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聽鈥淒NA comes in many forms鈥� (A. Rich): a number of non-classical pairing patterns are possible between or within DNA strands. These interactions result in the formation of unusual structures, among them the G-quadruplex and the i-motif. G-quadruplexes (G4) result from the stacking of several G-quartets (formed by hydrogen bonding of four coplanar guanines), and are stabilized by monocations such as sodium and potassium. These structures are very stable under physiological conditions but were first thought to be an in vitro anomaly. Critical evidence for the biological relevance of G4 has come from use of G4-specific antibodies and results obtained in a variety of organisms. We are now using novel strategies, including new analytical tools and a unique model organism, to confirm the importance of G-quadruplexes and study their properties. We first developed a new algorithm for prediction of G4 propensity (1). We developed new assays to identify and analyze selective G4 ligands (2,3). We provide evidence for G4 existence in living cells using in vivo NMR (4). Having established that quadruplex-prone regions are conserved in the genome of viruses, we are currently investigating whether quadruplexes may become the Achilles' Heel of the viral life cycle (5,6).

In addition, besides their importance in Biology, unusual nucleic acid structures may find applications in Biotechnologies and Nanotechnologies. These structures create a greater diversity of DNA-based building blocks for nanomaterials and have clear advantages over conventional duplex DNA, such as enhanced thermal stability, conductivity, and sensitivity to chemical stimuli (for a review: (7)). A major drawback of G4 and i-DNA designs is the lack of control over the assembly process due to a homo-recognition problem: as G-quartets are formed from four identical bases, a guanine from one G-rich strand can bond with its own strand or with another strand at any of the guanines. We recently provided solutions to this problem, using either parallel-stranded (8) or canonical antiparallel (9, 10) DNA duplexes to direct the controlled assembly of G4 structures and i-motifs. Finally, we recently demonstrated that G-rich DNA sequences may function as a double switch whose function is based on different triggers provided that their secondary structures and stability display a high dependence on cation nature and concentration (11).

(1) Bedrat et al., Nucleic Acids Res. 2016, 44: 1746

(2) Mendoza et al., Nucleic Acids Res. 2015, 43: e71

(3) De Rache et al., Biochimie 2015, 115: 194

(4) Salgado et al., Chem. Sci. 2015, 6: 3273

(5) Amrane et al., J. Am. Chem. Soc 2014, 136: 5249

(6) M茅tifiot et al., Biochimie 2015, 118: 173

(7) Yatsunyk, Mendoza & Mergny., Acc. Chem. Res. 2014, 47: 1836

(8) Yatsunyk et al, ACS Nano 2013, 7: 5701

(9) Mendoza et al., Chem. Eur. J. 2015, 21: 6732

(10) Fu et al., 2016, in preparation

(11) Largy et al., J. Am. Chem. Soc. 2016, 138: 2780