Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 14, Issue 33, Pages 10408-10414Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.200801364
Keywords
DNA cleavage; DNA unwinding; helical structures; ruthenium; supramolecular chemistry
Categories
Funding
- Academy of Sciences of the Czech Republic [B400040601, IAA400040803, IQS500040581, KAN200200651, AV0Z50040507, AV0Z50040702]
- Ministry of Education of the Czech Republic [MSMT LC06030, ME08017]
- Ministry of Health of the CR [NR8562-4/2005]
- COST D39 [WGs D39/002/07, D39/004/06]
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Metallosupramolecular chemistry was used to design a new class of synthetic agents, namely, tetracationic supramolecular cylinders, that bind strongly and noncovalently in the major groove of DNA. To gain additional information on interactions of the cylinders with DNA we explored DNA unwinding and sequence-specific binding properties, as well as DNA photonuclease activity of ruthenium(II) metallosupramolecular cylinder [Ru2L3](4+), where L is a bis-pyridylimine ligand. We found that [Ru2L3](4+) unwinds negatively supercoiled plasmid DNA and exhibits binding preference to regular alternating purine-pyrimidine sequences in a similar way to the [Fe2L3](4+) analogue. Photocleavage studies showed that, unlike [Fe2L3](4+), [Ru2L3](4+) induces single-strand breaks on irradiation by visible and UVA light and cleaves DNA mainly at guanine residues contained preferentially in regularly alternating purine-pyrimidine nucleotides. As [Ru2L3](4+) binds and cleaves DNA in a sequence-dependent manner, it may provide a useful tool for basic and applied biology, such as for controlled manipulation of the genome.
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