http://www.cnr.it/ontology/cnr/individuo/prodotto/ID293423
Electrospray ionization multi-stage mass spectrometric study of the interaction products of the cytotoxic complex [Cu(thp)4][PF6] with methionine-rich model peptides (Articolo in rivista)
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- Label
- Electrospray ionization multi-stage mass spectrometric study of the interaction products of the cytotoxic complex [Cu(thp)4][PF6] with methionine-rich model peptides (Articolo in rivista) (literal)
- Anno
- 2015-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1002/rcm.7100 (literal)
- Alternative label
Valentina Peruzzo, Francesco Tisato, Marina Porchia, Carlo Santini, Maura Pellei
and Piero Traldi (2015)
Electrospray ionization multi-stage mass spectrometric study of the interaction products of the cytotoxic complex [Cu(thp)4][PF6] with methionine-rich model peptides
in Rapid communications in mass spectrometry (Online); John Wiley & Sons Ltd., Chichester (Regno Unito)
(literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Valentina Peruzzo, Francesco Tisato, Marina Porchia, Carlo Santini, Maura Pellei
and Piero Traldi (literal)
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- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
- http://onlinelibrary.wiley.com/doi/10.1002/rcm.7100/pdf (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
- Rivista
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
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- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- 1-3,6 : CNR - IENI, Corso Stati Uniti 4, 35127 Padova, Italy /
4-5 : Scuola di Scienze e Tecnologie, Divisione di Chimica, Università di Camerino, Via S. Agostino 1, I 62032 Camerino, (MC), Italy (literal)
- Titolo
- Electrospray ionization multi-stage mass spectrometric study of the interaction products of the cytotoxic complex [Cu(thp)4][PF6] with methionine-rich model peptides (literal)
- Abstract
- RATIONALE: The cytotoxic activity of the copper(I) complex [Cu(thp)4][PF6] (CP) (thp = tris(hydroxymethyl) phosphine)
is correlated with its high accumulation in cancer cells. Human copper transporter 1 (hCtr1) has been described as the
main trans-membrane protein involved in cellular trafficking of physiological copper. Methionine-rich peptide sequences
incorporated in the extracellular domain of hCtr1 play a key role in the cellular internalization of copper. We wish to
investigate the interaction of CP with model peptides that mimic the extracellular domain of hCtr1.
METHODS: The interaction of CP with methionine-rich and methionine-free model peptides has been investigated by
electrospray ionization mass spectrometry and the interaction products have been characterized by multiple collisional
experiments, using an ion trap mass instrument.
RESULTS: The interaction of CP with selected methionine-rich model peptides, Ac-MMMMPMTFK-NH2 (P1) and AcMGMSYMDSK-NH2
(P2), shows that the native copper complex, after sequential loss of phosphines, induces the
formation of [Cu(P1)(thp)]+ and [Cu(P1/P2)]+ adducts reasonably by inclusion of the Cu(I) ion in the peptide framework.
Collisionally induced fragmentations (MSn) of [Cu(P1/P2)]+ give evidence that the metal is coordinated by the thioetherS
of two adjacent methionine residues. Interaction of the same peptides with the isostructural complex [Ag(thp)4]
+ or AgNO3 yields similar experimental evidence, leading to [Ag(P1/P2)]+.
CONCLUSIONS: Methionine sequences incorporated in model peptides are crucial for the recruitment of copper from
CP. Such a metal-peptide interaction does not take place when methionine-free Ac-NleGNleSYNleDSK-NH2 (P3) is
utilized. A mechanism for tumor cell internalization of CP involving: (i) chemically driven sequential loss of phosphines
from the native tetrahedral complex, followed by (ii) transfer of Cu(I) to the methionine-rich sequences typical of the
hCtr1 transporter, is proposed. Copyright © 2014 John Wiley & Sons, Ltd (literal)
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