Baranda Pellejero Lorena, Nijenhuis Minke A D, Ricci Francesco, Gothelf Kurt V
Department of Chemistry, University of Rome, Tor Vergata, Via della Ricerca Scientifica, Rome, 00133, Italy.
Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, Aarhus, 8000, Denmark.
Small. 2023 Mar;19(13):e2200971. doi: 10.1002/smll.202200971. Epub 2022 Mar 28.
DNA-templated chemical reactions have found wide applications in drug discovery, programmed multistep synthesis, nucleic acid detection, and targeted drug delivery. The control of these reactions has, however, been limited to nucleic acid hybridization as a means to direct the proximity between reactants. In this work a system capable of translating protein-protein binding events into a DNA-templated reaction which leads to the covalent formation of a product is introduced. Protein-templated reactions by employing two DNA-antibody conjugates that are both able to recognize the same target protein and to colocalize a pair of reactant DNA strands able to undergo a click reaction are achieved. Two individual systems, each responsive to human serum albumin (HSA) and human IgG, are engineered and it is demonstrated that, while no reaction occurs in the absence of proteins, both protein-templated reactions can occur simultaneously in the same solution without any inter-system crosstalk.
DNA模板化化学反应已在药物发现、程序多步合成、核酸检测和靶向药物递送中得到广泛应用。然而，这些反应的控制仅限于核酸杂交，以此作为引导反应物之间接近程度的手段。在这项工作中，引入了一种能够将蛋白质-蛋白质结合事件转化为DNA模板化反应的系统，该反应会导致产物的共价形成。通过使用两种DNA-抗体缀合物实现了蛋白质模板化反应，这两种缀合物都能够识别相同的靶蛋白，并使一对能够进行点击反应的反应物DNA链共定位。构建了两个独立的系统，每个系统对人血清白蛋白（HSA）和人免疫球蛋白（IgG）有反应，结果表明，在没有蛋白质的情况下不发生反应，而两种蛋白质模板化反应可以在同一溶液中同时发生，且不存在任何系统间的串扰。
