Cationic FeII Triplex-Forming Metallohelices as DNA Bulge Binders.

Ondrej Hrabina, Jaroslav Malina, Peter Scott, Viktor Brabec

Chemistry (Weinheim an der Bergstrasse, Germany) 2020 Dec 09

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Bulges are essential structural elements in nucleic acids. The detection and targeting of bulged DNA sequences are highly important. Small molecules capable of targeting DNA bulges have attracted considerable attention because they cannot only be used as reagents for bulge recognition, but also as potential therapeutic drugs. Herein, the interactions of DNA duplexes, containing bulges of various sizes and base compositions, with a series of FeII triplex-forming metallohelices are reported. The results obtained, with the aid of molecular biophysics methods, show that the investigated metallohelices prefer to bind to bulged DNA, rather than double-stranded DNA, and that their binding affinities towards bulges differ among individual metallohelices. Moreover, their binding affinities towards bulges strongly depend on the bulge size and the base composition of the bulge loop. The investigated metallohelices can enter eukaryotic cells and accumulate in the cell nucleus, allowing them to interact with nucleic acids. Hence, it is reasonable to suggest that the interaction of metallohelices with nucleic acid bulges might contribute to the mechanism of their biological activity. © 2020 Wiley-VCH GmbH.

Citation

Ondrej Hrabina, Jaroslav Malina, Peter Scott, Viktor Brabec. Cationic FeII Triplex-Forming Metallohelices as DNA Bulge Binders. Chemistry (Weinheim an der Bergstrasse, Germany). 2020 Dec 09;26(69):16554-16562