Coordination and Metal Ion-Catalyzed Oxidation of a Mutated Prion Protein Fragment.
4 affiliations
- 1Department of Inorganic and Analytical Chemistry University of Debrecen H-4032 Debrecen Hungary unideb.hu.
- 2Department of Applied Chemistry University of Debrecen H-4032 Debrecen Hungary unideb.hu.
- 3Faculty of Chemistry University of Wrocław Fryderyka Joliot-Curie 14, 50-383 Wrocław Poland uni.wroc.pl.
- 4Centre for Structural Science Research Centre for Natural Sciences Hungarian Research Network (HUN-REN) Magyar Tudósok Körútja 2, H-1117 Budapest Hungary ttk.hu.
Abstract
Metal ion coordination and metal-catalyzed oxidative processes play a key role in the pathology of neurodegenerative diseases involving prion protein peptide. In this work, the complex formation and copper(II)-catalyzed oxidation of a prion protein-derived model peptide, H₂N-GTHSAKHA-NH₂, were investigated. Complex formation with Cu(II), Ni(II), and Zn(II) ions was studied by pH-potentiometry, UV-vis, EPR, and circular dichroism spectroscopy. The results demonstrate the formation of mono- and dinuclear complexes, with a strong preference for albumin-like N-terminal coordination involving the amino group, deprotonated amide nitrogen atoms, and histidine imidazole donors. Copper(II) dominates at the N-terminal site also in mixed-metal systems, whereas nickel(II) and zinc(II) bind only to secondary C-terminal sites. HPLC and LC-MS studies revealed that treatment with the Cu/H₂O₂ system selectively oxidized the C-terminal histidine residue, yielding 2-oxo-histidine. The effects of potential antioxidants on this oxidation process were also investigated. The addition of ascorbic acid significantly enhanced reactive oxygen species generation, resulting in increased peptide oxidation and DNA degradation, whereas the salan-based Salpyran ligand inhibited oxidation.
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BibTeX
@article{galvacsi2026coordination,
title = {{Coordination and Metal Ion-Catalyzed Oxidation of a Mutated Prion Protein Fragment.}},
author = {Antal Galvácsi and Roland Császár and Lajos Nagy and Monika Katarzyna Lesiów and Nóra V May and Csilla Kállay},
journal = {Bioinorganic chemistry and applications},
year = {2026},
month = oct,
doi = {10.1155/bca/8800140},
url = {https://europepmc.org/article/MED/42923590},
note = {CC BY},
}
RIS
TY - JOUR
TI - Coordination and Metal Ion-Catalyzed Oxidation of a Mutated Prion Protein Fragment.
AU - Antal Galvácsi
AU - Roland Császár
AU - Lajos Nagy
AU - Monika Katarzyna Lesiów
AU - Nóra V May
AU - Csilla Kállay
PY - 2026
DA - 2026/10/21
JO - Bioinorganic chemistry and applications
DO - 10.1155/bca/8800140
UR - https://europepmc.org/article/MED/42923590
AB - Metal ion coordination and metal-catalyzed oxidative processes play a key role in the pathology of neurodegenerative diseases involving prion protein peptide. In this work, the complex formation and copper(II)-catalyzed oxidation of a prion protein-derived model peptide, H₂N-GTHSAKHA-NH₂, were investigated. Complex formation with Cu(II), Ni(II), and Zn(II) ions was studied by pH-potentiometry, UV-vis, EPR, and circular dichroism spectroscopy. The results demonstrate the formation of mono- and dinuclear complexes, with a strong preference for albumin-like N-terminal coordination involving the amino group, deprotonated amide nitrogen atoms, and histidine imidazole donors. Copper(II) dominates at the N-terminal site also in mixed-metal systems, whereas nickel(II) and zinc(II) bind only to secondary C-terminal sites. HPLC and LC-MS studies revealed that treatment with the Cu/H₂O₂ system selectively oxidized the C-terminal histidine residue, yielding 2-oxo-histidine. The effects of potential antioxidants on this oxidation process were also investigated. The addition of ascorbic acid significantly enhanced reactive oxygen species generation, resulting in increased peptide oxidation and DNA degradation, whereas the salan-based Salpyran ligand inhibited oxidation.
SN - 1565-3633
SN - 1687-479X
ER -