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

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 explor...

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Autores principales: Sacco, Francesca, Tarchi, Matteo, Ferraro, Giarita, Merlino, Antonello, Facchetti, Giorgio, Rimoldi, Isabella, Messori, Luigi, Massai, Lara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508948/
https://www.ncbi.nlm.nih.gov/pubmed/34638887
http://dx.doi.org/10.3390/ijms221910551
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author Sacco, Francesca
Tarchi, Matteo
Ferraro, Giarita
Merlino, Antonello
Facchetti, Giorgio
Rimoldi, Isabella
Messori, Luigi
Massai, Lara
author_facet Sacco, Francesca
Tarchi, Matteo
Ferraro, Giarita
Merlino, Antonello
Facchetti, Giorgio
Rimoldi, Isabella
Messori, Luigi
Massai, Lara
author_sort Sacco, Francesca
collection PubMed
description 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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spelling pubmed-85089482021-10-13 Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands Sacco, Francesca Tarchi, Matteo Ferraro, Giarita Merlino, Antonello Facchetti, Giorgio Rimoldi, Isabella Messori, Luigi Massai, Lara Int J Mol Sci Article 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. MDPI 2021-09-29 /pmc/articles/PMC8508948/ /pubmed/34638887 http://dx.doi.org/10.3390/ijms221910551 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sacco, Francesca
Tarchi, Matteo
Ferraro, Giarita
Merlino, Antonello
Facchetti, Giorgio
Rimoldi, Isabella
Messori, Luigi
Massai, Lara
Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands
title Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands
title_full Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands
title_fullStr Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands
title_full_unstemmed Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands
title_short Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands
title_sort reactions with proteins of three novel anticancer platinum(ii) complexes bearing n-heterocyclic ligands
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508948/
https://www.ncbi.nlm.nih.gov/pubmed/34638887
http://dx.doi.org/10.3390/ijms221910551
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