Quadruplexes are everywhere!
A number of non-classical pairing patterns are possible between or within DNA and RNA strands. These interactions result in the formation of unusual structures, among them G-quadruplexes and i-motifs. 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. G-quadruplexes can find applications in biology, medicine, as well as biotech- and nano-technologies 1. We are developping tools to understand their folding and polymorphism 2. In parallel, we proposed a new algorithm for prediction of G4 propensity of unprecedented accuracy 3. We are now applying this G4-Hunter prediction tool to a number of genomes. In humans, we showed an association of G4-prone motifs with origins of replication 4. We also became interested in quadruplexes quadruplex-prone regions conserved in the genome of a number of prokaryotes, Archaea, viruses (HIV, HCV 5, Ebola 6…) and in "G4-poor" model organism such as Dictyostelium discoideum or Plasmodium falciparum to confirm the importance of G-quadruplexes in biology 7. In addition, we are investigating new families of G4 ligands (G4L), either as fluorescent light-up probes 8, anti-allergic 9 or anti-parasitic 10 drugs.
(1) Mergny & Sen, Chem. Rev. 2019, 119: 6290-6325.
(2) Cheng et al, Nucleic Acids Res. 2018, 46: 9264; Cheng et al, in preparation.
(3) Bedrat et al, Nucleic Acids Res. 2016, 44: 1746; Brazda et al, Bioinformatics. 2019, in press. doi: 10.1093/bioinformatics/btz087.
(4) Prorok et al, Nature Com. 2019, 10(1): 3274
(5) Jaubert et al, Sci Adv. 2018, 8: 8120.
(6) Amrane, Bedrat & Mergny. Methods and pharmaceutical compositions for the treatment of filovirus infection. Patent EP15305367.
(7) Guédin et al, Nucleic Acids Res. 2018, 46: 5297; Saad et al, Nucleic Acids Res. 2019, 47: 4363-4374 ; Ganazion et al, submitted.
(8) Zuffo et al, Nucleic Acids Res. 2018, 46: e115.
(9) Dalloul et al, J. Allergy Clin Immunol. 2018, 142: 1352
(10) Belmonte-Reche et al, J. Med. Chem. 2018, 61: 1231; Guillon et al, Chem. Biol. Drug Des. 2018, 91: 974. Zuffo et al. Eur. J. Med. Chem. 2019, 163: 54-66.
Domain 1 - UMR 9187 / U1196 - Chemistry, Modelling and Imaging for Biology