Interactions of Antitumor Metallodrugs with Serum Proteins:  Advances in Characterization Using Modern Analytical Methodology

Timerbaev, Andrei R.; Hartinger, Christian G.; Aleksenko, Svetlana S.; Keppler, Bernhard K.

doi:10.1021/cr040704h

Cited by 586 publications

(423 citation statements)

References 158 publications

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“…Both these aqua species and the parent drug are responsible for the reaction and binding properties of cisplatin. This agrees with previous observations achieved by other methods [20,30].…”

Section: Cisplatin-hb Interactionsupporting

confidence: 94%

“…This led in particular to a growing number of metallodrug-protein investigations performed using valuable techniques superior to contemporary methods in the field. A recent review summarizes the progress made in the applications of modern analytical methodologies for antitumor metallodrug-protein studies [20]. ESI-MS was recently shown as an extremely useful tool for studying the cisplatin-protein interactions [19,[21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

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Investigation of interaction between human hemoglobin A₀ and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection

Lemma

Mandal

et al. 2008

J of Separation Science

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Original PaperInvestigation of interaction between human hemoglobin A 0 and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection CIEF with whole column imaging detection (WCID) was used to investigate the interaction of platinum-based anticancer drugs, cis-platinum(II) diamine dichloride (cisplatin) and [SP-4-2-{1R-trans)]-(1,2-cyclohexanediamine-N,N9)[ethanedioata(2 -)-O,O9]platinum (oxaliplatin), with human hemoglobin A 0 (Hb). This technique facilitates the investigation and characterization of the formation of adducts between drugs and proteins. Cisplatin and oxaliplatin were mixed with the target protein at different concentrations (0:1, 1:1, 1:10, 1:50, and 1:100), and the reaction mixtures were incubated for 0, 0.5, 1, 12, 24, 48, and 72 h at 378C in a water-bath. The focused Hb -drug adduct profiles were imaged by WCID. At higher drug to protein molar ratios (for both oxaliplatin and cisplatin), the results exhibit significant changes in the peak shapes and heights, which may indicate the destabilization of the protein. However, the conformational change was less evident at lower molar ratios. In addition, a major pI shift was observed for the oxaliplatin reaction mixtures (for 1:10, 1:50, and 1:100 ratios). In comparison with previously reported findings obtained by other analytical methods, conclusions were drawn about the validity of CIEF as a simple and convenient method for the investigation of protein -drug interactions. These results may provide useful information for further understanding the activity and toxicity of these chemotherapeutic drugs and improving their clinical performance.

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“…Both these aqua species and the parent drug are responsible for the reaction and binding properties of cisplatin. This agrees with previous observations achieved by other methods [20,30].…”

Section: Cisplatin-hb Interactionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Investigation of interaction between human hemoglobin A₀ and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection

Lemma

Mandal

et al. 2008

J of Separation Science

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“…The metal ion in the RhCp* -HSA system can be also bound by other solvent-exposed residues considering the high number of binding sites. Coordination preferences for His, Met and Cys residues are suggested for Ru(II/III) complexes [64,65]. Tyr residue of peptides has been recently shown to coordinate to RhCp* via η 6 bonding mode [66].…”

Section: Figmentioning

confidence: 99%

Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2ʹ-bipyridine and ethylenediamine and their interaction with human serum albumin

Enyedy

Mészáros

Dömötör

et al. 2015

Journal of Inorganic Biochemistry

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Complex formation equilibrium processes of the (N,N) donor containing 2,2'-bipyridine (bpy) and ethylenediamine (en) with (η 5 -pentamethylcyclopentadienyl)rhodium(III) were investigated in aqueous solution via pH-potentiometry, 1 H NMR spectroscopy, and UV-Vis spectrophotometry in the absence and presence of chloride ions. 2+ , and formation of ternary HSA-RhCp*-ligand adducts was proved. In the case of the deferiprone complex, the RhCp* fragment is cleaved off when HSA is loaded with low equivalents of the compound.

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“…At physiological pH, the protein exhibits a helical conformation, with 17 disulfide bonds and 2 residues in hydrophobic cavities accessible for potential metal binding/interaction (Cys-34 and Trp-214). [151] Human serum transferrin (hTf) is found in blood at a concentration of around 35 M, and is composed by 679 amino acids; its main role is to transport Fe(III) ions (up to two Fe(III) bound per mole). Each iron binding site in hTf exhibits a distorted octahedral geometry between two tyrosines, one histidine and one asparagine, with a bidentate carbonate ion acting as a synergistic anion in the process of Fe(III) binding.…”

Section: Interactions Of Metallodrugs With Serum and Serum Proteinsmentioning

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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Interactions of Antitumor Metallodrugs with Serum Proteins: Advances in Characterization Using Modern Analytical Methodology

Cited by 586 publications

References 158 publications

Investigation of interaction between human hemoglobin A₀ and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection

Investigation of interaction between human hemoglobin A₀ and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection

Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2ʹ-bipyridine and ethylenediamine and their interaction with human serum albumin

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

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Interactions of Antitumor Metallodrugs with Serum Proteins: Advances in Characterization Using Modern Analytical Methodology

Cited by 586 publications

References 158 publications

Investigation of interaction between human hemoglobin A0 and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection

Investigation of interaction between human hemoglobin A0 and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection

Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2ʹ-bipyridine and ethylenediamine and their interaction with human serum albumin

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

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Investigation of interaction between human hemoglobin A₀ and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection

Investigation of interaction between human hemoglobin A₀ and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection