title: Elucidating the reactivity of Pt(II) complexes with (O,S) bidentate ligands towards DNA model systems.
abstract: In the search for novel platinum-based anticancer therapeutic agents, we have recently established a structural motif of (O,S) bidentate ligands bound to a Pt(II) metal center which is effective against various cancer cell lines. Aiming at further enhancing the cytotoxicity of metal-based drugs, the identification of potential biological targets and elucidation of the mode of action of selected lead compounds is of utmost importance. Here we report our studies on the DNA interaction of three representative Pt(II) complexes of the investigated series, using various model systems and analytical techniques. In detail, CD spectroscopy as well as ESI-MS and MS(2) techniques were applied to gain an overall picture of the binding properties of this class of (O,S) bidentate Pt(II) compounds with defined oligonucleotide sequences in single strand, duplex or G-quadruplex form, as well as with the nucleobase 9-methylguanine. On the whole, it was demonstrated that the tested compounds interact with DNA and produce conformational changes of different extents depending on the sequence and structure of the examined oligonucleotide. Guanine was established as the preferential target within the DNA sequence, but in the absence or unavailability of guanines, alternative binding sites can be addressed. The implications of these results are thoroughly discussed.
authors.affiliation: Institute of Inorganic and Analytical Chemistry, Friedrich-Schiller-University Jena, Humboldtstraße 8, 07743 Jena, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Mügge
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 21, 80126 Napoli, Italy; Institute of Biostructures and Bioimages, Via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Musumeci
authors.affiliation: CISM, Mass Spectrometry Center, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, (FI), Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Michelucci
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 21, 80126 Napoli, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Porru
authors.affiliation: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, (FI), Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Marzo
authors.affiliation: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, (FI), Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Massai
authors.affiliation: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, (FI), Italy. Electronic address: luigi.messori@unifi.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
authors.affiliation: Institute of Inorganic and Analytical Chemistry, Friedrich-Schiller-University Jena, Humboldtstraße 8, 07743 Jena, Germany; Jena Center for Soft Matter (JCSM), Philosophenweg 7, 07743 Jena, Germany. Electronic address: wolfgang.weigand@uni-jena.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weigand
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 21, 80126 Napoli, Italy. Electronic address: daniela.montesarchio@unina.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Montesarchio
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis; D001665:Binding Sites; D056831:Coordination Complexes / Q000138:chemical synthesis*; D054856:G-Quadruplexes; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D008024:Ligands; D008956:Models, Chemical; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D009944:Organoplatinum Compounds; C116701:9-methylguanine; D010984:Platinum; D006147:Guanine
keywords: CD spectroscopy; DNA interaction; ESI-MS spectrometry; Guanine binding; Pt(II)-based anticancer agents