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

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

Druh Článek v odborném periodiku
Časopis / Zdroj Physical Chemistry Chemical Physics
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www http://pubs.rsc.org/en/Content/ArticleLanding/2018/CP/C8CP02681E#!divAbstract
Doi http://dx.doi.org/10.1039/c8cp02681e
Klíčová slova HUMAN TELOMERIC DNA; ANTIPROLIFERATIVE ACTIVITY; PROMOTER REGION; SMALL MOLECULES; DRUG DESIGN; K+ SOLUTION; IN-VIVO; BINDING; BENZOPHENANTHRIDINE; OLIGONUCLEOTIDES
Popis 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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