Guided Assembly of Tetramolecular G-Quadruplexes

Abstract

Nucleic acids are finding applications in nanotechnology as nanomaterials, mechanical devices, templates, and biosensors. G-quadruplex DNA, formed by π-π stacking of guanine (G) quartets, is an attractive alternative to regular B-DNA because of the kinetic and thermodynamic stability of quadruplexes. However, they suffer from a fatal flaw: the rules of recognition, i.e., the formation of a G-quartet in which four identical bases are paired, prevent the controlled assembly between different strands, leading to complex mixtures. In this report, we present the solution to this recognition problem. The proposed design combines two DNA elements: parallel-stranded duplexes and a quadruplex core. Parallel-stranded duplexes direct controlled assembly of the quadruplex core, and their strands present convenient points of attachments for potential modifiers. The exceptional stability of the quadruplex core provides integrity to the entire structure, which could be used as a building block for nucleic acid-based nanomaterials. As a proof of principle for the design's versatility, we assembled quadruplex-based 1D structures and visualized them using atomic force and transmission electron microscopy. Our findings pave the way to broader utilization of G-quadruplex DNA in structural DNA nanomaterials.

Programmable i-motif DNA folding topology for a pH-switched reversible molecular sensing device

“…Since the i-motif core structure consists of two parallel C•C + base-paired duplexes, we primarily tested a few reverse Watson-Crick T•A base pairs that can stabilize parallel duplexes (27). A NMR study has demonstrated that an analogue U•A base pair is able to participate in and therefore extend the core of an intramolecular i-motif structure (32).…”

“…Therefore, the intermolecular assembly among different G-rich or C-rich strands cannot be easily controlled due to their self-association. To solve this difficulty, some antiparallel or parallel double-stranded handles have been employed for guided assembly of intermolecular G-quadruplexes (25–27). Alternatively, different i-motif-functionalized DNA units can be put into an interlocked structure where the unwanted interstructural association of bimolecular i-motifs is prevented (18).…”

Thioflavin T as a fluorescence light-up probe for G4 formation

“…These motifs are rare and A–T-rich; they would not have been suspected to form G4 base on primary sequence. Moreover, in the case of these particular sequences, another ligand named 9944, which has specificity for G4, also bound to PS1c (28) and triplexes. One should also note that the thresholds we chose for the fluorescence enhancement cutoff will depend on the experimental settings and instrumental response; one should include a few positive and negative controls in each experiment.…”

Orienting Tetramolecular G‐Quadruplex Formation: The Quest for the Elusive RNA Antiparallel Quadruplex

“…This effect induces the synapse formation of quadruplex structures through duplex formation. [21,22] The understanding of a quadruplex-duplex switch in these supramolecular structures in addition to the control of the strand association during the assembly process could be applied for the construction of nanoparticles and devices.…”