Publication

Metal-based inhibition of poly(ADP-ribose) polymerase: The guardian angel of DNA

Mendes, F., Groessl, M., Nazarov, A. A., Tsybin, Y. O., Sava, G., Santos, I., Dyson, P. J. & Casini, A., 14-Apr-2011, In : Journal of Medicinal Chemistry. 54, 7, p. 2196-2206 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Filipa Mendes
  • Michael Groessl
  • Alexey A. Nazarov
  • Yury O. Tsybin
  • Gianni Sava
  • Isabel Santos
  • Paul J. Dyson
  • Angela Casini

The inhibition activity of a series of anticancer metal complexes based on platinum, ruthenium, and gold metal ions was evaluated on the zinc-finger protein PARP-1, either purified or directly on protein extracts from human breast cancer MCF7 cells. Information on the reactivity of the metal complexes with the PARP-1 zinc-finger domain was obtained by high-resolution ESI FT-ICR mass spectrometry. An excellent correlation between PARP-1 inhibition in protein extracts and the ability of the complexes to bind to the zinc-finger motif (in competition with zinc) was established. The results support a model whereby displacement of zinc from the PARP-1 zinc finger by other metal ions leads to decreased PARP-1 activity. In vitro combination studies of cisplatin with NAMI-A and RAPTA-T on different cancer cell lines (MCF7, A2780, and A2780cisR) showed that, in some cases, a synergistic effect is in operation.

Original languageEnglish
Pages (from-to)2196-2206
Number of pages11
JournalJournal of Medicinal Chemistry
Volume54
Issue number7
Publication statusPublished - 14-Apr-2011
Externally publishedYes

    Keywords

  • ORGANOMETALLIC RUTHENIUM COMPOUND, PLATINUM-MODIFIED DNA, MASS-SPECTROMETRY, ANTICANCER DRUGS, SOLUTION CHEMISTRY, NUCLEAR PROTEINS, ZINC FINGERS, GOLD(III) COMPLEXES, BINDING PROPERTIES, BIPYRIDYL LIGANDS

ID: 12746546