Publication details

Naturally occurring quaternary benzo[c]phenanthridine alkaloids selectively stabilize G-quadruplexes

Authors

JAROŠOVÁ Petra PAROULEK Petr RÁJECKÝ Michal RÁJECKÁ Veronika TÁBORSKÁ Eva ERITJA R. AVINO A. MAZZINI S. GARGALLO R. TÁBORSKÝ Petr

Year of publication 2018
Type Article in Periodical
Magazine / Source Physical Chemistry Chemical Physics
MU Faculty or unit

Faculty of Science

Citation
Web http://pubs.rsc.org/en/Content/ArticleLanding/2018/CP/C8CP02681E#!divAbstract
Doi http://dx.doi.org/10.1039/c8cp02681e
Keywords HUMAN TELOMERIC DNA; ANTIPROLIFERATIVE ACTIVITY; PROMOTER REGION; SMALL MOLECULES; DRUG DESIGN; K+ SOLUTION; IN-VIVO; BINDING; BENZOPHENANTHRIDINE; OLIGONUCLEOTIDES
Description 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 T-m values (from 15 to 25 degrees 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.
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