Fluorophore ATCUN complexes: combining agent and probe for oxidative DNA cleavage

Wende, Christian; Kulak, Nora

doi:10.1039/c5cc04508h

Cited by 27 publications

(19 citation statements)

References 35 publications

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“…Cu 2+ and Ni 2+ can bind to the motif with a high affinity [ 118 ]. The Cu 2+ -ATCUN complex can produce reactive oxygen species (ROS) [ 119 , 120 ], which target nucleic acids, proteins and lipids [ 118 ].…”

Section: Structure and Characteristics Of Ampsmentioning

confidence: 99%

Antimicrobial peptides: mechanism of action, activity and clinical potential

et al. 2021

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The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria. As an excellent candidate to overcome antibiotic resistance, antimicrobial peptides (AMPs) that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity. These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action. This comprehensive review provides a broad overview of AMPs from the origin, structural characteristics, mechanisms of action, biological activities to clinical applications. We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.

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Section: Structure and Characteristics Of Ampsmentioning

confidence: 99%

Antimicrobial peptides: mechanism of action, activity and clinical potential

et al. 2021

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“…Utilizing the backbone of Imperiali and co‐workers, the Kulak group took the compound R‐NH 2 ‐Dap‐β‐Ala‐His‐Ser‐Ser‐CONH 2 and attached different fluorophores (R=fluorophore=Rhodamine B, dansyl chloride, fluorescein isothiocyanate) to it⋅ They were able to show that their analogs cleaved DNA efficiently with a minimal concentration of 25 μ m , but only in the presence of a reducing agent like ascorbic acid. The attached fluorophore allowed them to monitor the reduction of Cu II to Cu I , through the fluorescence turn‐on, as Cu I is diamagnetic and hence does not quench the fluorophore like Cu II does.…”

Section: Applicationsmentioning

confidence: 99%

N‐Terminal Cu‐Binding Motifs (Xxx‐Zzz‐His, Xxx‐His) and Their Derivatives: Chemistry, Biology and Medicinal Applications

González

Bossak

Stefaniak

et al. 2018

Chemistry A European J

110

203

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Peptides and proteins with N-terminal amino acid sequences NH -Xxx-His (XH) and NH -Xxx-Zzz-His (XZH) form well-established high-affinity Cu -complexes. Key examples are Asp-Ala-His (in serum albumin) and Gly-His-Lys, the wound healing factor. This opens a straightforward way to add a high-affinity Cu -binding site to almost any peptide or protein, by chemical or recombinant approaches. Thus, these motifs, NH -Xxx-Zzz-His in particular, have been used to equip peptides and proteins with a multitude of functions based on the redox activity of Cu, including nuclease, protease, glycosidase, or oxygen activation properties, useful in anticancer or antimicrobial drugs. More recent research suggests novel biological functions, mainly based on the redox inertness of Cu in XZH, like PET imaging (with Cu), chelation therapies (for instance in Alzheimer's disease and other types of neurodegeneration), antioxidant units, Cu transporters and activation of biological functions by strong Cu binding. This Review gives an overview of the chemical properties of Cu-XH and -XZH motifs and discusses the pros and cons of the vastly different biological applications, and how they could be improved depending on the application.

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“…The above designed ATCUN derivatives are also conjugated with small organic molecules at positions 1, 2, 3 and NH 2 - (in N-terminus site) with or without a linker moiety. This designed has been, particularly, developed as a sensor ( Yu and Cowan, 2017a , 2017b ; Gonzalez et al., 2018 ; Torrado et al., 1998 ; Wendea and Kulak, 2015 ; Libardo et al., 2014 ). Torrado et al.…”

Section: Design Of Atcun Derivativesmentioning

confidence: 99%

“…redesigned a series of ATCUN conjugated fluorophore (R-NH 2 -Dap-β-Ala-His-Ser-Ser-CONH 2 ; R = fluorophore = Rhodamine B, dansyl chloride and fluorescein isothiocyanate) derivatives that significantly cleaved DNA through oxidative pathway. The fate of metal ion (Cu II ), during the redox process, was monitored by fluorescence studies ( Wendea and Kulak, 2015 ).…”

Section: Applications Of M-atcun Derivativesmentioning

confidence: 99%

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

et al. 2020

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

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Fluorophore ATCUN complexes: combining agent and probe for oxidative DNA cleavage

Abstract: DNA can be oxidatively cleaved by copper complexes of the ATCUN peptide (amino terminal Cu(II)- and Ni(II)-binding motif). In order to investigate the fate of the metal ion throughout this process, we have exploited quenching/dequenching effects of conjugated fluorophores.

Cited by 27 publications

References 35 publications

Antimicrobial peptides: mechanism of action, activity and clinical potential

Antimicrobial peptides: mechanism of action, activity and clinical potential

N‐Terminal Cu‐Binding Motifs (Xxx‐Zzz‐His, Xxx‐His) and Their Derivatives: Chemistry, Biology and Medicinal Applications

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

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