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

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

doi:10.1021/jm2000135

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

135 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	2196-2206
Number of pages	11
Journal	Journal of Medicinal Chemistry
Volume	54
Issue number	7
DOIs	https://doi.org/10.1021/jm2000135
Publication status	Published - 14-Apr-2011
Externally published	Yes

Keywords

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

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@article{72d42e8917ba425f968e6479ae5363c1,

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

abstract = "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.",

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

author = "Filipa Mendes and Michael Groessl and Nazarov, {Alexey A.} and Tsybin, {Yury O.} and Gianni Sava and Isabel Santos and Dyson, {Paul J.} and Angela Casini",

year = "2011",

month = apr,

day = "14",

doi = "10.1021/jm2000135",

language = "English",

volume = "54",

pages = "2196--2206",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "AMER CHEMICAL SOC",

number = "7",

}

TY - JOUR

T1 - Metal-based inhibition of poly(ADP-ribose) polymerase

T2 - The guardian angel of DNA

AU - Mendes, Filipa

AU - Groessl, Michael

AU - Nazarov, Alexey A.

AU - Tsybin, Yury O.

AU - Sava, Gianni

AU - Santos, Isabel

AU - Dyson, Paul J.

AU - Casini, Angela

PY - 2011/4/14

Y1 - 2011/4/14

N2 - 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.

AB - 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.

KW - ORGANOMETALLIC RUTHENIUM COMPOUND

KW - PLATINUM-MODIFIED DNA

KW - MASS-SPECTROMETRY

KW - ANTICANCER DRUGS

KW - SOLUTION CHEMISTRY

KW - NUCLEAR PROTEINS

KW - ZINC FINGERS

KW - GOLD(III) COMPLEXES

KW - BINDING PROPERTIES

KW - BIPYRIDYL LIGANDS

U2 - 10.1021/jm2000135

DO - 10.1021/jm2000135

M3 - Article

SN - 0022-2623

VL - 54

SP - 2196

EP - 2206

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 7

ER -

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

Abstract

Keywords

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