Utilizing NMR and EPR spectroscopy to probe the role of copper in prion diseases

Emwas, Abdul‐Hamid; Al‐Talla, Zeyad A.; Guo, Xin; Al-Ghamdi, Suliman; Al‐Masri, Harbi Tomah

doi:10.1002/mrc.3936

Cited by 35 publications

(29 citation statements)

References 292 publications

(492 reference statements)

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“…[72,74,89,90,[93][94][95][96][97][98][109][110][111] Structural rearrangement of the N-terminus caused by copper(II) binding has also been studied but conflicting results have been reported for peptides that contain different domains. [112,113] The majority of studies with PrP peptide fragments allowed the assessment of the copper(II) coordination modes, but the results represented a simplified model of the copper-binding chemistry and did not consider important aspects of the metal-PrP interactions because protein folding and interregion interactions were not accounted for. Some studies involved peptides that encompassed both the octarepeat region and the fifth binding site, [91,102] as well as a recombinant mouse strain of PrP and a battery of mutants of the N-terminal region, [114] contributed to understanding the complex relationships between PrP and copper.…”

Section: Resultsmentioning

confidence: 99%

“…Metal binding to His111 is further supported by limited proteolysis experiments with trypsin, for which copper(II) has no reported effect on enzyme activity. [104] Three peptide fragments were produced after complete trypsin digestion of AcPrP [ Figure 1], namely, AcPr(P60-106), PrP (107)(108)(109)(110) and PrP (111)(112)(113)(114) [Figure 8 a]. In the absence of Cu 2+ , the peptide was digested after 30 min.…”

Section: Proteolysis Of Acprp(60-114) Modulated By Copper(ii)mentioning

confidence: 99%

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Cross‐Talk Between the Octarepeat Domain and the Fifth Binding Site of Prion Protein Driven by the Interaction of Copper(II) with the N‐terminus

Natale

Turi

Pappalardo

et al. 2015

Chemistry A European J

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Prion diseases are a group of neurodegenerative diseases based on the conformational conversion of the normal form of the prion protein (PrP(C)) to the disease-related scrapie isoform (PrP(Sc)). Copper(II) coordination to PrP(C) has attracted considerable interest for almost 20 years, mainly due to the possibility that such an interaction would be an important event for the physiological function of PrP(C). In this work, we report the copper(II) coordination features of the peptide fragment Ac(PEG11)3PrP(60-114) [Ac = acetyl] as a model for the whole N-terminus of the PrP(C) metal-binding domain. We studied the complexation properties of the peptide by means of potentiometric, UV/Vis, circular dichroism and electrospray ionisation mass spectrometry techniques. The results revealed that the preferred histidyl binding sites largely depend on the pH and copper(II)/peptide ratio. Formation of macrochelate species occurs up to a 2:1 metal/peptide ratio in the physiological pH range and simultaneously involves the histidyl residues present both inside and outside the octarepeat domain. However, at increased copper(II)/peptide ratios amide-bound species form, especially within the octarepeat domain. On the contrary, at basic pH the amide-bound species predominate at any copper/peptide ratio and are formed preferably with the binding sites of His96 and His111, which is similar to the metal-binding-affinity order observed in our previous studies.

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Section: Resultsmentioning

confidence: 99%

Section: Proteolysis Of Acprp(60-114) Modulated By Copper(ii)mentioning

confidence: 99%

Cross‐Talk Between the Octarepeat Domain and the Fifth Binding Site of Prion Protein Driven by the Interaction of Copper(II) with the N‐terminus

Natale

Turi

Pappalardo

et al. 2015

Chemistry A European J

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“…To begin with, we investigated the possible doping effect of Zn(C 6 F 5 ) 2 using electron paramagnetic resonance (EPR) spectroscopy . EPR has been used successfully to study organic‐free radicals and transition metals, as well as detect Lewis acid‐induced doping in semiconductors . For this experiment, we chose a blend consisting of C 8 ‐BTBT and C 16 IDT‐BT because in our earlier work it showed the highest hole mobility values enabled upon doping with B(C 6 F 5 ) 3 .…”

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confidence: 99%

Addition of the Lewis Acid Zn(C₆F₅)₂ Enables Organic Transistors with a Maximum Hole Mobility in Excess of 20 cm² V⁻¹ s⁻¹

Paterson

Tsetseris

et al. 2019

Advanced Materials

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The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201900871.Incorporating the molecular organic Lewis acid tris(pentafluorophenyl)borane [B(C 6 F 5 ) 3 ] into organic semiconductors has shown remarkable promise in recent years for controlling the operating characteristics and performance of various opto/electronic devices, including, light-emitting diodes, solar cells, and organic thin-film transistors (OTFTs). Despite the demonstrated potential, however, to date most of the work has been limited to B(C 6 F 5 ) 3 with the latter serving as the prototypical air-stable molecular Lewis acid system. Herein, the use of bis(pentafluorophenyl)zinc [Zn(C 6 F 5 ) 2 ] is reported as an alternative Lewis acid additive in high-hole-mobility OTFTs based on small-molecule:polymer blends comprising 2,7-dioctyl[1]benzothieno [3,2-b][1]benzothiophene and indacenodithiophene-benzothiadiazole. Systematic analysis of the materials and device characteristics supports the hypothesis that Zn(C 6 F 5 ) 2 acts simultaneously as a p-dopant and a microstructure modifier.It is proposed that it is the combination of these synergistic effects that leads to OTFTs with a maximum hole mobility value of 21.5 cm 2 V −1 s −1 . The work not only highlights Zn(C 6 F 5 ) 2 as a promising new additive for next-generation optoelectronic devices, but also opens up new avenues in the search for high-mobility organic semiconductors.

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“…This suggests that PrP is a target of copper-catalyzed oxidation and that this reaction leads to profound structural changes in the protein. Oxidation therefore must be taken into account as a potential side reaction when considering the role of copper in prion disease [52,53,202,203].…”

Section: Copper Ions In Nervous System Development and Neurodegeneratmentioning

confidence: 99%

Using NMR spectroscopy to investigate the role played by copper in prion diseases

et al. 2020

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Prion diseases are a group of rare neurodegenerative disorders that develop as a result of the conformational conversion of normal prion protein (PrP C) to the disease-associated isoform (PrP Sc). The mechanism that actually causes disease remains unclear. However, the mechanism underlying the conformational transformation of prion protein is partially understood-in particular, there is strong evidence that copper ions play a significant functional role in prion proteins and in their conformational conversion. Various models of the interaction of copper ions with prion proteins have been proposed for the Cu (II)-binding, cell-surface glycoprotein known as prion protein (PrP). Changes in the concentration of copper ions in the brain have been associated with prion diseases and there is strong evidence that copper plays a significant functional role in the conformational conversion of PrP. Nevertheless, because copper ions have been shown to have both a positive and negative effect on prion disease onset, the role played by Cu (II) ions in these diseases remains a topic of debate. Because of the unique properties of paramagnetic Cu (II) ions in the magnetic field, their interactions with PrP can be tracked even at single atom resolution using nuclear magnetic resonance (NMR) spectroscopy. Various NMR approaches have been utilized to study the kinetic, thermodynamic, and structural properties of Cu (II)-PrP interactions. Here, we highlight the different models of copper interactions with PrP with particular focus on studies that use NMR spectroscopy to investigate the role played by copper ions in prion diseases.

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Utilizing NMR and EPR spectroscopy to probe the role of copper in prion diseases

Cited by 35 publications

References 292 publications

Cross‐Talk Between the Octarepeat Domain and the Fifth Binding Site of Prion Protein Driven by the Interaction of Copper(II) with the N‐terminus

Cross‐Talk Between the Octarepeat Domain and the Fifth Binding Site of Prion Protein Driven by the Interaction of Copper(II) with the N‐terminus

Addition of the Lewis Acid Zn(C₆F₅)₂ Enables Organic Transistors with a Maximum Hole Mobility in Excess of 20 cm² V⁻¹ s⁻¹

Using NMR spectroscopy to investigate the role played by copper in prion diseases

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Utilizing NMR and EPR spectroscopy to probe the role of copper in prion diseases

Cited by 35 publications

References 292 publications

Cross‐Talk Between the Octarepeat Domain and the Fifth Binding Site of Prion Protein Driven by the Interaction of Copper(II) with the N‐terminus

Cross‐Talk Between the Octarepeat Domain and the Fifth Binding Site of Prion Protein Driven by the Interaction of Copper(II) with the N‐terminus

Addition of the Lewis Acid Zn(C6F5)2 Enables Organic Transistors with a Maximum Hole Mobility in Excess of 20 cm2 V−1 s−1

Using NMR spectroscopy to investigate the role played by copper in prion diseases

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Addition of the Lewis Acid Zn(C₆F₅)₂ Enables Organic Transistors with a Maximum Hole Mobility in Excess of 20 cm² V⁻¹ s⁻¹