2007
DOI: 10.1021/bi701516q
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Insights into the Molecular Mechanisms of Protein Platination from a Case Study:  The Reaction of Anticancer Platinum(II) Iminoethers with Horse Heart Cytochrome c

Abstract: The interactions of anticancer metallodrugs with proteins are attracting a growing interest in the current literature because of their relevant pharmacological and toxicological consequences. To understand in more depth the nature of those interactions, we have investigated the reactions of four anticancer platinum(II) iminoether complexes, namely, trans- and cis-EE (trans- and cis-[PtCl2{(E)-HN=C(OCH3)CH3}2], respectively) and trans- and cis-Z (trans- and cis-[PtCl2(NH3){(Z)-HN=C(OCH3)CH3}], respectively), wi… Show more

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Cited by 51 publications
(45 citation statements)
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“…Previous studies on the determination of the protein binding sites of metal complexes employed the MS identification of peptides cleaved by proteases (e.g. trypsin or Asp-N) [32]. In addition, chemical modifications of specific residues on the protein side chain (e.g.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…Previous studies on the determination of the protein binding sites of metal complexes employed the MS identification of peptides cleaved by proteases (e.g. trypsin or Asp-N) [32]. In addition, chemical modifications of specific residues on the protein side chain (e.g.…”
Section: Resultsmentioning
confidence: 99%
“…The reactivity of several metal anticancer compounds with model proteins such as cytochrome c or ubiquitin has been studied using ESI MS [29][30][31][32]. Combined, these studies show that ESI MS allows rapid and unambiguous identification of the nature of protein-bound metal-containing molecular fragments.…”
Section: Introductionmentioning
confidence: 99%
“…In a recent paper reporting the reactions of four iminoether platinum(II) compounds with horse heart cytochrome c (cyt c), [19] the occurrence of extensive hydrolysis/ amminolysis (the latter fostered by the presence of ammonium carbonate buffer) of the iminoether ligand(s) and formation of the corresponding amides/amidines was noted. The hydrolysis/amminolysis reaction appeared to be fostered by the presence of the protein; therefore, the occurrence of similar reactions in the biological milieu cannot be excluded.…”
Section: Discussionmentioning
confidence: 99%
“…A single methionine appears to be the preferential binding site in the case of cytochrome c (Met 65), which therefore appears to be a quite simple model for this type of investigation [69]. Once more, a striking difference has been observed between cis-Pt and trans-Pt complexes.…”
Section: Other Proteinsmentioning
confidence: 98%