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Reaction with Proteins of a Five-Coordinate Platinum(II) Compound

Stable five-coordinate Pt(II) complexes have been highlighted as a promising and original platform for the development of new cytotoxic drugs. Their interaction with proteins has been scarcely studied. Here, the reactivity of the five-coordinate Pt(II) compound [Pt(I)(Me) (dmphen)(olefin)] (Me = met...

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Autores principales: Ferraro, Giarita, Marzo, Tiziano, Cucciolito, Maria Elena, Ruffo, Francesco, Messori, Luigi, Merlino, Antonello
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387405/
https://www.ncbi.nlm.nih.gov/pubmed/30691130
http://dx.doi.org/10.3390/ijms20030520
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author Ferraro, Giarita
Marzo, Tiziano
Cucciolito, Maria Elena
Ruffo, Francesco
Messori, Luigi
Merlino, Antonello
author_facet Ferraro, Giarita
Marzo, Tiziano
Cucciolito, Maria Elena
Ruffo, Francesco
Messori, Luigi
Merlino, Antonello
author_sort Ferraro, Giarita
collection PubMed
description Stable five-coordinate Pt(II) complexes have been highlighted as a promising and original platform for the development of new cytotoxic drugs. Their interaction with proteins has been scarcely studied. Here, the reactivity of the five-coordinate Pt(II) compound [Pt(I)(Me) (dmphen)(olefin)] (Me = methyl, dmphen = 2,9-dimethyl-1,10-phenanthroline, olefin = dimethylfumarate) with the model proteins hen egg white lysozyme (HEWL) and bovine pancreatic ribonuclease (RNase A) has been investigated by X-ray crystallography and electrospray ionization mass spectrometry. The X-ray structures of the adducts of RNase A and HEWL with [Pt(I)(Me)(dmphen)(olefin)] are not of very high quality, but overall data indicate that, upon reaction with RNase A, the compound coordinates the side chain of His105 upon releasing the iodide ligand, but retains the pentacoordination. On the contrary, upon reaction with HEWL, the trigonal bi-pyramidal Pt geometry is lost, the iodide and the olefin ligands are released, and the metal center coordinates the side chain of His15 probably adopting a nearly square-planar geometry. This work underlines the importance of the combined use of crystallographic and mass spectrometry techniques to characterize, in detail, the protein–metallodrug recognition process. Our findings also suggest that five-coordinate Pt(II) complexes can act either retaining their uncommon structure or functioning as prodrugs, i.e., releasing square-planar platinum complexes as bioactive species.
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spelling pubmed-63874052019-02-27 Reaction with Proteins of a Five-Coordinate Platinum(II) Compound Ferraro, Giarita Marzo, Tiziano Cucciolito, Maria Elena Ruffo, Francesco Messori, Luigi Merlino, Antonello Int J Mol Sci Article Stable five-coordinate Pt(II) complexes have been highlighted as a promising and original platform for the development of new cytotoxic drugs. Their interaction with proteins has been scarcely studied. Here, the reactivity of the five-coordinate Pt(II) compound [Pt(I)(Me) (dmphen)(olefin)] (Me = methyl, dmphen = 2,9-dimethyl-1,10-phenanthroline, olefin = dimethylfumarate) with the model proteins hen egg white lysozyme (HEWL) and bovine pancreatic ribonuclease (RNase A) has been investigated by X-ray crystallography and electrospray ionization mass spectrometry. The X-ray structures of the adducts of RNase A and HEWL with [Pt(I)(Me)(dmphen)(olefin)] are not of very high quality, but overall data indicate that, upon reaction with RNase A, the compound coordinates the side chain of His105 upon releasing the iodide ligand, but retains the pentacoordination. On the contrary, upon reaction with HEWL, the trigonal bi-pyramidal Pt geometry is lost, the iodide and the olefin ligands are released, and the metal center coordinates the side chain of His15 probably adopting a nearly square-planar geometry. This work underlines the importance of the combined use of crystallographic and mass spectrometry techniques to characterize, in detail, the protein–metallodrug recognition process. Our findings also suggest that five-coordinate Pt(II) complexes can act either retaining their uncommon structure or functioning as prodrugs, i.e., releasing square-planar platinum complexes as bioactive species. MDPI 2019-01-26 /pmc/articles/PMC6387405/ /pubmed/30691130 http://dx.doi.org/10.3390/ijms20030520 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ferraro, Giarita
Marzo, Tiziano
Cucciolito, Maria Elena
Ruffo, Francesco
Messori, Luigi
Merlino, Antonello
Reaction with Proteins of a Five-Coordinate Platinum(II) Compound
title Reaction with Proteins of a Five-Coordinate Platinum(II) Compound
title_full Reaction with Proteins of a Five-Coordinate Platinum(II) Compound
title_fullStr Reaction with Proteins of a Five-Coordinate Platinum(II) Compound
title_full_unstemmed Reaction with Proteins of a Five-Coordinate Platinum(II) Compound
title_short Reaction with Proteins of a Five-Coordinate Platinum(II) Compound
title_sort reaction with proteins of a five-coordinate platinum(ii) compound
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387405/
https://www.ncbi.nlm.nih.gov/pubmed/30691130
http://dx.doi.org/10.3390/ijms20030520
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