G-triplex (G3) structures formed with three consecutive G-tracts have recently been identified as a new emerging guanine-rich DNA fold. There could likely be a wide range of biological functions for G3s as occurring for G-quadruplex (G4) structures formed with four consecutive G-tracts. However, in comparison to the many reports on G4 nanoassemblies that organize monomers together in a controllable manner, G3-favored nanoassemblies have yet to be explored. In this work, we found that a natural alkaloid of sanguinarine can serve as a dynamic ligand glue to reversibly switch the dimeric nanoassemblies of the thrombin binding aptamer G3 (TBA-G3). The glue planarity was considered to be a crucial factor for realizing this switching. More importantly, external stimuli including pH, sulfite, O2 and H2 O2 can be employed as common regulators to easily modulate the glue's adhesivity for constructing and destructing the G3 nanoassemblies as a result of the ligand converting between isoforms. However, this assembly behavior does not occur with the counterpart TBA-G4. Our work demonstrates that higher-order G3 nanoassemblies can be reversibly operated by manipulating ligand adhesivity. This provides an alternative understanding of the unique behavior of guanine-rich sequences and focuses attention on the G3 fold since the nanoassembly event investigated herein might occur in living cells.
Keywords: G-quadruplexes; G-triplexes; biosensors; dimers; nanoassemblies.
© 2021 Wiley-VCH GmbH.