MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, China.
Nat Commun. 2022 Oct 8;13(1):5936. doi: 10.1038/s41467-022-33738-3.
Dynamic regulation of nucleic acid hybridization is fundamental for switchable nanostructures and controllable functionalities of nucleic acids in both material developments and biological regulations. In this work, we report a ligand-invasion pathway to regulate DNA hybridization based on host-guest interactions. We propose a concept of recognition handle as the ligand binding site to disrupt Watson-Crick base pairs and induce the direct dissociation of DNA duplex structures. Taking cucurbit[7]uril as the invading ligand and its guest molecules that are integrated into the nucleobase as recognition handles, we successfully achieve orthogonal and reversible manipulation of DNA duplex dissociation and recovery. Moreover, we further apply this approach of ligand-controlled nucleic acid hybridization for functional regulations of both the RNA-cleaving DNAzyme in test tubes and the antisense oligonucleotide in living cells. This ligand-invasion strategy establishes a general pathway toward dynamic control of nucleic acid structures and functionalities by supramolecular interactions.
核酸杂交的动态调控对于核酸在材料发展和生物调控中的可切换纳米结构和可控功能至关重要。在这项工作中，我们报道了一种基于主客体相互作用的配体入侵途径来调节 DNA 杂交。我们提出了识别手柄的概念作为配体结合位点，以破坏 Watson-Crick 碱基对并诱导 DNA 双链结构的直接解离。以葫芦[7]脲作为入侵配体，其整合到核碱基中的客体分子作为识别手柄，我们成功地实现了 DNA 双链解离和恢复的正交和可逆操作。此外，我们进一步将这种配体控制的核酸杂交方法应用于试管中 RNA 切割 DNA 酶和活细胞中反义寡核苷酸的功能调控。这种配体入侵策略通过超分子相互作用为动态控制核酸结构和功能建立了一种通用途径。
