English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/53295
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

Solution behaviour and biomolecular interactions of two cytotoxic trans-platinum(II) complexes bearing aliphatic amine ligands

AuthorsCubo, Leticia; Casini, Angela; Gabbiani, Chiara; Mastrobuoni, Guido; Messori, Luigi; Jiménez-Barbero, Jesús ; Navarro-Ranninger, Carmen; Quiroga, Adoración G.
Keywordscytochromes
cytotoxicity
hydrolysis
platinum
proteins
Issue Date14-Sep-2009
PublisherWiley-VCH
CitationChemistry - A European Journal 15(36):9139-9146(2009)
AbstractA novel trans-platinum(II) complex bearing one dimethylamine (dma) and one methylamine (ma) ligand, namely trans-[PtCl(2)(dma)(ma)], recently synthesised and characterised in our laboratory, displayed relevant antiproliferative properties in vitro, being more active than the parent complex, trans-[PtCl(2)(dma)(ipa)], which has isopropylamine (ipa) in place of methylamine. We have analysed comparatively the solution behaviour of these two complexes under various experimental conditions, and investigated their reactivity with horse heart cytochrome c by mass spectrometry, inductively coupled plasma-optical emission spectroscopy (ICP-OES), 2D [(1)H,(15)N],[(1)H,(13)C] HSQC and [(1)H,(1)H] NOESY NMR. Some important changes that occurred in the [(1)H,(13)C] HSQC NMR spectrum of cytochrome c treated with trans-[PtCl(2)(dma)(ma)] in water, after two days' incubation, most probably arose from direct platinum coordination to the protein side chain; this was proved conclusively by [(1)H,(1)H] NOESY NMR and [(1)H,(15)N] HSQC NMR measurements. Met65 was identified as the primary Pt binding site on cytochrome c. Electrospray mass spectrometry (ESIMS) results provided evidence for extensive platinum-protein adduct formation. A fragment of the [Pt(amine)(amine')] type was established to be primarily responsible for protein metalation. ICP-OES analysis revealed that these trans-platinum(II) complexes bind preferentially to the serum proteins albumin and transferrin rather than to calf thymus DNA. Pt binding to DNA was found to be far lower than in the case of cisplatin. The implications of the results for the mechanism of action of novel cytotoxic trans-platinum complexes are discussed
Description8 páginas, 6 figuras, 2 tablas -- PAGS nros. 9139-9146
Publisher version (URL)http://dx.doi.org/10.1002/chem.200901090
URIhttp://hdl.handle.net/10261/53295
DOI10.1002/chem.200901090
ISSN0947-6539
E-ISSN1521-3765
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
restringido.pdf21,67 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.