A case of extensive protein platination: the reaction of lysozyme with a Pt(<scp>ii</scp>)–terpyridine complex

Ferraro, Giarita; Marzo, Tiziano; Infrasca, Teresa; Cilibrizzi, Agostino; Vilar, Ramón; Messori, Luigi; Merlino, Antonello

doi:10.1039/c8dt01254g

Cited by 24 publications

(23 citation statements)

References 32 publications

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“…These findings could indicate that at least an undefined amount of compound 1 could be degraded during the encapsulation process. This would not be surprising, since the metal complex is not stable at the high alkaline pH used for the encapsulation and degradation of compound 1 upon interaction with proteins has been already observed [23]. Thus, it is likely that compound 1 and/or compound 1 fragments react with hsAFt during the encapsulation process.…”

Section: Discussionmentioning

confidence: 94%

Preparation, structure, Cytotoxicity and Mechanism of Action of ferritin-Pt(II) Terpyridine Compound Nanocomposites

Ferraro

Pica

Petruk

et al. 2018

Nanomedicine (Lond.)

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Aim: A Pt(II)-terpyridine compound, bearing two piperidine substituents at positions 2 and 2' of the terpyridine ligand (1), is highly cytotoxic and shows a mechanism of action distinct from cisplatin. 1 has been incorporated within the ferritin nanocage (AFt). Materials & methods: Spectroscopic and crystallographic data of the Pt(II)-AFt nanocomposite have been collected and in vitro anticancer activity has been explored using cancer cells. Results: Pt(II)-containing fragments bind His49, His114 and His132. Pt(II)-AFt nanocomposite is less cytotoxic than 1, but it is more toxic than cisplatin at high concentrations. The Pt(II)-AFt nanocomposite triggers necrosis in cancer cells, as free 1 does. Conclusions: Pt(II)-AFt nanocomposites are promising vehicles to deliver Pt-based drugs to cancer cells.

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Section: Discussionmentioning

confidence: 94%

Preparation, structure, Cytotoxicity and Mechanism of Action of ferritin-Pt(II) Terpyridine Compound Nanocomposites

Ferraro

Pica

Petruk

et al. 2018

Nanomedicine (Lond.)

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“…However, these metal compounds can also interact with proteins and peptides. Crystallographic studies have provided detailed information about the structure of the adducts formed in the reaction of proteins with cisplatin [ 2 , 3 , 4 , 5 ], trans -Pt complexes [ 6 ], cis -Pt(NH 3 ) 2 I 2 [ 7 ], carboplatin [ 2 , 3 , 4 , 8 , 9 ], oxaliplatin [ 10 ] and other Pt(II) complexes, like those bearing O , S -bidentate [ 11 , 12 ] or terpyridine ligands [ 13 ]. The ligands coordinated to Pt(II) determine the reactivity of these complexes with proteins and the binding sites.…”

Section: Introductionmentioning

confidence: 99%

“…The ligands coordinated to Pt(II) determine the reactivity of these complexes with proteins and the binding sites. For example, in the interaction with the model protein hen egg white lysozyme (HEWL), cisplatin [ 3 , 13 , 14 ], carboplatin, trans -Pt derivatives [ 8 , 13 ] and cis -Pt(NH 3 ) 2 I 2 [ 8 , 15 ] bind His15, oxaliplatin binds Asp119 [ 16 , 17 ], whereas a Pt(II) terpyridine compound binds the side chains of Lys1, Glu7, His15, Arg14 and His15, Lys13, Lys96, Lys97 and Asn93 [ 13 ]. These bioinorganic complexes were also investigated in their kinetic and thermodynamic features [ 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Platinum(II) O,S Complexes Inhibit the Aggregation of Amyloid Model Systems

Florio

Malfitano

Somma

et al. 2019

IJMS

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Platinum(II) complexes with different cinnamic acid derivatives as ligands were investigated for their ability to inhibit the aggregation process of amyloid systems derived from Aβ, Yeast Prion Protein Sup35p and the C-terminal domain of nucleophosmin 1. Thioflavin T binding assays and circular dichroism data indicate that these compounds strongly inhibit the aggregation of investigated peptides exhibiting IC50 values in the micromolar range. MS analysis confirms the formation of adducts between peptides and Pt(II) complexes that are also able to reduce amyloid cytotoxicity in human SH-SY5Y neuroblastoma cells. Overall data suggests that bidentate ligands based on β-hydroxy dithiocinnamic esters can be used to develop platinum or platinoid compounds with anti-amyloid aggregation properties.

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“…Hen white egg lysozyme (HEWL) has been extensively employed in the MetMed lab in Florence [ 13 , 14 ] for the preliminary interaction studies via ESI MS of metallodrug–protein interactions as it is a small protein with a great ionizability in the ESI source, giving rise to well resolved ESI MS spectra. In addition, HEWL is well prone to crystallization allowing the obtainment of independent crystallographic data on the same systems.…”

Section: Resultsmentioning

confidence: 99%

Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands

Sacco

Tarchi

Ferraro

et al. 2021

IJMS

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Three novel platinum(II) complexes bearing N-heterocyclic ligands, i.e., Pt2c, Pt-IV and Pt-VIII, were previously prepared and characterized. They manifested promising in vitro anticancer properties associated with non-conventional modes of action. To gain further mechanistic insight, we have explored here the reactions of these Pt compounds with a few model proteins, i.e., hen egg white lysozyme (HEWL), bovine pancreatic ribonuclease (RNase A), horse heart cytochrome c (Cyt-c) and human serum albumin (HSA), primarily through ESI MS analysis. Characteristic and variegate patterns of reactivity were highlighted in the various cases that appear to depend both on the nature of the Pt complex and of the interacting protein. The protein-bound Pt fragments were identified. In the case of the complex Pt2c, the adducts formed upon reaction with HEWL and RNase A were further characterized by solving the respective crystal structures: this allowed us to determine the exact location of the various Pt binding sites. The implications of the obtained results are discussed in relation to the possible mechanisms of action of these innovative anticancer Pt complexes.

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A case of extensive protein platination: the reaction of lysozyme with a Pt(ii)–terpyridine complex

Abstract: The interaction between a Pt(ii)–terpyridine cytotoxic compound and the model protein lysozyme has been investigated by X-ray crystallography and electrospray mass spectrometry under different experimental conditions. The compound shows a high reactivity with the model protein.

Cited by 24 publications

References 32 publications

Preparation, structure, Cytotoxicity and Mechanism of Action of ferritin-Pt(II) Terpyridine Compound Nanocomposites

Preparation, structure, Cytotoxicity and Mechanism of Action of ferritin-Pt(II) Terpyridine Compound Nanocomposites

Platinum(II) O,S Complexes Inhibit the Aggregation of Amyloid Model Systems

Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands

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