RNA G-quadruplexes have been suggested to play key roles in fundamental biological processes and are linked to human diseases. Thus, they also represent good potential therapeutic targets. Here, we describe, using the methods of molecular biophysics, interactions of a series of biologically-active supramolecular cationic metallohelices with human telomeric RNA G-quadruplex. We demonstrate that the investigated metallohelices bind with a high affinity to human telomeric RNA G-quadruplex and that their binding selectivity considerably differs depending on the dimensions and overall shape of the metallohelices. Additionally, the investigated metallohelices inhibit DNA synthesis on the RNA template containing four repeats of the human telomeric sequence by stabilizing the RNA G-quadruplex structure. Collectively, the results of this study suggest that stabilization of RNA sequences capable of G-quadruplex formation by metallohelices investigated in this work might contribute to the mechanism of their biological activity.

Department of Chemistry University of Warwick Gibbet Hill Road Coventry CV4 7AL UK

Institute of Biophysics Czech Academy of Sciences Kralovopolska 135 61265 Brno Czech Republic

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