Conformation of DNA modified by monofunctional Ru(II) arene complexes: recognition by DNA binding proteins and repair. Relationship to cytotoxicity
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
15664521
DOI
10.1016/j.chembiol.2004.11.008
PII: S1074-5521(04)00328-X
Knihovny.cz E-resources
- MeSH
- DNA-Directed RNA Polymerases chemistry drug effects MeSH
- DNA chemistry drug effects MeSH
- Calorimetry MeSH
- Nucleic Acid Conformation * drug effects MeSH
- Humans MeSH
- Molecular Sequence Data MeSH
- DNA Repair drug effects MeSH
- Organometallic Compounds chemistry pharmacology MeSH
- Ruthenium chemistry MeSH
- Base Sequence MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA-Directed RNA Polymerases MeSH
- DNA MeSH
- Organometallic Compounds MeSH
- Ruthenium MeSH
We analyzed DNA duplexes modified at central guanine residues by monofunctional Ru(II) arene complexes [(eta(6)-arene)Ru(II)(en)(Cl)](+) (arene = tetrahydroanthracene or p-cymene, Ru-THA or Ru-CYM, respectively). These two complexes were chosen as representatives of two different classes of Ru(II) arene compounds for which initial studies revealed different binding modes: one that may involve DNA intercalation (tricyclic-ring Ru-THA) and the other (mono-ring Ru-CYM) that may not. Ru-THA is approximately 20 times more toxic to cancer cells than Ru-CYM. The adducts of Ru-THA and Ru-CYM have contrasting effects on the conformation, thermodynamic stability, and polymerization of DNA in vitro. In addition, the adducts of Ru-CYM are removed from DNA more efficiently than those of Ru-THA. Interestingly, the mammalian nucleotide excision repair system has low efficiency for excision of ruthenium adducts compared to cisplatin intrastrand crosslinks.
References provided by Crossref.org
Biophysical studies on the stability of DNA intrastrand cross-links of transplatin
