DNA interactions of monofunctional organometallic ruthenium(II) antitumor complexes in cell-free media
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
PubMed
14516206
DOI
10.1021/bi034933u
Knihovny.cz E-zdroje
- MeSH
- benzenové deriváty chemie metabolismus MeSH
- denaturace nukleových kyselin MeSH
- DNA řízené RNA-polymerasy antagonisté a inhibitory genetika metabolismus MeSH
- DNA chemie účinky léků metabolismus MeSH
- konformace nukleové kyseliny MeSH
- molekulární sekvence - údaje MeSH
- organokovové sloučeniny chemie metabolismus farmakologie MeSH
- organoplatinové sloučeniny chemie farmakologie MeSH
- plazmidy chemie genetika MeSH
- polydeoxyribonukleotidy chemie metabolismus MeSH
- protinádorové látky chemie metabolismus farmakologie MeSH
- RNA antagonisté a inhibitory biosyntéza MeSH
- ruthenium chemie metabolismus farmakologie MeSH
- sekvence nukleotidů MeSH
- skot MeSH
- teplota MeSH
- virové proteiny MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- bacteriophage T7 RNA polymerase MeSH Prohlížeč
- benzenové deriváty MeSH
- calf thymus DNA MeSH Prohlížeč
- DNA řízené RNA-polymerasy MeSH
- DNA MeSH
- organokovové sloučeniny MeSH
- organoplatinové sloučeniny MeSH
- polydeoxyribonukleotidy MeSH
- protinádorové látky MeSH
- RNA polymerase SP6 MeSH Prohlížeč
- RNA MeSH
- ruthenium MeSH
- virové proteiny MeSH
Modifications of natural DNA in a cell-free medium by antitumor monodentate Ru(II) arene compounds of the general formula [(eta(6)-arene)Ru(en)Cl](+) (arene = biphenyl, dihydroanthracene, tetrahydroanthracene, p-cymene, or benzene; en = ethylenediamine) were studied by atomic absorption, melting behavior, transcription mapping, circular and linear dichroism, plasmid unwinding, competitive ethidium displacement, and differential pulse polarography. The results indicate that these complexes bind preferentially to guanine residues in double-helical DNA. The data are consistent with DNA binding of the complexes containing biphenyl, dihydroanthracene, or tetrahydroanthracene ligands that involves combined coordination to G N7 and noncovalent, hydrophobic interactions between the arene ligand and DNA, which may include arene intercalation and minor groove binding. In contrast, the single hydrocarbon rings in the p-cymene and benzene ruthenium complexes cannot interact with double-helical DNA by intercalation. Interestingly, the adducts of the complex containing p-cymene ligand, which has methyl and isopropyl substituents, distort the conformation and thermally destabilize double-helical DNA distinctly more than the adducts of the three multiring ruthenium arene compounds. It has been suggested that the different character of conformational alterations induced in DNA, and the resulting thermal destabilization, may affect differently further "downstream" effects of damaged DNA and consequently may result in different biological effects of this new class of metal-based antitumor compounds. The results point to a unique profile of DNA binding for Ru(II) arene compounds, suggesting that a search for new anticancer compounds based on this class of complexes may also lead to an altered profile of biological activity in comparison with that of metal-based antitumor drugs already used in the clinic or currently on clinical trials.
Citace poskytuje Crossref.org
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