DOI: 10.1002/chem.201300791 Multitasking Water-Soluble Synthetic G-Quartets: From Preferential RNA– Quadruplex Interaction to Biocatalytic Activity Romain Haudecoeur, Loic Stefan, and David Monchaud* [a] Introduction Guanine (G) is a fascinating nucleobase thanks to its highly versatile hydrogen-bond-creating capability, which makes it suitable for participating to higher-order supramolecular as- semblies. [1] The nature of these suprastructures depends mainly on the experimental conditions: guanines can be in- volved either in GC base pairs, under standard Watson– Crick conditions, in G-quartets, a cyclic array of four gua- nines held together by Watson–Crick/Hoogsteen H-bonds, mostly found in cation-rich water solutions, [2] or in G-rib- bons, a linear and virtually infinite ribbon-like arrangement, mostly formed at elevated concentrations in cation-less or- ganic solvent. [3] Naturally occurring G-quartets have attracted recently an intensified interest for their ability to be formed intramolec- ularly in G-rich DNA and RNA sequences. [4] These G-rich DNA or RNA stretches thus give rise to corresponding G- quadruplex structures, whose stability results from the self- stacking of contiguous G-quartets. The discovery of quadru- plex-forming sequences in key regions of the chromosomes (telomere, [5] promoter region of oncogenes) [6] or mRNA [7] thus spurred investigations into the possibility of controlling the corresponding cellular events (chromosomal stability, regulation of gene expression at transcriptional (DNA quad- ruplexes) or translational level (RNA quadruplexes), etc.) [8] by the stabilization of the G-quadruplexes with small mole- cules (so-called G-quadruplex ligands, currently considered as promising anti-cancer agents). [9] Non-naturally occurring G-quartets, also known as syn- thetic G-quartets (SQ), have been also intensively studied, mostly for bionanotechnological applications that include their use as building blocks for stable [10] and dynamic hydro- gels, [11] for nanoscale objects (including organic nanoparti- cles, [12] nanoparticle assemblies, [13] and biomolecular nano- wires) [14] or for self-organized surfaces. [15] SQ have been also studied for their nanotool-like properties (notably as artifi- cial ion channels [16] and ion extractants). [17] In sharp contrast, intramolecular synthetic G-quartets (iSQ) have been more sparingly studied. In a vast majority of the aforementioned examples, guanines are used as monomers, thereby enabling the formation of intermolecular G-quartets only. Strategies have been devised to favor the tetramolecular assembly, through the use for example of lipophilic G-conACHTUNGTRENNUNGju- ACHTUNGTRENNUNGgates. [16b,c, 18] However, one elegant way to promote such a formation is to assemble more than one guanine in a single scaffold: when two G units are linked together, through PEG, [11, 15a] biphenylene, [19] bis-lithocholate [20] or cyclic bis- phosphate linkers, [21] the corresponding G-dimers promote the formation of supramolecular assemblies like tunable sol- gel phase, [11] membrane films, [15a] barrel-type [19] and guano- sine-sterol artificial ion channels [20] or synthetic G-quadru- Abstract: Natural G-quartets, a cyclic and coplanar array of four guanine res- idues held together through a Watson– Crick/Hoogsteen hydrogen-bond net- work, have received recently much at- tention due to their involvement in G- quadruplex DNA, an alternative higher-order DNA structure strongly suspected to play important roles in key cellular events. Besides this, syn- thetic G-quartets (SQ), which artificial- ly mimic native G-quartets, have also been widely studied for their involve- ment in nanotechnological applications (i.e., nanowires, artificial ion channels, etc.). In contrast, intramolecular syn- thetic G-quartets (iSQ), also named template-assembled synthetic G-quar- tets (TASQ), have been more sparingly investigated, despite a technological potential just as interesting. Herein, we report on a particular iSQ named PNA DOTASQ, which demonstrates very interesting properties in terms of DNA and RNA interaction (notably its selec- tive recognition of quadruplexes ac- cording to a bioinspired process) and catalytic activities, through its ability to perform peroxidase-like hemin-mediat- ed oxidations either in an autonomous fashion (i.e., as pre-catalyst for TASQ- zyme reactions) or in conjunction with quadruplex DNA (i.e., as enhancing agents for DNAzyme processes). These results provide a solid scientific basis for TASQ to be used as multitasking tools for bionanotechnological applica- tions. Keywords: DNA · G-quadruplexes · G-quartets · RNA · supramolecular chemistry [a] Dr. R. Haudecoeur, L. Stefan, Dr. D. Monchaud Institut de Chimie MolØculaire de l)UniversitØ de Bourgogne ICMUB CNRS UMR6302, 9, Avenue Alain Savary 21000 Dijon (France) Fax: (+ 33) 380-396-117 E-mail : david.monchaud@u-bourgogne.fr Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201300791. Chem. Eur. J. 2013, 19, 12739 – 12747 # 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 12739 FULL PAPER