Oxidative Activity of Copper Ions in Ternary Systems With N-Truncated Amyloid Beta Peptides and Low Molecular Weight Substances.

Oxidative stress is one of the most characteristic features of Alzheimer's disease. Previous studies revealed that copper complexes of amyloid beta (Aβ) peptides, mainly the Aβ form, could effectively catalyze the production of reactive oxygen species (ROS), causing the oxidation of physiological compounds. The Cu(II) binding to N-truncated Aβ forms containing His-2 and His-3 motifs produced less oxidative damage by arresting the Cu(II) ions in highly stable Cu(II)/Aβ complexes.

Multinuclear Silver(I)-Selenium Clusters Formation in Selenopeptides.

The reactions of ionic silver (Ag) with arginine vasopressin (AVP), a nonapeptide hormone cyclized by two cysteine residues, and its diselenium analogue was explored by an integrated LC-MS, UV-vis, and DFT approach. The replacement of Cys by SeCys in AVP increased the reactivity of the peptide toward Ag ions under mildly reducing conditions, with the formation of a SeAg cluster provided by Ag(I)-mediated dimerization of diselenide AVP. Specific electronic absorption bands confirmed the formation of the Agpeptide complex, supported by DFT calculations.

Distinct Aggregation Behavior of -Terminally Truncated Aβ Over Aβ in the Presence of Zn(II).

The deposition of amyloid-β (Aβ) aggregates and metal ions within senile plaques is a hallmark of Alzheimer's disease (AD). Among the modifications observed in Aβ peptides, -terminal truncation at Phe4, yielding Aβ, is highly prevalent in AD-affected brains and significantly alters Aβ's metal-binding and aggregation profiles. Despite the abundance of Zn(II) in senile plaques, its impact on the aggregation and toxicity of Aβ remains unexplored.

Nobody's Perfect: Choice of the Buffer and the Rate of Cu Ion-Peptide Interaction.

The choice of correct pH buffer is crucial in chemical studies modeling biological processes involving Cu ions. Popular buffers for physiological pH are known to form Cu(II) complexes, but their impact on kinetics of Cu(II) complexation has not been considered. We performed a stopped-flow kinetic study of Cu ion interactions with four popular buffers (phosphate, Tris, HEPES, and MOPS) and two buffers considered as nonbinding (MES and PIPPS).

The Cu(II) affinity constant and reactivity of Hepcidin-25, the main iron regulator in human blood.

Hepcidin is an iron regulatory hormone that does not bind iron directly. Instead, its mature 25-peptide form (H25) contains a binding site for other metals, the so-called ATCUN/NTS (amino-terminal Cu/Ni binding site). The Cu(II)-hepcidin complex was previously studied, but due to poor solubility and difficult handling of the peptide the definitive account on the binding equilibrium was not obtained reliably.

Zn(II) to Ag(I) Swap in Rad50 Zinc Hook Domain Leads to Interprotein Complex Disruption through the Formation of Highly Stable Ag(Cys) Cores.

The widespread application of silver nanoparticles in medicinal and daily life products increases the exposure to Ag(I) of thiol-rich biological environments, which help control the cellular metallome. A displacement of native metal cofactors from their cognate protein sites is a known phenomenon for carcinogenic and otherwise toxic metal ions. Here, we examined the interaction of Ag(I) with the peptide model of the interprotein zinc hook (Hk) domain of Rad50 protein from , a key player in DNA double-strand break (DSB) repair.

Reactive Cu2+-peptide intermediates revealed by kinetic studies gain relevance by matching time windows in copper metallomics.

The purpose of this essay is to propose that metallomic studies in the area of extracellular copper transport are incomplete without the explicit consideration of kinetics of Cu2+ion binding and exchange reactions. The kinetic data should be interpreted in the context of time constraints imposed by specific physiological processes. Examples from experimental studies of Cu2+ ion interactions with amino-terminal copper and nickel binding site/N-terminal site motifs are used to demonstrate that duration and periodicity of such processes as bloodstream transport or neurotransmission promote the reaction intermediates to the role of physiological effectors.

Corrigendum: Ni-assisted hydrolysis may affect the human proteome; filaggrin degradation as an example of possible consequences.

[This corrects the article DOI: 10.3389/fmolb.2022.

An Overlooked Hepcidin-Cadmium Connection.

Hepcidin (DTHFPICIFCCGCCHRSKCGMCCKT), an iron-regulatory hormone, is a 25-amino-acid peptide with four intramolecular disulfide bonds circulating in blood. Its hormonal activity is indirect and consists of marking ferroportin-1 (an iron exporter) for degradation. Hepcidin biosynthesis involves the N-terminally extended precursors prepro-hepcidin and pro-hepcidin, processed by peptidases to the final 25-peptide form.

Dual mode of voltammetric studies on Cu(II) complexes of His2 peptides: phosphate and peptide sequence recognition.

Copper(II) complexes of peptides with a histidine residue at the second position (His2 peptides) provide a unique profile of electrochemical behavior, offering signals of both Cu(II) reduction and Cu(II) oxidation. Furthermore, their structures with vacant positions in the equatorial coordination plane could facilitate interactions with other biomolecules. In this work, we designed a library of His2 peptides based on the sequence of Aβ (RHDSG), an amyloid beta peptide derivative.

Ni(II) Ions May Target the Entire Melatonin Biosynthesis Pathway-A Plausible Mechanism of Nickel Toxicity.

Nickel is toxic to humans. Its compounds are carcinogenic. Furthermore, nickel allergy is a severe health problem that affects approximately 10-20% of humans.

Interactions of neurokinin B with copper(II) ions and their potential biological consequences.

Preeclampsia is a blood pressure disorder associated with significant proteinuria. Hypertensive women have increased levels of neurokinin B (NKB) and Cu(II) ions in blood plasma during pregnancy. NKB bears the ATCUN/NTS N-terminal motif empowering strong Cu(II) binding in a characteristic four-nitrogen (4N) square-planar motif, but an alternative Cu(II)NKB geometry was proposed earlier.

Covalent Proximity Scanning of a Distal Cysteine to Target PI3Kα.

Covalent protein kinase inhibitors exploit currently noncatalytic cysteines in the adenosine 5'-triphosphate (ATP)-binding site via electrophiles directly appended to a reversible-inhibitor scaffold. Here, we delineate a path to target solvent-exposed cysteines at a distance >10 Å from an ATP-site-directed core module and produce potent covalent phosphoinositide 3-kinase α (PI3Kα) inhibitors. First, reactive warheads are used to reach out to Cys862 on PI3Kα, and second, enones are replaced with druglike warheads while linkers are optimized.

Structures of Silver Fingers and a Pathway to Their Genotoxicity.

Recently, we demonstrated that Ag can directly replace Zn in zinc fingers (ZFs). The cooperative binding of Ag to ZFs leads to a thermodynamically irreversible formation of silver clusters destroying the native ZF structure. Thus, a reported loss of biological function of ZF proteins is a likely consequence of such replacement.

Kinetics of Cu(II) complexation by ATCUN/NTS and related peptides: a gold mine of novel ideas for copper biology.

Cu(II)-peptide complexes are intensely studied as models for biological peptides and proteins and for their direct importance in copper homeostasis and dyshomeostasis in human diseases. In particular, high-affinity ATCUN/NTS (amino-terminal copper and nickel/N-terminal site) motifs present in proteins and peptides are considered as Cu(II) transport agents for copper delivery to cells. The information on the affinities and structures of such complexes derived from steady-state methods appears to be insufficient to resolve the mechanisms of copper trafficking, while kinetic studies have recently shown promise in explaining them.

Intermediate Cu(II)-Thiolate Species in the Reduction of Cu(II)GHK by Glutathione: A Handy Chelate for Biological Cu(II) Reduction.

Gly-His-Lys (GHK) is a tripeptide present in the human bloodstream that exhibits a number of biological functions. Its activity is attributed to the copper-complexed form, Cu(II)GHK. Little is known, however, about the molecular aspects of the mechanism of its action.