title: Protein Metalation by Anticancer Metallodrugs: A Joint ESI MS and XRD Investigative Strategy.
abstract: Interactions of metal-based drugs with proteins and consequent adduct formation (the so-called "protein metalation" process) play a key role in the mode of action of several anticancer agents and in determining their toxicological profile. Through a novel investigative strategy grounded on the combined use of electrospray ionization mass spectrometry (ESI MS) and biological macromolecule X-ray crystallography we show that it is possible to clarify in depth the metalation process of small model proteins; a number of instructive examples are provided. Recently, this kind of investigative approach has been extended to bigger proteins such as human serum albumin and horse spleen ferritin, with rather encouraging results. Overall, by application of this strategy, metalation of proteins caused by anticancer metallodrugs can be disclosed in the molecular detail.
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126, Napoli, Italy) and CNR Institute of Biostructure and Bioimages, Via Mezzocannone 16, 80100, Napoli (Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Merlino
authors.affiliation: Department of Chemistry and Industrial Chemistry, University of Pisa, via Moruzzi, 13, 56124, Pisa, Italy.|Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto fiorentino (FI), Italy.
authors.forename: Tiziano
authors.identifier: http://orcid.org/0000-0002-2567-3637
authors.initials: T
authors.lastname: Marzo
authors.affiliation: Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto fiorentino (FI), Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D002945:Cisplatin / Q000737:chemistry; D018360:Crystallography, X-Ray; D005293:Ferritins / Q000737:chemistry*; D006736:Horses; D006801:Humans; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; D012709:Serum Albumin; D005293:Ferritins; D002945:Cisplatin
keywords: X-ray crystallography; anticancer compounds; mass spectrometry; metallodrugs; protein metalation