Thermodynamic Evaluation of the Interactions between Anticancer Pt(II) Complexes and Model Proteins

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.

Anticancer Diiron Vinyliminium Complexes: A Structure–Activity Relationship Study

“…During the past years, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) has emerged as a valuable and powerful tool to study the formation of adducts derived from the interaction of metallodrugs with biomolecules [ 76 , 77 , 78 ]. Moreover, this technique allows the identification of the precise nature of the fragments attached to protein side chains and, thus, to infer some relevant mechanistic information [ 79 , 80 , 81 ].…”

Reactions of proteins with a few organopalladium compounds of medicinal interest

“…The selected Pd compounds were initially challenged against the small proteins RNase A and Hen Egg White Lysozyme that are often used for this kind of investigations and the respective ESI MS spectra were recorded. 8…”

Squaraine Dyes as Fluorescent Turn‐on Probes for Mucins: A Step Toward Selectivity†

“…4a-c). Moreover, the presence of a well-defined isosbestic point at 680 nm and a second nonperfect point at ~595 nm suggests multiple cooperative equilibria, thus more than one type of binding (33,34). In addition, to clarify whether S6 can induce a modification of the secondary structure of PGM, circular dichroism (CD) has been investigated.…”