small-molecule cargo. The molecular gate incorporates in delivery vesicles to controllably release enclosed cytotoxic drugs and kill eukaryotic cells. The generically designed gate may be applied in biomedicine, biosensing or for building synthetic cells.
化学在利用可调节的建筑材料复制生物分子结构方面具有理想的条件。特别令人感兴趣的是分子纳米孔，它能像在DNA测序中那样跨膜运输物质。先进的纳米孔能响应触发因素来控制运输，但这很难用生物源蛋白质复制。在这里，我们利用DNA纳米技术构建了一种能响应特定蛋白质而打开的合成分子门。该门由六条DNA链自组装形成一个跨双层的孔，还有一条包含与蛋白质结合的DNA适配体的盖链来阻断通道入口。添加触发蛋白凝血酶可选择性地打开门，使小分子物质的运输速率提高330倍。这种分子门可整合到递送囊泡中，以可控方式释放包裹的细胞毒性药物并杀死真核细胞。这种经过通用设计的门可应用于生物医学、生物传感或用于构建合成细胞。
