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Phenoxazine-based scaffold for designing G4-interacting agents.

Vladimir B TsvetkovAnna M VarizhukSofia A LizunovaTatiana A NikolenkoIgor A IvanovVjacheslav V SeverovEvgeny S BelyaevEgor A ShitikovGalina E PozmogovaMikhail S Baranov
Published in: Organic & biomolecular chemistry (2022)
G-quadruplexes (G4) represent one class of non-canonical secondary nucleic acid structures that are currently regarded as promising and attractive targets for anti-cancer, anti-viral and antibacterial therapy. Herein, we probe a new i-clamp-inspired phenoxazine scaffold for designing G4-stabilizing ligands. The length of the protonated aminoalkyl tethers ('arms') of the phenoxazine-based ligand was optimized in silico. Two double-armed ligands differing in the relative orientation of their arms and one single-armed ligand were synthesized. The two-armed ligands significantly enhanced the thermal stability of the G-quadruplex structures (increasing the melting temperature by up to 20 °C) and displayed G4 selectivity over duplex DNA. The ligands look promising for biological studies and the phenoxazine scaffold could be a starting point for designing new G4-interacting compounds.
Keyphrases
  • nucleic acid
  • high resolution
  • tissue engineering
  • quantum dots
  • stem cells
  • cell free
  • living cells
  • single molecule
  • bone marrow
  • silver nanoparticles
  • molecular dynamics simulations
  • fluorescent probe