Title
Naturally occurring quaternary benzo[c]phenanthridine alkaloids selectively stabilize G-quadruplexes
Author
Petra Jarosova, Petr Paroulek, Michal Rajecky, Veronika Rajecka, Eva Taborska, Ramon Eritja, Anna Aviñó, Stefania Mazzini, Raimundo Gargallo, Petr Taborsky
Year
2018
Journal
Physical Chemistry Chemical Physics
Abstract
In this work, the interaction of six natural benzo[c]phenanthridine alkaloids (macarpine, sanguilutine, sanguirubine, chelerythrine, sanguinarine and chelirubine) with parallel and antiparallel G-quadruplex DNA structures was studied. HT22 corresponding to the end of human telomeres and the modified promoter oncogene c-kit21 and Pu22 sequences have been used. Spectroscopically-monitored melting experiments and fluorescence titrations, competitive dialysis and nuclear magnetic resonance spectroscopy were used for this purpose. The results showed that these alkaloids stabilized G-quadruplex structures in terms of increments of Tm values (from 15 to 25 °C) with high selectivity over duplexes and unfolded DNA. The mode of binding was mainly by stacking on the terminal G-tetrads with stoichiometries of 1 : 2 (DNA : ligand). The presence of non-specific electrostatic interactions was also observed. Overall, the results pointed to a strong stabilization of G-quadruplex structures by these alkaloids.
Instrument
J-810
Keywords
Circular dichroism, DNA structure, Thermal stability, Thermodynamics, Ligand binding, Biochemistry