Abstract The redox activity of Cu ions bound to the amyloid-β (Aβ) peptide is implicated as a source of oxidative stress in the context of Alzheimer's disease. In order to explain the efficient redox cycling between Cu(II)-Aβ (distorted square pyramidal) and Cu(I)-Aβ (digonal) resting states, the…
Abstract The progressive, neurodegenerative Alzheimer's disease (AD) is the most widespread dementia. Due to the ageing of the population and the current lack of molecules able to prevent or stop the disease, AD will be even more impactful for society in the future. AD is a multifactorial disease,…
Abstract Copper (Cu) in its ionic forms is an essential element for mammals and its homeostasis is tightly controlled. Accordingly, Cu-dyshomeostasis can be lethal as is the case in the well-established genetic Wilson's and Menkes diseases. In Alzheimer's disease (AD), Cu-accumulation occurs in…
Abstract Glutathione (GSH) is the most abundant thiol in mammalian cells and plays a crucial role in maintaining redox cellular homeostasis. The thiols of two GSH molecules can be oxidized to the disulfide GSSG. The cytosolic GSH/GSSG ratio is very high (>100), and its reduction can lead to…
Abstract The measurement of labile CuII in biological samples is fundamental for understanding Cu metabolism and has been emerging as a promising diagnostic marker for Cu-related pathologies such as Wilson's and Alzheimer's diseases. The use of fluorescent chelators may be useful to circumvent…
Abstract Depending on the coordination, copper ions can have a very high activity in catalyzing the production of reactive oxygen species. Thus interest arose in increasing the activity of antimicrobial peptides (AMPs) by equipping them with a Cu-binding unit. Several examples, native and…
Abstract Copper (Cu) is an essential micronutrient for most organisms and serves mainly as a redox-active catalytic centre in enzymes cycling between Cu+ and Cu2+. Membrane transporters and shuttles are involved to bring and insert Cu into these enzymes and to control tightly the copper…
Abstract Employing peptide-based models of copper transporter 1 (CTR1), we show that the trimeric arrangement of its N-terminus tunes its reactivity with Cu, promoting Cu(II) reduction and stabilizing Cu(I). Hence, the employed multimeric models of CTR1 provide an important contribution to studies…
Abstract The measurement of exchangeable Cu2+ levels in biological samples is gaining interest in the context of copper-related pathologies. Here, we report a Tb3+ luminescent turn-off sensor for Cu2+ based on the specific and suitable-affinity Xxx-Zzz-His (ATCUN) peptide motif, enabling Cu2+…
Abstract Copper-complexes are of medicinal and biological interest, including as anticancer drugs designed to cleave intracellular biomolecules via O2 activation. To exhibit such activity, the copper complex must be redox-active and resistant to dissociation. Metallothioneins (MTs) and glutathione…
Abstract Mounting evidence supports the role of amyloidogenesis, oxidative stress, and metal dyshomeostasis in the development of neurodegenerative disorders. Parkinson's Disease is characterized by α-Synuclein (αSyn) accumulation and aggregation in brain regions, also promoted by Cu2+. αSyn is…
Abstract Reversible turn-on fluorescent sensors of Cu(II) are of high interest for biological studies. We re-investigate a reported sensor, showing that turn-on occurs via irreversible Cu(II)-induced sensor oxidation only in the presence of acetonitrile. This prevents its application in biological…
Abstract Copper(II) forms well-known and stable complexes with peptides having histidine at position 2 (Xxx-His) or 3 (Xxx-Zzz-His). Their properties differ considerably due to the histidine positioning. Here we report that in the hybrid motif Xxx-His-His, the Cu(II)-complexes can be switched…
Abstract It was shown that His3 of human copper transporter 1 (hCtr1) prompts the ATCUN-like Cu(II) coordination for model peptides of the hCtr1 N-terminus. Its high Cu(II) affinity is a potential driving force for the transfer of Cu(II) from extracellular Cu(II) carriers to hCtr1. Having a…
Summary Thiosemicarbazones (TSCs) are a class of strong metal ion ligands, which are currently being investigated for several applications, such as anticancer treatment. In addition to these ligands only, which exert their activity upon interaction with metal ions in cells, preformed metal–TSC…
