Thermodynamic Evaluation of the Interactions between Anticancer Pt(II) Complexes and Model Proteins
In this work, we have analysed the binding of the Pt(II) complexes ([PtCl(4′-phenyl-2,2′:6′,2″-terpyridine)](CF<sub>3</sub>SO<sub>3</sub>) (<b>1</b>), [PtI(4′-phenyl-2,2′:6′,2″-terpyridine)](CF<sub>3</sub>SO<sub>3</sub>) (<b>2</b&g...
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MDPI AG
2021-04-01
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| Online Access: | https://www.mdpi.com/1420-3049/26/8/2376 |
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| author | Chiara Pelosi Francesca Saitta Caterina Zerino Giovanni Canil Tarita Biver Alessandro Pratesi Celia Duce Dimitrios Fessas Chiara Gabbiani Maria Rosaria Tiné |
| author_facet | Chiara Pelosi Francesca Saitta Caterina Zerino Giovanni Canil Tarita Biver Alessandro Pratesi Celia Duce Dimitrios Fessas Chiara Gabbiani Maria Rosaria Tiné |
| author_sort | Chiara Pelosi |
| collection | DOAJ |
| description | In this work, we have analysed the binding of the Pt(II) complexes ([PtCl(4′-phenyl-2,2′:6′,2″-terpyridine)](CF<sub>3</sub>SO<sub>3</sub>) (<b>1</b>), [PtI(4′-phenyl-2,2′:6′,2″-terpyridine)](CF<sub>3</sub>SO<sub>3</sub>) (<b>2</b>) and [PtCl(1,3-di(2-pyridyl)benzene) (<b>3</b>)] with selected model proteins (hen egg-white lysozyme, HEWL, and ribonuclease A, RNase A). Platinum coordination compounds are intensively studied to develop improved anticancer agents. In this regard, a critical issue is the possible role of Pt-protein interactions in their mechanisms of action. Multiple techniques such as differential scanning calorimetry (DSC), electrospray ionization mass spectrometry (ESI-MS) and UV-Vis absorbance titrations were used to enlighten the details of the binding to the different biosubstrates. On the one hand, it may be concluded that the affinity of <b>3</b> for the proteins is low. On the other hand, <b>1</b> and <b>2</b> strongly bind them, but with major binding mode differences when switching from HEWL to RNase A. Both <b>1</b> and <b>2</b> bind to HEWL with a non-specific (DSC) and non-covalent (ESI-MS) binding mode, dominated by a 1:1 binding stoichiometry (UV-Vis). ESI-MS data indicate a protein-driven chloride loss that does not convert into a covalent bond, likely due to the unfavourable complexes’ geometries and steric hindrance. This result, together with the significant changes of the absorbance profiles of the complex upon interaction, suggest an electrostatic binding mode supported by some stacking interaction of the aromatic ligand. Very differently, in the case of RNase A, slow formation of covalent adducts occurs (DSC, ESI-MS). The reactivity is higher for the iodo-compound <b>2</b>, in agreement with iodine lability higher than chlorine. |
| first_indexed | 2024-03-10T12:11:06Z |
| format | Article |
| id | doaj.art-fac4e7de88694d1798a2b5c3796a68c5 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T12:11:06Z |
| publishDate | 2021-04-01 |
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| series | Molecules |
| spelling | doaj.art-fac4e7de88694d1798a2b5c3796a68c52023-11-21T16:13:18ZengMDPI AGMolecules1420-30492021-04-01268237610.3390/molecules26082376Thermodynamic Evaluation of the Interactions between Anticancer Pt(II) Complexes and Model ProteinsChiara Pelosi0Francesca Saitta1Caterina Zerino2Giovanni Canil3Tarita Biver4Alessandro Pratesi5Celia Duce6Dimitrios Fessas7Chiara Gabbiani8Maria Rosaria Tiné9Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, ItalyDipartimento di Scienze per gli Alimenti, la Nutrizione e l’Ambiente, DeFENS, Università degli Studi di Milano, Via Celoria 2, 20133 Milano, ItalyDepartment of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, ItalyDepartment of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, ItalyDepartment of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, ItalyDepartment of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, ItalyDepartment of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, ItalyDipartimento di Scienze per gli Alimenti, la Nutrizione e l’Ambiente, DeFENS, Università degli Studi di Milano, Via Celoria 2, 20133 Milano, ItalyDepartment of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, ItalyDepartment of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, ItalyIn this work, we have analysed the binding of the Pt(II) complexes ([PtCl(4′-phenyl-2,2′:6′,2″-terpyridine)](CF<sub>3</sub>SO<sub>3</sub>) (<b>1</b>), [PtI(4′-phenyl-2,2′:6′,2″-terpyridine)](CF<sub>3</sub>SO<sub>3</sub>) (<b>2</b>) and [PtCl(1,3-di(2-pyridyl)benzene) (<b>3</b>)] with selected model proteins (hen egg-white lysozyme, HEWL, and ribonuclease A, RNase A). Platinum coordination compounds are intensively studied to develop improved anticancer agents. In this regard, a critical issue is the possible role of Pt-protein interactions in their mechanisms of action. Multiple techniques such as differential scanning calorimetry (DSC), electrospray ionization mass spectrometry (ESI-MS) and UV-Vis absorbance titrations were used to enlighten the details of the binding to the different biosubstrates. On the one hand, it may be concluded that the affinity of <b>3</b> for the proteins is low. On the other hand, <b>1</b> and <b>2</b> strongly bind them, but with major binding mode differences when switching from HEWL to RNase A. Both <b>1</b> and <b>2</b> bind to HEWL with a non-specific (DSC) and non-covalent (ESI-MS) binding mode, dominated by a 1:1 binding stoichiometry (UV-Vis). ESI-MS data indicate a protein-driven chloride loss that does not convert into a covalent bond, likely due to the unfavourable complexes’ geometries and steric hindrance. This result, together with the significant changes of the absorbance profiles of the complex upon interaction, suggest an electrostatic binding mode supported by some stacking interaction of the aromatic ligand. Very differently, in the case of RNase A, slow formation of covalent adducts occurs (DSC, ESI-MS). The reactivity is higher for the iodo-compound <b>2</b>, in agreement with iodine lability higher than chlorine.https://www.mdpi.com/1420-3049/26/8/2376antitumoral complexPt(II) coordinationcalorimetrybinding mechanisminteraction complex-protein |
| spellingShingle | Chiara Pelosi Francesca Saitta Caterina Zerino Giovanni Canil Tarita Biver Alessandro Pratesi Celia Duce Dimitrios Fessas Chiara Gabbiani Maria Rosaria Tiné Thermodynamic Evaluation of the Interactions between Anticancer Pt(II) Complexes and Model Proteins Molecules antitumoral complex Pt(II) coordination calorimetry binding mechanism interaction complex-protein |
| title | Thermodynamic Evaluation of the Interactions between Anticancer Pt(II) Complexes and Model Proteins |
| title_full | Thermodynamic Evaluation of the Interactions between Anticancer Pt(II) Complexes and Model Proteins |
| title_fullStr | Thermodynamic Evaluation of the Interactions between Anticancer Pt(II) Complexes and Model Proteins |
| title_full_unstemmed | Thermodynamic Evaluation of the Interactions between Anticancer Pt(II) Complexes and Model Proteins |
| title_short | Thermodynamic Evaluation of the Interactions between Anticancer Pt(II) Complexes and Model Proteins |
| title_sort | thermodynamic evaluation of the interactions between anticancer pt ii complexes and model proteins |
| topic | antitumoral complex Pt(II) coordination calorimetry binding mechanism interaction complex-protein |
| url | https://www.mdpi.com/1420-3049/26/8/2376 |
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