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001-es BibID:BIBFORM106923
035-os BibID:(Wos)000734253500001 (Scopus)85121990266
Első szerző:Cukierman, Daphne Schneider
Cím:Full Equilibrium Picture in Aqueous Binary and Ternary Systems Involving Copper(II), 1-Methylimidazole-Containing Hydrazonic Ligands, and the 103-112 Human Prion Protein Fragment / Daphne S. Cukierman, Nikolett Bodnár, Renata Diniz, Lajos Nagy, Csilla Kállay, Nicolás A. Rey
Dátum:2021
ISSN:0020-1669 1520-510X
Megjegyzések:In this work, we describe two novel 1-methylimidazole N-acylhydyrazonic ligands and their interaction with copper(II) in solution. Binary systems constituted by each of these hydrazones and the metal ion were studied by potentiometric titrations. The magnitude of their affinities for zinc(II) was also determined for the sake of comparison. Additionally, a full evaluation of the copper(II) chelation profile of the new ligands in ternary systems containing a human prion protein fragment was performed. Mixed ligand complexes comprising the HuPrP103?112 fragment, copper(II) ions, and an N-acylhydrazone were characterized by potentiometry, ultraviolet?visible spectroscopy, and circular dichroism. Some of these species were also identified by electrospray ionization mass spectrometry and unequivocally assigned through their isotopic distribution pattern. To the best of our knowledge, this is the first report concerning the stability of ternary complexes involving a hydrazonic metal?protein interaction modulator, copper, and a peptide. The ability of N-acylhydrazones to prevent peptide oxidation was also examined. Both ligands can partially prevent the formation of the doubly oxidized product, a process mediated by copper(II) ions. Oxidative stress is considered an important hallmark of neurodegenerative diseases such as prion-related spongiform encephalopathies. In this context, active intervention with respect to the deleterious copper-catalyzed methionine oxidation could represent an interesting therapeutic approach.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény hazai lapban
folyóiratcikk
Megjelenés:Inorganic Chemistry. - 61 : 1 (2021), p. 723-737. -
További szerzők:Bodnár Nikolett (1994-) (vegyész) Diniz, Renata Nagy Lajos (1979-) (vegyész) Kállay Csilla (1978-) (vegyész) Rey, Nicolas Adrian
Pályázati támogatás:NKFI-115480
OTKA
NKFI-128783
OTKA
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2.

001-es BibID:BIBFORM103444
035-os BibID:(Wos)000501026900008 (Scopus)85070294803
Első szerző:Cukierman, Daphne Schneider
Cím:Impact of pyridine-2-carboxaldehyde-derived aroylhydrazones on the copper-catalyzed oxidation of the M112A PrP103-112 mutant fragment / Daphne S. Cukierman, Nikolett Bodnár, Beatriz N. Evangelista, Lajos Nagy, Csilla Kállay, Nicolás A. Rey
Dátum:2019
ISSN:0949-8257
Megjegyzések:Misfolded prion protein (PrPSc) is known for its role in fatal neurodegenerative conditions, such as Creutzfeldt-Jakob disease. PrP fragments and their mutants represent important tools in the investigation of the neurotoxic mechanisms and in the evaluation of new compounds that can interfere with the processes involved in neuronal death. Metal-catalyzed oxidation of PrP has been implicated as a trigger for the conformational changes in protein structure, which, in turn, lead to misfolding. Targeting redox-active biometals copper and iron is relevant in the context of protection against the oxidation of biomolecules and the generation of oxidative stress, observed in several conditions and considered an event that might promote sporadic prion diseases as well as other neurodegenerative disorders. In this context, ortho-pyridine aroylhydrazones are of interest, as they can act as moderate tridentate ligands towards divalent metal ions such as copper(II). In the present work, we explore the potentiality of this chemical class as peptide protecting agents against the deleterious metal-catalyzed oxidation in the M112A mutant fragment of human PrP, which mimics relevant structural features that may play an important role in the neurotoxicity observed in prion pathologies. The compounds inhere studied, especially HPCFur, showed an improved stability in aqueous solution compared to our patented lead hydrazone INHHQ, displaying a very interesting protective effect toward the oxidation of methionine and histidine, processes that are related to both physiological and pathological aging.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Aroylhydrazones
Human prion protein
Copper(II)
Methionine oxidation
Oxidative stress
Megjelenés:Journal Of Biological Inorganic Chemistry. - 24 : 8 (2019), p. 1231-1244. -
További szerzők:Evangelista, Beatriz N. Rey, Nicolas Adrian Kállay Csilla (1978-) (vegyész) Bodnár Nikolett (1994-) (vegyész) Nagy Lajos (1979-) (vegyész)
Pályázati támogatás:NKFI-115480
Egyéb
NKFI-128783
Egyéb
GINOP-2.3.2-15-2016-00008
GINOP
UNKP-18-4
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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