Spectroscopy and calorimetry evidence of binding-induced thermal stabilization of human telomeric G-quadruplex DNA by 1,5-disubstituted morpholino-amido anthraquinone: Molecular basis of anticancer action

We report interaction of 1,5-Bis (3-morpholinopropionamido) anthracene-9,10-dione with Human Telomeric G4 DNA sequences, wHTel26 and HTel22 in presence of K+ and Na+ ions, respectively. Surface Plasmon Resonance yields association constant K-b = 1.0-3.8x10(5) M-1 with HTel22 in K+-rich solution. Significant hypochromism (46-79 %) and fluorescence quenching (83-92 %), no change in absorption and emission maxima, unaltered fluorescence lifetime of ligand, change in conformation of G4 DNA with no overall disruption of G-quartets and absence of induced Circular Dichroism band, suggest external groove binding of ligand. Molecular docking shows short contacts of 9O, 15N, 18O, 11NH, 12CO atoms of ligand with A3, G4, G22, G23 and A1, G3, G14 bases of 3 + 1 hybrid-2 and 2 + 2 anti-parallel conformers, respectively without making any contact with loops, to an energetically more favourable conformation. Ligand-influenced thermal stabilization, up to Delta T-m = 37/48 degrees C, may disrupt access of telomerase enzyme to telomere and promote apoptosis in malignant tissues.