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Special Issue "Interaction between Metal Compounds and Proteins"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 15 June 2019

Special Issue Editor

Guest Editor
Prof. Antonello Merlino

Department of Chemical Sciences, University of Naples Federico II, Napoli, Italy
Website | E-Mail
Interests: protein–metal-based drug adducts; X-Ray crystallography; protein metalation; protein–ligand interactions

Special Issue Information

Dear colleagues,

The binding of metal compounds to proteins plays a major role in many different fields of chemistry, from drug delivery to catalysis, from the biotechnological applications of natural and synthetic metalloenzymes to the definition of the pharmacological profiles of drugs. Here, we plan to collect original research articles, short communications, or review articles describing recent advances in the field of the characterization of the interactions between proteins and metal compounds, including metal nanoparticles.

Potential topics include, but are not limited to, the following:

Mechanistic studies of the protein metalation process

Analytical advances in the identification of protein targets for metallodrugs

Analytical advances in the determination of protein–metal recognition binding sites

Structural data on the formation of protein–metal adducts and protein–metal complexes

Identification of metal binding sites on protein structures

Biophysical studies of the interactions between proteins and metal nanoclusters/nanoparticles

Prof. Antonello Merlino
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Protein–metal adducts
  • Protein metalation
  • Protein–metal nanoparticle interactions
  • Metal binding sites
  • Metallomics
  • Organometallic compounds
  • Metal-based drugs
  • Metalloenzymes

Published Papers (5 papers)

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Research

Open AccessArticle Studies on the Interaction between Poly-Phosphane Gold(I) Complexes and Dihydrofolate Reductase: An Interplay with Nicotinamide Adenine Dinucleotide Cofactor
Int. J. Mol. Sci. 2019, 20(7), 1802; https://doi.org/10.3390/ijms20071802
Received: 18 March 2019 / Revised: 8 April 2019 / Accepted: 9 April 2019 / Published: 11 April 2019
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Abstract
A class of gold(I) phosphane complexes have been identified as inhibitors of dihydrofolate reductase (DHFR) from E. coli, an enzyme that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), using NADPH as a coenzyme. In this work, to comprehend the nature [...] Read more.
A class of gold(I) phosphane complexes have been identified as inhibitors of dihydrofolate reductase (DHFR) from E. coli, an enzyme that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), using NADPH as a coenzyme. In this work, to comprehend the nature of the interaction at the basis of these inhibitory effects, the binding properties of bis- and tris-phosphane gold(I) chloride compounds in regards to DHFR have been studied by emission spectroscopy and spectrophotometric assays. The lack of cysteine and seleno-cysteine residues in the enzyme active site, the most favorable sites of attack of Au(I) moieties, makes this work noteworthy. The interaction with the gold compounds results into the quenching of the DHFR tryptophan’s emissions and in an enhancement of their intrinsic emission intensities. Moreover, a modulating action of NADPH is highlighted by means of an increase of the gold compound affinity toward the enzyme; in fact, the dissociation constants calculated for the interactions between DHFR and each gold compound in the presence of saturating NADPH were lower than the ones observed for the apo-enzyme. The fluorimetric data afforded to Kd values ranged from 2.22 ± 0.25 µM for (PPh3)2AuCl in the presence of NADPH to 21.4 ± 3.85 µM for 4L3AuTf in the absence of NADPH. By elucidating the energetic aspects of the binding events, we have attempted to dissect the role played by the gold phosphane/protein interactions in the inhibitory activity, resulting in an exothermic enthalpy change and a positive entropic contribution (ΔH° = −5.04 ± 0.08 kcal/mol and ΔS° = 7.34 ± 0.005 cal/mol·K). Full article
(This article belongs to the Special Issue Interaction between Metal Compounds and Proteins)
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Open AccessArticle Platinum(II) O,S Complexes Inhibit the Aggregation of Amyloid Model Systems
Int. J. Mol. Sci. 2019, 20(4), 829; https://doi.org/10.3390/ijms20040829
Received: 11 January 2019 / Revised: 8 February 2019 / Accepted: 13 February 2019 / Published: 14 February 2019
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Abstract
Platinum(II) complexes with different cinnamic acid derivatives as ligands were investigated for their ability to inhibit the aggregation process of amyloid systems derived from Aβ, Yeast Prion Protein Sup35p and the C-terminal domain of nucleophosmin 1. Thioflavin T binding assays and circular dichroism [...] Read more.
Platinum(II) complexes with different cinnamic acid derivatives as ligands were investigated for their ability to inhibit the aggregation process of amyloid systems derived from Aβ, Yeast Prion Protein Sup35p and the C-terminal domain of nucleophosmin 1. Thioflavin T binding assays and circular dichroism data indicate that these compounds strongly inhibit the aggregation of investigated peptides exhibiting IC50 values in the micromolar range. MS analysis confirms the formation of adducts between peptides and Pt(II) complexes that are also able to reduce amyloid cytotoxicity in human SH-SY5Y neuroblastoma cells. Overall data suggests that bidentate ligands based on β-hydroxy dithiocinnamic esters can be used to develop platinum or platinoid compounds with anti-amyloid aggregation properties. Full article
(This article belongs to the Special Issue Interaction between Metal Compounds and Proteins)
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Open AccessArticle Reactivity of Gold(I) Monocarbene Complexes with Protein Targets: A Theoretical Study
Int. J. Mol. Sci. 2019, 20(4), 820; https://doi.org/10.3390/ijms20040820
Received: 15 January 2019 / Revised: 6 February 2019 / Accepted: 12 February 2019 / Published: 14 February 2019
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Abstract
Neutral N–heterocyclic carbene gold(I) compounds such as IMeAuCl are widely used both in homogeneous catalysis and, more recently, in medicinal chemistry as promising antitumor agents. In order to shed light on their reactivity with protein side chains, we have carried out density functional [...] Read more.
Neutral N–heterocyclic carbene gold(I) compounds such as IMeAuCl are widely used both in homogeneous catalysis and, more recently, in medicinal chemistry as promising antitumor agents. In order to shed light on their reactivity with protein side chains, we have carried out density functional theory (DFT) calculations on the thermodynamics and kinetics of their reactions with water and various nucleophiles as a model of plausible protein binding sites such as arginine, aspartic acid, asparagine, cysteine, glutamic acid, glutamine, histidine, lysine, methionine, selenocysteine, and the N-terminal group. In agreement with recent experimental data, our results suggest that IMeAuCl easily interacts with all considered biological targets before being hydrated—unless sterically prevented—and allows the establishment of an order of thermodynamic stability and of kinetic reactivity for its binding to protein residues. Full article
(This article belongs to the Special Issue Interaction between Metal Compounds and Proteins)
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Open AccessArticle Reaction with Proteins of a Five-Coordinate Platinum(II) Compound
Int. J. Mol. Sci. 2019, 20(3), 520; https://doi.org/10.3390/ijms20030520
Received: 10 December 2018 / Revised: 21 January 2019 / Accepted: 23 January 2019 / Published: 26 January 2019
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Abstract
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 = [...] Read more.
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. Full article
(This article belongs to the Special Issue Interaction between Metal Compounds and Proteins)
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Open AccessArticle Copper Binding Features of Tropomyosin-Receptor-Kinase-A Fragment: Clue for Neurotrophic Factors and Metals Link
Int. J. Mol. Sci. 2018, 19(8), 2374; https://doi.org/10.3390/ijms19082374
Received: 30 June 2018 / Revised: 1 August 2018 / Accepted: 7 August 2018 / Published: 12 August 2018
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Abstract
The nerve growth factor (NGF) is a neurotrophin essential for the development and maintenance of neurons, whose activity is influenced by copper ions. The NGF protein exerts its action by binding to its specific receptor, TrkA. In this study, a specific domain of [...] Read more.
The nerve growth factor (NGF) is a neurotrophin essential for the development and maintenance of neurons, whose activity is influenced by copper ions. The NGF protein exerts its action by binding to its specific receptor, TrkA. In this study, a specific domain of the TrkA receptor, region 58–64, was synthesized and its copper(II) complexes characterized by means of potentiometric and spectroscopic studies. The two vicinal histidine residues provide excellent metal anchoring sites and, at physiological pH, a complex with the involvement of the peptide backbone amide nitrogen is the predominant species. The TrkA peptide is competitive for metal binding with analogous peptides due to the N-terminal domain of NGF. These data provide cues for future exploration of the effect of metal ions on the activity of the NGF and its specific cellular receptor. Full article
(This article belongs to the Special Issue Interaction between Metal Compounds and Proteins)
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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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