Biophysical characterisation of adducts formed between anticancer metallodrugs and selected proteins: New insights from X-ray diffraction and mass spectrometry studies

Casini, Angela; Guerri, Annalisa; Gabbiani, Chiara; Messori, Luigi

doi:10.1016/j.jinorgbio.2007.12.022

Cited by 81 publications

(59 citation statements)

References 69 publications

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“…In addition, metallation of specific amino acid residues, affecting the function of biologically crucial proteins through the formation of strong coordination (covalent) bonds, might play a relevant role in the overall toxicological profile of metalbased drugs [19][20][21]. Indeed, a number of reviews on metallodrug-protein interactions have been published that explore various aspects of their relevance to anticancer activity [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Exploring metallodrug–protein interactions by mass spectrometry: comparisons between platinum coordination complexes and an organometallic ruthenium compound

et al. 2009

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Electrospray ionisation mass spectrometry was used to analyse the reactions of metal compounds with mixtures of selected proteins. Three representative medicinally relevant compounds, cisplatin, transplatin and the organometallic ruthenium compound RAPTA-C, were reacted with a pool of three proteins, ubiquitin, cytochrome c and superoxide dismutase, and the reaction products were analysed using high-resolution mass spectrometry. Highly informative electrospray ionisation mass spectra were acquired following careful optimisation of the experimental conditions. The formation of metal-protein adducts was clearly observed for the three proteins. In addition, valuable information was obtained on the nature of the proteinbound metallofragments, on their distribution among the three different proteins and on the binding kinetics. The platinum compounds were less reactive and considerably less selective in protein binding than RAPTA-C, which showed a high affinity towards ubiquitin and cytochrome c, but not superoxide dismutase. In addition, competition studies between cisplatin and RAPTA-C showed that the two metallodrugs have affinities for the same amino acid residues on protein binding.

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Section: Introductionmentioning

confidence: 99%

Exploring metallodrug–protein interactions by mass spectrometry: comparisons between platinum coordination complexes and an organometallic ruthenium compound

et al. 2009

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“…Therefore, ESI-MS can be used for the molecular characterization of these adducts, as described by Messori and co-workers. 37 Mefenamic acid (M) has a nominal mass of 241.2Da. The ESI(+)-MS spectrum (Figure 1 ).…”

Section: Resultsmentioning

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Soft Ionization of Metallo-Mefenamic Using Electrospray Ionization Mass Spectrometry

Abdelhamid¹,

Wu²

2015

Mass Spectrometry Letters

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Detection of mefenamic acid (M, non-steroidal anti-inflammatory drug, NSAIDs) and its metallodrug was investigated using electrospray ionization mass spectrometry (ESI-MS) and fluorescence spectroscopy. ESI-MS data (500 µL, 1×10-3 M) revealed high detection sensitivity for the drug and metallodrug. ESI-MS spectra revealed peaks at 242, 580, and 777 Da corresponding to [M+H]+, [63Cu(M-H)2(H2O)2+H]+, and [56Fe(M-H)3+H]+, respectively. The metal:mefenamic ratios of ESI-MS spectra are in complete agreement with the fluorescence spectroscopy results (1:2 for Cu(II) and 1:3 for Fe(III)). ESI is a soft ionization technique that can be used on labile metallo-mefenamic acids and is promising for the detection of these species in environmental samples and biological fluids.

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“…[104,110,111] Interestingly, while previous studies using different investigational methods, including MS, showed that cisplatin, transplatin, oxaliplatin and carboplatin possess different stabilities and reactivity with protein/peptides in physiological media, MS revealed that the compounds' behaviour towards Cyt c is quite similar. In most cases, the main adduct detected on the MS spectra corresponds to a 1:1 Pt/protein adduct.…”

Section: Ubiquitin (Ub)mentioning

confidence: 99%

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

Wenzel

Casini

2017

Coordination Chemistry Reviews

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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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Biophysical characterisation of adducts formed between anticancer metallodrugs and selected proteins: New insights from X-ray diffraction and mass spectrometry studies

Cited by 81 publications

References 69 publications

Exploring metallodrug–protein interactions by mass spectrometry: comparisons between platinum coordination complexes and an organometallic ruthenium compound

Exploring metallodrug–protein interactions by mass spectrometry: comparisons between platinum coordination complexes and an organometallic ruthenium compound

Soft Ionization of Metallo-Mefenamic Using Electrospray Ionization Mass Spectrometry

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

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