Optically Pure Metallohelices That Accumulate in Cell Nuclei, Condense/Aggregate DNA, and Inhibit Activities of DNA Processing Enzymes
Language English Country United States Media print-electronic
Document type Journal Article
- MeSH
- Cell Nucleus chemistry metabolism MeSH
- DNA Topoisomerases, Type I metabolism MeSH
- DNA antagonists & inhibitors genetics metabolism MeSH
- HCT116 Cells MeSH
- Topoisomerase I Inhibitors chemical synthesis chemistry pharmacology MeSH
- Humans MeSH
- Molecular Structure MeSH
- Optical Phenomena MeSH
- Ferrous Compounds chemical synthesis chemistry pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- DNA Topoisomerases, Type I MeSH
- DNA MeSH
- Topoisomerase I Inhibitors MeSH
- TOP1 protein, human MeSH Browser
- Ferrous Compounds MeSH
The water-compatible optically pure metallohelices made by self-assembly of simple nonpeptidic organic components around Fe(II) ions are now recognized as a distinct subclass of helicates that exhibit similar architecture to some natural cationic antimicrobial peptides. Notably, a new series of metallohelices was recently shown to exhibit biological activity, displaying high, structure-dependent activity against bacteria. It is also important that, thanks to their properties, such metallohelices can exhibit specific interactions with biomacromolecules. Here, following our prior report on the metallohelices that have high, structure-dependent activity against bacteria, we investigated the interactions of the series of iron(II) metallohelices with DNA, which is a potential pharmacological target of this class of coordination compounds. The results obtained with the aid of biophysical and molecular biology methods show that the investigated metallohelices accumulate in eukaryotic cells and that a significant fraction of the metallohelices accumulates in the cell nucleus, allowing them to interact also with nuclear DNA. Additionally, we have demonstrated that some metallohelices have a high affinity to DNA and are able to condense/aggregate DNA molecules more efficiently than conventional DNA-condensing agents, such as polyamines. Moreover, this capability of the metallohelices correlates with their efficiency to inhibit DNA-related enzymatic activities, such as those connected with DNA transcription, catalysis of DNA relaxation by DNA topoisomerase I, and cleavage by restriction enzymes.
Czech Academy of Sciences Institute of Biophysics Kralovopolska 135 CZ 61265 Brno Czech Republic
Department of Chemistry University of Warwick Gibbet Hill Road Coventry CV4 7AL United Kingdom
References provided by Crossref.org
Metallohelix vectors for efficient gene delivery via cationic DNA nanoparticles
