Methionine oxidation of amyloid peptides by peroxovanadium complexes: inhibition of fibril formation through a distinct mechanism

Abstract

Fibril formation of amyloid peptides is linked to a number of pathological states. The prion protein (PrP) and amyloid-β (Aβ) are two remarkable examples that are correlated with prion disorders and Alzheimer's disease, respectively. Metal complexes, such as those formed by platinum and ruthenium compounds, can act as inhibitors against peptide aggregation primarily through metal coordination. This study revealed the inhibitory effect of two peroxovanadium complexes, (NH4)[VO(O2)2(bipy)]·4H2O (1) and (NH4)[VO(O2)2(phen)]·2H2O (2), on amyloid fibril formation of PrP106-126 and Aβ1-42via site-specific oxidation of methionine residues, besides direct binding of the complexes with the peptides. Complexes 1 and 2 showed higher anti-amyloidogenic activity on PrP106-126 aggregation than on Aβ1-42, though their regulation on the cytotoxicity induced by the two peptides could not be differentiated. The action efficacy may be attributed to the different molecular structures of the vanadium complex and the peptide sequence. Results reflected that methionine oxidation may be a crucial action mode in inhibiting amyloid fibril formation. This study offers a possible application value for peroxovanadium complexes against amyloid proteins.

A catalytic antioxidant for limiting amyloid-beta peptide aggregation and reactive oxygen species generation

“…In addition, a number of groups have explored the use of discrete metal complexes for the diagnosis and treatment of AD 20. In terms of therapeutics, Pt,21 Ru,22 Ir,23 Co,10b,24 Re,25 Rh,26 Mn,27 and V28 complexes have been investigated for their ability to modify the aggregation of the Aβ peptide, and certain compounds have shown promising results in disease models. For example, an orally-available Pt( iv ) complex (Scheme 1) was shown to cross the blood–brain barrier (BBB), reduce plaque burden, and reduce Aβ peptide levels in a APP/Ps1 mouse model 29.…”

Modification of Aβ Peptide Aggregation via Covalent Binding of a Series of Ru(III) Complexes

“…A number of Pt (Barnham et al, 2008;Sasaki et al, 2012;Collin et al, 2013;Streltsov et al, 2013), Ru (Valensin et al, 2010;Messori et al, 2013;Jones et al, 2015), Co (Suh et al, 2007;Heffern et al, 2014;Derrick et al, 2017), and V (He et al, 2015) metal complexes have shown promise in interacting with the Aβ peptide and modifying its aggregation. For example, a series of Pt(II) phenanthroline complexes (Chart 1) were shown to bind to the peptide, modulating the aggregation and the neurotoxicity of Aβ (Barnham et al, 2008).…”

Methionine one-electron oxidation: Coherent contributions from radiolysis, IRMPD spectroscopy, DFT calculations and electrochemistry

“…Methionine oxidation is an important event. It plays roles in fibrillation of -amyloid peptide and -synuclein, and thus in Alzheimer's [45,46] and Parkinson's diseases [47,48]. Methionine sulfoxide is among the rare oxidized forms that can be repaired.…”