Ultrastable Bimolecular G‑Quadruplexes Programmed DNA Nanoassemblies for Reconfigurable Biomimetic DNAzymes

• Published in: ACS nano Vol. 13; no. 10; pp. 11947 - 11954
• Main Authors: Zheng, Jiao, Du, Yi, Wang, Huihui, Peng, Pai, Shi, Lili, Li, Tao
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 22.10.2019
• Subjects: biomimetic DNAzyme; programmable DNA assembly; framework nucleic acid; human telomerase; bimolecular G-quadruplex
• ISSN: 1936-0851; 1936-086X; 1936-086X
• DOI: 10.1021/acsnano.9b06029

The relatively low stability and polymorphism of bimolecular G-quadruplexes (bi-G4s) are big difficulties that are faced in employing them to guide DNA assembly, as they are usually subject to a transformation into more stable tetramolecular or G-wire structures favored by K+ or Mg2+. Although bi-G4s benefit by additional duplex handles, a challenge remains in tailoring their intrinsic properties to resolve the above difficulties. Toward this challenge, here we engineer several ultrastable bi-G4s via replacing their nucleotide loops with special mini-hairpins, which consist of a GAA loop and a short GC-paired stem. Such a structural alteration favors the formation of G:C:G:C tetrads in the head-to-head folding topologies of bi-G4s and improves their thermal stability, with an increase in the melting temperature by up to 25 °C. It dramatically reduces their structural conversion into G-wires, verified by atomic force microscopy. These features enable the utilization of two well-chosen bi-G4s to shape a DNA nanotriangle into the desired framework nucleic acid (FNA) architectures such as “bowknot” and “butterfly” that are reversibly switched by the bi-G4s. On this basis, we further build a reconfigurable DNAzyme device to mimic the activation of human telomerase that is modulated by the G4 dimerization. Our designed ultrastable bi-G4s will offer a promising tool for dynamically manipulating intracellular DNA nanoassemblies with endogenous K+ and exploring the relationship between dimerization and function in some physiological processes.