Cisplatin−Protein Adducts Are Efficiently Removed by Glutathione but Not by 5‘-Guanosine Monophosphate

Peleg-Shulman, Tal; Gibson, Dan

doi:10.1021/ja005854y

Cited by 74 publications

(71 citation statements)

References 16 publications

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“…Effects of replacing the ammine ligands of cis-[Pt(NH 3 ) 2 Cl 2 ] on the binding kinetics The reaction of 1 Eq cisplatin with Ub yields four adducts that can be distinguished by mass spectrometry [13,14,15]. These adducts correspond to two monofunctional adducts, trifunctional adduct cis-[Pt(NH 3 )(Ub)] (M r =8,775).…”

Section: Synthesis and Characterization Of The Complexesmentioning

confidence: 99%

Ligand effects on the binding of cis- and trans-[PtCl2Am1Am2] to proteins

Najajreh

Peleg-Shulman

Moshel³

et al. 2003

J Biol Inorg Chem

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As part of a systematic study of the basic principles that govern the formation and reactivity of Pt-protein adducts, we report the effect of substituting the amine ligand of cis- and trans-[PtCl(2)(NH(3))(2)] complexes with bulkier planar aromatic or nonplanar cyclic amine ligands on the binding properties of the complexes to ubiquitin and to horse heart myoglobin. The ligand replacement had a different effect on the cis or trans isomers investigated. In the cis-Pt complexes, replacing one or both amine ligands by piperidine or 4-picoline dramatically decreased the binding of the complexes to the proteins studied, whereas in the substituted trans-Pt complexes replacement of the amine by a piperidine or 4-picoline increased the binding rate. This behavior may have to do with the different preferred binding sites of the cis- and trans-Pt complexes. The bulkier cis- or trans-Pt complexes investigated also did not display a preference for Met1 of ubiquitin, possibly owing to steric constraints imposed by the substituted ligands. The introduction of a charged piperazine ligand significantly decreased the rate of binding to the protein, possibly owing to electrostatic interactions or hydrogen-bond formations with the surface of the protein. The binding of the complexes to ubiquitin and myoglobin does not disrupt the folding of the proteins as judged by electrospray ionization mass spectrometry.

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Section: Synthesis and Characterization Of The Complexesmentioning

confidence: 99%

Ligand effects on the binding of cis- and trans-[PtCl2Am1Am2] to proteins

Najajreh

Peleg-Shulman

Moshel³

et al. 2003

J Biol Inorg Chem

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“…In fact, GSH is present in cells at various concentrations (0.5-10 mM) [74] and is believed to induce detoxification of platinum and ruthenium-based metallodrugs. [75] It has therefore been widely used in competitive MS experiments with metallodrug-biomolecule adducts. A few examples of such competition studies will be reported later in this chapter.…”

Section: Platinum Complexesmentioning

confidence: 99%

“…[75] Peaks in the mass spectra were attributed to Pt(NH 3 )(Ub)(GSH) adducts, where GSH is most likely bound to Pt(II) in a monodentate fashion. Similarly, the stability of the adducts formed between oxaliplatin and 5'-GMP in presence of GSH has been evaluated using HPLC coupled to ESI-ToF-MS. [85] The ruthenium complex was characterised as forming very stable adducts with the single stranded oligonucleotides.…”

Section: Competition Experiments With Gshmentioning

confidence: 99%

Mass spectrometry as a powerful tool to study therapeutic metallodrugs speciation mechanisms: Current frontiers and perspectives

Wenzel

Casini

2017

Coordination Chemistry Reviews

108

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Metal-based compounds form a promising class of therapeutic agents, whose mechanisms of action still need to be elucidated, and that are in general prone to undergo extensive speciation in physiological environment. Thus, determination of the fate of the metal compounds in complex biological systems, contributing to their overall pharmacological and toxicological profiles, is important to develop more rationalised and targeted metal-based drugs. To these aims, a number of spectroscopic and biophysical methods, as well as analytical techniques, are nowadays extensively applied to study the reactivity of metal complexes with different biomolecules (e.g. nucleic acids, proteins, buffer components). Among the various techniques, molecular mass spectrometry (MS) has emerged in the last decade as a major tool to characterise the interactions of metallodrugs at a molecular level. In this review, we present an overview of the information available on the reactivity of various families of therapeutic metallodrugs (mainly anticancer compounds based on Pt, Ru, Au and As) with biomolecules studied by different MS techniques, including high-resolution ESI-, MALDI-and ion mobility-MS among others. Representative examples on the potential of the MS approach to study non-covalent interactions are also discussed. The review is organized to present results obtained on samples with different degrees of complexity, from the interactions of metal compounds with small model nucleophiles (amino acids and nucleobases), model peptides/oligonucleotides, target proteins/nucleic acids, to the analysis of serum, cell extracts and tissue samples. The latter requiring combination of proteomic methods with advanced MS techniques. Correlations between molecular reactivity of metallodrugs and biological activity are hard to establish, but differences in the reactivity of metallodrugs to biomolecules and their different adducts, as revealed by MS methods, may indicate differences in their modes of action. Overall, the knowledge offered by MS methods on metallodrugs speciation is invaluable to establish new rules and define new trends in the periodic table aimed at rationalizing the behavior of metal compounds in complex living systems. Keywordsmetal-based drugs; proteins; nucleic acids; mass spectrometry; metallomics. Corresponding Author Angela Casini Corresponding Author's InstitutionCardiff University To view all the submission files, including those not included in the PDF, click on the manuscript title on your EVISE Homepage, then click 'Download zip file'. Order of Authors 1 Answers to Reviewers Reviewer 1 The authors have made some effort to answer suggestions and the manuscript is improved. Since it is a review, there is, strictly, no new information but nevertheless the compilation of data and references could be useful.Answer: no further comments. Liu et al." in place of "Lu et al." iv) Some symbols in the PDF file are not correctly displayed. Reviewer Answer:We have inserted all the minor modifications requested by this rev...

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“…Several other proteins like serum albumin [57][58][59], ubiquitin [60][61][62], myoglobin [61,62], transferrin [63,64], superoxide dismutase [65,66], lysozyme [67], and cytochrome c [68] have been shown to coordinate cisplatin and transplatin mainly through methionine, cysteine, or histidine, and in some instances also through a threonine residue. 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].…”

Section: Other Proteinsmentioning

confidence: 99%

"Platinum on the road": Interactions of antitumoral cisplatin with proteins

Arnesano

Natile

2008

Pure and Applied Chemistry

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When the antitumor activity of cisplatin was discovered, no one would have thought of the existence of specific proteins able to transport Pt across the cell membrane or to specifically recognize DNA modified by this drug. However, such proteins do exist and, furthermore, are specific for the Pt substrate considered. It follows that proteins are deeply involved in managing the biological activity of cisplatin. It is expected that, after the first 20 years in which most of the efforts were devoted to understanding its mode of interaction with DNA and consequent structural and functional alterations, the role of proteins will be more deeply scavenged. How cisplatin can survive the attack of the many platinophiles present in the extracellular and intracellular media is the issue addressed in this article. Significantly, differences are observed between cisplatin, carboplatin, and oxaliplatin.

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Cisplatin−Protein Adducts Are Efficiently Removed by Glutathione but Not by 5‘-Guanosine Monophosphate

Cited by 74 publications

References 16 publications

Ligand effects on the binding of cis- and trans-[PtCl2Am1Am2] to proteins

Ligand effects on the binding of cis- and trans-[PtCl2Am1Am2] to proteins

Mass spectrometry as a powerful tool to study therapeutic metallodrugs speciation mechanisms: Current frontiers and perspectives

"Platinum on the road": Interactions of antitumoral cisplatin with proteins

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