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Applications of guanine quartets in nanotechnology and chemical biology

This article has been updated


Guanine and related nucleobases such as guanosine, deoxyguanosine and isoguanosine are notable molecular tools for designing functional supramolecular assemblies. This popularity originates in their ability to self-assemble via a unique topological pluralism — as isolated nucleobases, discrete macrocyclic quartets and virtually infinite linear ribbons — that endows them with a considerable functional versatility. Many programmes have been launched to fine-tune the chemical properties of guanine derivatives, to make them usable under different experimental conditions, such as in organic or aqueous environments, and responsive to external stimuli, such as ionic strength, pH, light or temperature. These strategies aim to translate the chemical information encoded in a basic guanine unit into programmable, higher-order supramolecular architectures. Spectacular results have been recently obtained in various chemical fields, from supramolecular chemistry to chemical biology, from soft matter to catalysis. In this Review, we detail these advances and demonstrate how these multidisciplinary investigations cast a bright light on the diversity that guanines, synthetic guanines and related nucleobases uniquely offer in terms of both structure and function.

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Fig. 1: Timeline of the major steps in the discovery of DNA and G-quartets.
Fig. 2: LipoGs and their higher-order supramolecular assemblies.
Fig. 3: Tetrameric lipophilic guanosines assemblies.
Fig. 4: Structural studies of water-soluble G-assemblies.
Fig. 5: Applications of G-quartet-based devices as ionophores and ion channels.
Fig. 6: The nanotechnological applications of synthetic G-quartets-based nanostructures.
Fig. 7: DNAzyme-type catalysis performed by G-quartet molecular tools.
Fig. 8: Soft matter based on G-quartet molecular devices.
Fig. 9: Supramolecular hydrogels based on G-quartet assemblies.
Fig. 10: The chemical biology applications of SQ.

Change history

  • 11 November 2019

    This article has been corrected to add image credits to Figure 10. The permission line now reads Part b is adapted with permission from ref.147, CC-BY-4.0. Part c is adapted with permission from ref.148, OUP.


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L.S. and D.M. thank the Centre National de la Recherche Scientifique (CNRS) for funding. D.M. thanks the Agence Nationale de la Recherche (ANR-17-CE17-0010-01), the European Research Council (H2020-MSCA-IF-2016-750368), the Université de Bourgogne, Conseil Régional de Bourgogne (PARI) and the European Union (Pharmaco-imagerie et agents théranostiques, PO FEDER-FSE Bourgogne 2014–2020 programme) for financial support. The authors also thank their collaborators for the daily passionate scientific discussions and all scientists worldwide involved in the fascinating field of research, to make it lively, thrilling and always moving.

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the G4ome comprises all G-quadruplex (G4)-forming sequences identified in the genome (G4-DNA) and both the coding and non-coding transcriptome (G4-RNA).


lipophilic guanine derivatives aimed at being used in organic solvents, masking hydrophilic moieties (e.g. the hydroxyl groups of the guanosine’s ribose) through the use of aliphatic protecting groups.


3,3′-cyclic diguanylic acid discovered by Benziman and colleagues in 1987 (ref.151), originally as a regulator of cellulose production in bacteria and now known as a regulator of virulence factor production and biofilm formation.


low-molecular-weight molecules designed to interact specifically with DNA/RNA quadruplexes (G4s), mostly through π-stacking interactions with the G4’s accessible external quartets, but groove and loop binding has also been documented.

Fluorescence upconversion

this fluorescence spectroscopy (also known as sum frequency generation), is a nonlinear, high-resolution technique characterized by an emission wavelength that is shorter than the excitation wavelength.

Organic frameworks

three-dimensional organic structures in which building blocks are associated either through covalent bonds (covalent organic framework, or COF) or metal-mediated coordination (metal organic framework, or MOF).

Logic gates

in electronics, a logic gate is a device that performs a logical operation on one or two inputs and produces a single output. Logic gates are primarily implemented as switches of different possible natures (AND, OR, NOT, INHIBIT etc.) in digital circuits.

Lyotropic liquid crystal

property of an amphiphilic material (mesogen) that exhibits phase transitions upon dissolution in a suited solvent, in a concentration-dependent manner.

Storage moduli

indications of the ability of the gel to withstand and store deformation energy in an elastic manner, being dependent on its crosslinking state.


property of a material (gel, fluid), which is thick or viscous under static conditions, to become thin and liquid when shaken or sheared.

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Stefan, L., Monchaud, D. Applications of guanine quartets in nanotechnology and chemical biology. Nat Rev Chem 3, 650–668 (2019).

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