Oxygen-dependent cleavage of DNA by the 1,10-phenanthroline . cuprous complex. Inhibition of Escherichia coli DNA polymerase I.

Sigman, David S.; Graham, Daniel R.; D'Aurora, Vito; Stern, Andrew M.

doi:10.1016/s0021-9258(19)86305-6

Cited by 500 publications

(127 citation statements)

References 31 publications

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“…During the last decades, numerous studies comprising several FQs and different transition metals have been performed [ 30 , 31 , 33 , 34 , 35 , 51 , 52 , 53 , 54 , 55 , 56 ], including the solution study of binary and ternary complexes. Ternary complexes containing 1,10-phenanthroline (1,10-phen), a nitrogen donor heterocyclic ligand, were extensively explored due to the nuclease activity of this ligand when complexed to copper [ 57 , 58 , 59 ]. These findings triggered interest in the investigation of copper/phen complexes [ 60 , 61 ] and other complexes containing transition metal ions and phen.…”

Section: Fluoroquinolone Metalloantibioticsmentioning

confidence: 99%

Fluoroquinolone-Transition Metal Complexes: A Strategy to Overcome Bacterial Resistance

Ferreira

Gameiro

2021

Microorganisms

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Fluoroquinolones (FQs) are antibiotics widely used in the clinical practice due to their large spectrum of action against Gram‑negative and some Gram-positive bacteria. Nevertheless, the misuse and overuse of these antibiotics has triggered the development of bacterial resistance mechanisms. One of the strategies to circumvent this problem is the complexation of FQs with transition metal ions, known as metalloantibiotics, which can promote different activity and enhanced pharmacological behaviour. Here, we discuss the stability of FQ metalloantibiotics and their possible translocation pathways. The main goal of the present review is to frame the present knowledge on the conjunction of biophysical and biological tools that can help to unravel the antibacterial action of FQ metalloantibiotics. An additional goal is to shed light on the studies that must be accomplished to ensure stability and viability of such metalloantibiotics. Potentiometric, spectroscopic, microscopic, microbiological, and computational techniques are surveyed. Stability and partition constants, interaction with membrane porins and elucidation of their role in the influx, determination of the antimicrobial activity against multidrug‑resistant (MDR) clinical isolates, elucidation of the mechanism of action, and toxicity assays are described for FQ metalloantibiotics.

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Section: Fluoroquinolone Metalloantibioticsmentioning

confidence: 99%

Fluoroquinolone-Transition Metal Complexes: A Strategy to Overcome Bacterial Resistance

Ferreira

Gameiro

2021

Microorganisms

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“…[Cu(1,10‐phenantroline) 2 ] 2+ (CuPhen, Figure 7B) is the most widely studied AMN for both its cleavage mechanism and biological potential [121–124] . In the presence of exogenous reductant and oxidant, CuPhen induces direct single or double strand cleavage – arising from proximate single strand breaks – at the minor groove of poly[d(A−T) 2 ] sequences [125] . In the reduced form, CuPhen semi‐intercalates DNA promoting ROS, which causes abstraction primarily of the C1′ hydrogen atom (C5′ and C4′ to a lower extent) from the deoxyribose ring [126,127] .…”

Section: Artificial Metallonucleasesmentioning

confidence: 99%

DNA‐Targeted Metallodrugs: An Untapped Source of Artificial Gene Editing Technology

2021

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DNA binding metal complexes are synonymous with anticancer drug discovery. Given the array of structural and chemical reactivity properties available through careful design, metal complexes have been directed to bind nucleic acid structures through covalent or noncovalent binding modes. Several recognition modes – including crosslinking, intercalation, and oxidation – are central to the clinical success of broad‐spectrum anticancer metallodrugs. However, recent progress in nucleic acid click chemistry coupled with advancement in our understanding of metal complex–nucleic acid interactions has opened up new avenues in genetic engineering and targeted therapies. Several of these applications are enabled by the hybridisation of oligonucleotide or polyamine probes to discrete metal complexes, which facilitate site‐specific reactivity at the nucleic acid interface under the guidance of the probe. This Review focuses on recent advancements in hybrid design and, by way of an introduction to this topic, we provide a detailed overview of nucleic acid structures and metal complex–nucleic acid interactions. Our aim is to provide readers with an insight on the rational design of metal complexes with DNA recognition properties and an understanding of how the sequence‐specific targeting of these interactions can be achieved for gene engineering applications.

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“…Oxidative chemical nucleases, on the other hand, such as the copper(II) 1,10-phenanthroline (OP) complex Cu(OP) 2 (Scheme 1,C) induce direct strand scission on duplex DNA in the presence of exogenous reductant and oxidant. 4 Our group actively explore the biochemical and therapeutic applications of Cu(OP) 2 -based systems and have recently applied this oxidative nuclease to genetically engineer a library of high-affinity prostate-specific antigen (PSA) binding antibodies through a process called DNA shuffling. 5 In this work, the selectivity and diversity of the Cu(OP) 2 recombinant antibody library was then compared directly to a library of mutant PSA-specific antibodies generated by DNase I.…”

Section: Syn Lettmentioning

confidence: 99%

“…The artificial nuclease activity of Cu(OP) 2 was discovered by Sigman in 1979 when the complex was observed to shear duplex DNA along A-T rich chains in the minor groove 4 with abstraction of C1′-hydrogen predominating over C5′ and C4′ positions. 6 Indeed, scission takes place preferentially in the minor groove on account of the binding interaction by the tetrahedral complex geometry assumed by Cu(OP) 2 in its cuprous form.…”

Section: Syn Lettmentioning

confidence: 99%

Genome Engineering with Synthetic Copper Nucleases

Fantoni

Lauria

Kellett

2015

Synlett

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Oxidative chemical nucleases represent an important class of synthetic compound that mediate nucleic acid recognition and strand scission. These agents have found utility as footprinting probes to map drug-DNA and protein-DNA interactions and also as clinical cytotoxins of human cancer. Herein, we highlight a recent contribution from our group on the application of the copper(II) 1,10-phenanthroline (OP) complex Cu(OP) 2 as a novel DNA-shuffling agent capable of generating highly diverse mutant protein antibody libraries. By employing a recombinant antibody gene fragment specific for prostate-specific antigen (PSA), we compared variation and PSA-binding specificity within Taq DNA polymerase I reconstructed Cu(OP) 2 oxidative digest fragments with hydrolytic restriction digests generated by DNase I. Results show the Cu(OP) 2 mutant library contained highly PSA-specific binding antibodies thus indicating that oxidative chemical nucleases may be applied to generate novel antibody clones not accessible through the use of the traditional DNA-shuffling enzyme DNase I. Key words copper(II), nuclease, nucleic acids, radical oxidation, H-atom abstraction, strand scissionIn the field of DNA manipulation, the design of artificial DNA cutters has become an area of considerable research interest. Synthetic copper chemical nucleases are a class of DNA cutter and can be categorised in two ways: i) those that mimic natural restriction endonucleases by catalysing hydrolysis of the phosphodiester backbone, 1 and ii) compounds that induce direct strand scission by oxidative Hatom abstraction from the pentose ring of DNA. 2 The biochemistry of bovine pancreatic deoxyribonuclease (DNase I) -a calcium-and magnesium-dependent hydrolytic enzyme that nonspecifically degrades both single-and double-stranded DNA -is described in Scheme 1 (A). Here, glutamate (Glu75) and histidine (His131) residues combine to catalyse hydroxide anion formation in proximity to the phosphate backbone. 3 The resulting 5′-phosphorylated and 3′-hydroxylated ends produced by hydrolytic nucleases (e.g., DNase I or site-specific restriction endonucleases) can then be further manipulated, for example, in DNA recombi-

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Oxygen-dependent cleavage of DNA by the 1,10-phenanthroline . cuprous complex. Inhibition of Escherichia coli DNA polymerase I.

Cited by 500 publications

References 31 publications

Fluoroquinolone-Transition Metal Complexes: A Strategy to Overcome Bacterial Resistance

Fluoroquinolone-Transition Metal Complexes: A Strategy to Overcome Bacterial Resistance

DNA‐Targeted Metallodrugs: An Untapped Source of Artificial Gene Editing Technology

Genome Engineering with Synthetic Copper Nucleases

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