Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Angew Chem Int Ed Engl. 2020 Jun 22;59(26):10406-10410. doi: 10.1002/anie.202002020. Epub 2020 Apr 8.
Molecular recognition in cell biological process is characterized with specific locks-and-keys interactions between ligands and receptors, which are ubiquitously distributed on cell membrane with topological clustering. Few topologically-engineered ligand systems enable the exploration of the binding strength between ligand-receptor topological organization. Herein, we generate topologically controlled ligands by developing a family of tetrahedral DNA frameworks (TDFs), so the multiple ligands are stoichiometrically and topologically arranged. This topological control of multiple ligands changes the nature of the molecular recognition by inducing the receptor clustering, so the binding strength is significantly improved (ca. 10-fold). The precise engineering of topological complexes formed by the TDFs are readily translated into effective binding control for cell patterning and binding strength control of cells for cell sorting. This work paves the way for the development of versatile design of topological ligands.
细胞生物学过程中的分子识别具有配体和受体之间特定的锁钥相互作用的特点,这些配体和受体广泛分布在细胞膜上,并具有拓扑聚集性。少数拓扑工程化的配体系统能够探索配体-受体拓扑结构之间的结合强度。在这里,我们通过开发一系列四面体 DNA 框架(TDF)来生成拓扑控制的配体,从而使多个配体在化学计量和拓扑上得到有序排列。这种对多个配体的拓扑控制通过诱导受体聚集改变了分子识别的性质,从而显著提高了结合强度(约 10 倍)。通过 TDF 形成的拓扑复合物的精确工程设计可以很容易地转化为有效的细胞图案化结合控制和细胞分选的细胞结合强度控制。这项工作为开发多功能拓扑配体设计铺平了道路。