In this work, we have analysed the binding of the Pt(II) complexes ([PtCl(4′-phenyl-2,2′:6′,2″-terpyridine)](CF3SO3) (1), [PtI(4′-phenyl-2,2′:6′,2″-terpyridine)](CF3SO3) (2) and [PtCl(1,3-di(2-pyridyl)benzene) (3)] 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 3 for the proteins is low. On the other hand, 1 and 2 strongly bind them, but with major binding mode differences when switching from HEWL to RNase A. Both 1 and 2 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 2, in agreement with iodine lability higher than chlorine.
Thermodynamic Evaluation of the Interactions between Anticancer Pt(II) Complexes and Model Proteins
Pelosi, ChiaraPrimo
;Biver, Tarita;Pratesi, Alessandro;Duce, Celia;Gabbiani, Chiara
Penultimo
;Tiné, Maria Rosaria
Ultimo
2021-01-01
Abstract
In this work, we have analysed the binding of the Pt(II) complexes ([PtCl(4′-phenyl-2,2′:6′,2″-terpyridine)](CF3SO3) (1), [PtI(4′-phenyl-2,2′:6′,2″-terpyridine)](CF3SO3) (2) and [PtCl(1,3-di(2-pyridyl)benzene) (3)] 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 3 for the proteins is low. On the other hand, 1 and 2 strongly bind them, but with major binding mode differences when switching from HEWL to RNase A. Both 1 and 2 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 2, in agreement with iodine lability higher than chlorine.File | Dimensione | Formato | |
---|---|---|---|
Manuscript file_pre print.docx
accesso aperto
Tipologia:
Documento in Pre-print
Licenza:
Tutti i diritti riservati (All rights reserved)
Dimensione
2.18 MB
Formato
Microsoft Word XML
|
2.18 MB | Microsoft Word XML | Visualizza/Apri |
2021_molecules-26-02376-v2.pdf
accesso aperto
Tipologia:
Versione finale editoriale
Licenza:
Creative commons
Dimensione
2.08 MB
Formato
Adobe PDF
|
2.08 MB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.