Journal ArticleDOI
Characterisation of cisplatin binding sites in human serum proteins using hyphenated multidimensional liquid chromatography and ESI tandem mass spectrometry.
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TLDR
Cisplatin binding sites in human serum proteins have been characterised by using combined multidimensional liquid chromatography and ESI tandem mass spectrometry (MudPIT).Abstract:
Cisplatin binding sites in human serum proteins have been characterised by using combined multidimensional liquid chromatography and ESI tandem mass spectrometry (MudPIT). Following incubation periods of 3 h for cisplatin-blood serum mixtures and subsequent trypsin digestion, MS-MS spectra were recorded for individual peptides that had been separated by SCX and RP liquid chromatography. Matching of the MS-MS spectra to theoretical sequences that were generated for human proteins in the SWISS-PROT database led to the identification of specific binding sites in human serum albumin (HSA), serotransferrin (Trfe) and other abundant serum proteins (A2mg, A1at, Apoa1, Apoa2). The cisplatin coordination sites in HSA and Trfe were confirmed by independent MudPIT studies on cisplatin reaction mixtures with the individual proteins. A total of five specific binding sites were identified for HSA, including the cysteine residue C34, two methionine sites (M329, M548) and the tyrosine and aspartate O-donor sites Y150 (or Y148) and D375 (or E376). Methionine-256 was established as a cisplatin coordination site for Trfe in addition to the O-donor sites E265, Y314, E385 and T457. Inspection of the protein structures indicates that the preferred residues belong either to peripheral alpha helices or to flexible loops within the protein-binding pockets. O-donor residues dominate as cisplatin binding sites for other abundant serum proteins.read more
Citations
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Thirty Years of the Drug Candidate NAMI‐A and the Myths in the Field of Ruthenium Anticancer Compounds: A Personal Perspective
TL;DR: A personal overview of the ruthenium drug candidate NAMI-A, almost 30 years after its synthesis and the discovery of its unprecedented antimetastatic properties in animal models at nontoxic dosages, is given in this article.
Journal ArticleDOI
Interactions of anticancer Pt compounds with proteins: an overlooked topic in medicinal inorganic chemistry?
TL;DR: A critical discussion about the possible role of Pt-protein interactions in the mechanisms of action of platinum anticancer compounds is presented in this paper, with particular focus on the characterization of the Pt−protein interactions at a molecular level, using different biophysical and analytical methods.
Journal ArticleDOI
Cisplatin binding to proteins: A structural perspective
Luigi Messori,Antonello Merlino +1 more
TL;DR: Analysis of the structural features of cisplatin and its protein derivatives, integrated with selected results arising from the application of other biophysical methods on strictly related systems, allows an overall elucidation of the protein platination process and offers a more comprehensive understanding of the mode of action of cisplant and its parent Pt-based drugs.
Journal ArticleDOI
Transferrin serves as a mediator to deliver organometallic ruthenium(II) anticancer complexes into cells.
TL;DR: HTf can serve as a mediator for the targeting delivery of Ru(arene) anticancer complexes while deactivating cisplatin, and the binding to holo-hTf well preserved the bioavailability of the ruthenium complexes.
Journal ArticleDOI
Cisplatin binding to human serum albumin: a structural study
TL;DR: Structural data unambiguously prove that cisplatin mainly binds to His105 and Met329 side chains; additional binding sites are detected at His288, Met298, and Met548 and at His535, His67 and His247.
References
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A Model for Random Sampling and Estimation of Relative Protein Abundance in Shotgun Proteomics
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An Automated Multidimensional Protein Identification Technology for Shotgun Proteomics
TL;DR: An automated method for shotgun proteomics named MudPIT, which combines multidimensional liquid chromatography with electrospray ionization tandem mass spectrometry, improves the overall analysis of proteomes by identifying proteins of all functional and physical classes.
Journal ArticleDOI
Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation
TL;DR: Using APEX, it is demonstrated that 73% of the variance in yeast protein abundance is explained by mRNA abundance, with the number of proteins per mRNA log-normally distributed about ∼5,600 (∼540 in E. coli) protein molecules/mRNA.
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Interactions of antitumor metallodrugs with serum proteins: advances in characterization using modern analytical methodology.
TL;DR: Platinum coordination compounds have been successfully applied in cancer chemotherapy for more than 25 years since the introduction of the parent compound for this class of antitumor agents, namely, cis-[diamminedichloroplatinum(II)] (1) known as cisplatin 1 (for structural formula, see Figure 1).