Designed Metal-ATCUN Derivatives: Redox- and Non-redox-Based Applications Relevant for Chemistry, Biology, and Medicine

iScience, Journal Year: 2020, Volume and Issue: 23(12), P. 101792 - 101792

Published: Nov. 10, 2020

The designed "ATCUN" motif (amino-terminal copper and nickel binding site) is a replica of naturally occurring ATCUN site found in many proteins/peptides, an attractive platform for multiple applications, which include nucleases, proteases, spectroscopic probes, imaging, small molecule activation. motifs are engineered at periphery by conjugation to recombinant proteins, peptides, fluorophores, or recognition domains through chemically genetically, fulfilling the needs various biological relevance wide range practical usages. This chemistry has witnessed significant growth over last few decades several interesting derivatives have been described. redox role moieties also important aspect be considered. potential M-ATCUN modulated judicious choice amino acid (including stereochemistry, charge, position) that ultimately leads catalytic efficiency. In this context, purposefully redox- non-redox-based including target-based metallodrugs, inhibition amyloid-β toxicity, telomere shortening, enzyme inactivation, biomolecules stitching modification, next-generation antibiotic,

Language: Английский

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Key Intermediate Species Reveal the Copper(II)‐Exchange Pathway in Biorelevant ATCUN/NTS Complexes

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(28), P. 11234 - 11239

Published: April 8, 2020

Abstract The amino‐terminal copper and nickel/N‐terminal site (ATCUN/NTS) present in proteins bioactive peptides exhibits high affinity towards Cu II ions have been implicated human physiology. Little is known, however, about the rate exact mechanism of formation such complexes. We used stopped‐flow microsecond freeze‐hyperquenching (MHQ) techniques supported by steady‐state spectroscopic electrochemical data to demonstrate partially coordinated intermediate complexes formed glycyl–glycyl–histidine (GGH) peptide, simplest ATCUN/NTS model. One these novel intermediates, characterized two‐nitrogen coordination, t 1/2 ≈100 ms at pH 6.0 ability maintain /Cu I redox pair best candidate for long‐sought reactive species extracellular transport.

Language: Английский

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Copper(II) import and reduction are dependent on His-Met clusters in the extracellular amino terminus of human copper transporter-1

Journal of Biological Chemistry, Journal Year: 2022, Volume and Issue: 298(3), P. 101631 - 101631

Published: Jan. 26, 2022

Copper(I) is an essential metal for all life forms. Though Cu(II) the most abundant and stable state, its reduction to Cu(I) via unclear mechanism prerequisite bioutilization. In eukaryotes, copper transporter-1 (CTR1) primary high-affinity importer, although role in remain uncharacterized. Here we show that extracellular amino-terminus of human CTR1 contains two methionine-histidine clusters neighboring aspartates distinctly bind preceding import. We determined hCTR1 localizes at basolateral membrane polarized MDCK-II cells endocytosis Common-Recycling-Endosomes regulated by subsequent coordination methionine cluster. demonstrate transient binding both during process facilitated also act as another crucial determinant endocytosis. Mutating first Methionine cluster (7Met-Gly-Met9) Asp13 abrogated uptake upon treatment. This phenotype could be reverted treating with reduced nonreoxidizable Cu(I). histidine clusters, on other hand, are functioning limiting copper. Finally, N-terminal His-Met-Asp exhibit functional complementarity, second sufficient preserve copper-induced complete deletion propose a novel detailed which residues not only copper, but maintain intracellular uptake.

Language: Английский

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Nuclease-like metalloscissors: Biomimetic candidates for cancer and bacterial and viral infections therapy

Coordination Chemistry Reviews, Journal Year: 2022, Volume and Issue: 458, P. 214417 - 214417

Published: Feb. 5, 2022

Language: Английский

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Oxidase-mimicking peptide-copper complexes and their applications in sandwich affinity biosensors

Analytica Chimica Acta, Journal Year: 2022, Volume and Issue: 1214, P. 339965 - 339965

Published: May 21, 2022

Language: Английский

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Overview on peptide-based electrochemical biosensors

International Journal of Electrochemical Science, Journal Year: 2023, Volume and Issue: 18(12), P. 100395 - 100395

Published: Nov. 1, 2023

Peptides have attracted great interest in the construction of electrochemical biosensors fields biomedicine, disease diagnosis, and environmental monitoring. They exhibit advantages high affinity specificity, chemical diversity building block amino acids, standard synthesis scheme. Versatile peptide-based been developed for detection various targets, including metal ions, enzymes, proteins, exosomes, cells, bacteria. their self-assembled nanostructures can be used as recognition elements, enzyme substrates, electrode materials, signal labels. Different functional species, electroactive small molecules, nanomaterials coupled with peptides direct conversion binding/modification events into measurable signals. Herein, we systematically summarize progress according to difference peptide function target type. The peptide-functionalized molecules amplification strategies improving sensitivity were discussed.

Language: Английский

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Copper‐Induced Supramolecular Peptide Assemblies for Multi‐pathway Cell Death and Tumor Inhibition

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(34)

Published: June 5, 2024

Although self-assembly has emerged as an effective tool for fabricating biomaterials, achieving precise control over the morphologies and functionalities of resultant assemblies remains ongoing challenge. Inspired by copper peptide naturally present in human plasma, this study, we designed a synthetic precursor, FcGH. FcGH can self-assemble via two distinct pathways: spontaneous Cu

Language: Английский

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Cu^II Binding Properties of N-Truncated Aβ Peptides: In Search of Biological Function

Inorganic Chemistry, Journal Year: 2019, Volume and Issue: 58(20), P. 13561 - 13577

Published: July 15, 2019

As life expectancy increases, the number of people affected by progressive and irreversible dementia, Alzheimer's Disease (AD), is predicted to grow. No drug designs seem be working in humans, apparently because origins AD have not been identified. Invoking amyloid cascade, metal ions, ROS production hypothesis AD, herein we share our point view on Cu(II) binding properties Aβ4–x, most prevalent N-truncated Aβ peptide, currently known as main constituent plaques. The capability Aβ4–x rapidly take over copper from previously tested Aβ1–x peptides form highly stable complexes, redox unreactive resistant exchange reactions, prompted us propose physiological roles for these peptides. We discuss new findings reactivity Cu(II)Aβ4–x with coexisting biomolecules context synaptic cleft; suggest that role quench toxicity brain maintain neurotransmission.

Language: Английский

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Metal–Peptide Complexes as Promising Antibiotics to Fight Emerging Drug Resistance: New Perspectives in Tuberculosis

Antibiotics, Journal Year: 2020, Volume and Issue: 9(6), P. 337 - 337

Published: June 18, 2020

In metal-peptide interactions, cations form stable complexes through bonds with coordinating groups as side chains of amino acids. These compounds, among other things, exert a wide variety antimicrobial activities structural changes peptides upon metal binding and redox chemistry. They exhibit different mechanisms action (MOA), including the modification DNA/RNA, protein cell wall synthesis, permeabilization modulation gradients cellular membranes. Nowadays, large increase in antibiotic resistance represents crucial problem to limit progression at pandemic level diseases that seemed nearly eradicated, such tuberculosis (Tb). Mycobacterium (Mtb) is intrinsically resistant many antibiotics due chromosomal mutations which can lead onset novel strains. Consequently, maximum pharmaceutical effort should be focused on development new therapeutic agents represent valuable option copious source potential bioactive compounds. The introduction center improve chemical diversity hence specificity bioavailability while, turn, coordination protect them enhance their poor water solubility air stability: optimization these parameters strictly required for drug prioritization obtain potent inhibitors Mtb infections MOAs. Here, we present panoramic review most recent findings field complex-peptide conjugates delivery systems application infections.

Language: Английский

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How trimerization of CTR1 N-terminal model peptides tunes Cu-binding and redox-chemistry

Chemical Communications, Journal Year: 2020, Volume and Issue: 56(81), P. 12194 - 12197

Published: Jan. 1, 2020

Trimeric arrangement of model peptides the CTR1 N-terminus promotes Cu(ii) reduction and Cu(i) binding.

Language: Английский

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