Double strand DNA cleavage with a binuclear iron complex

Berg, Tieme A. van den; Feringa, Ben L.; Roelfes, Gérard

doi:10.1039/b613469f

Cited by 55 publications

(47 citation statements)

References 26 publications

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“…Such a sudden increase in ds cleavage activity has been observed previously, whereupon it was demonstrated that the dinuclear iron complexes were more efficient in bringing about double-strand cleavage of nicked DNA than that of supercoiled DNA. [28] In view of their structural similarity to the present complexes, this is most likely the case here as well.…”

Section: Resultsmentioning

confidence: 85%

“…A correction factor of 1.31 was used to compensate for the reduced ethidium bromide uptake capacity of supercoiled DNA. [28] Figure 5. Number of double-strand cuts per DNA molecule (m) as a function of the number of single-strand cuts per DNA molecule (n) for 29 (!…”

Section: Resultsmentioning

confidence: 98%

“…[6,40] The same reactivity pattern has been observed previously with other N4Py-based dinuclear complexes having different linking moieties. [28] In the case of complexes 30-32, approximately equal amounts of linear DNA were produced, [39] indicating that these complexes show comparable activities towards doublestrand DNA cleavage.…”

Section: Resultsmentioning

confidence: 99%

“…[28] For the synthesis of the tritopic ligand 8 with a flexible core, a slightly modified approach was used (Scheme 2). The core moiety was prepared starting from 4-ketopimelic acid.…”

Section: Resultsmentioning

confidence: 99%

“…[27] Recently, we reported on a binuclear iron complex, based on N4Py, that showed significantly enhanced double-strand cleavage activity. [28] Multinuclear copper complexes have also been investigated in relation to DNA cleavage. [29][30][31][32][33][34][35][36][37] It has been reported that dinuclear copper complexes show increased activity compared to their mononuclear counterparts.…”

Section: Introductionmentioning

confidence: 99%

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Multinuclear Non‐Heme Iron Complexes for Double‐Strand DNA Cleavage

Megens

Berg

Bruijn

et al. 2009

Chemistry A European J

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The cytotoxicity of the anti-tumor drug BLM is believed to be related to the ability of the corresponding iron complex (Fe-BLM) to engage in oxidative double-strand DNA cleavage. The iron complex of the ligand N4Py (Fe-N4Py; N4Py = N,N-bis(2-pyridyl)-N-bis(2-pyridyl)methylamine) has proven to be a particularly valuable spectroscopic and functional model for Fe-BLM. It is also a very active oxidative DNA-cleaving agent. However, like all other synthetic Fe-BLM mimics, it gives only single-strand DNA cleavage. Since double-strand DNA cleavage requires the delivery of two oxidizing equivalents to the DNA, it was envisaged that multinuclear iron complexes might be capable of effecting double-strand cleavage. For this purpose, a series of ditopic and tritopic N4Py-derived ligands has been synthesized and the corresponding iron complexes have been evaluated for their efficacy in the oxidative cleavage of supercoiled pUC18 plasmid DNA. The dinuclear iron complexes showed significantly enhanced double-strand cleavage activity compared to mononuclear Fe-N4Py, which was relatively independent of the structure of the linking moiety. Covalent attachment of a 9-aminoacridine intercalator to a dinuclear complex did not give rise to improved double-strand DNA cleavage. The most efficient oxidative double-strand cleavage agents proved to be the trinuclear iron complexes. This is presumably the result of increased probability of the simultaneous delivery of two oxidizing equivalents to the DNA.

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Section: Resultsmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

“…[28] For the synthesis of the tritopic ligand 8 with a flexible core, a slightly modified approach was used (Scheme 2). The core moiety was prepared starting from 4-ketopimelic acid.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Multinuclear Non‐Heme Iron Complexes for Double‐Strand DNA Cleavage

Megens

Berg

Bruijn

et al. 2009

Chemistry A European J

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A 1 : 2 Copper(II)–Tripeptide Complex for DNA Binding and Cleavage Agent under Physiological Conditions

Reddy

Pallerla

Chakraborty

et al. 2009

Chemistry & Biodiversity

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A 1 : 2 copper-tripeptide complex, [Cu(II)(Boc-His-Gly-His-OMe)(2)](2+), was synthesized and structurally characterized. The absorption band at 577 nm suggests a square-planar geometry around Cu(II). The DNA-binding and DNA-cleavage properties of the Cu(II) complex were investigated. The complex binds to calf thymus DNA (CT DNA) in an intercalative fashion and cleaves plasmid pUC-19 DNA hydrolytically at micromolar concentrations under physiological conditions. The intrinsic binding constant (K(b)=1.2x10(2) M(-1)) for the binding of Cu-tripeptide complex with DNA suggests that this complex is suitable for rapid diffusion on the pharmacological time scale.

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Iron(III) Complexes of Metal‐Binding Copolymers as Proficient Catalysts for Acid Hydrolysis of Phosphodiesters and Oxidative DNA Cleavage – Insight into the Rational Design of Functional Metallopolymers

et al. 2009

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Fe3+ complexes of pyridine-containing copolymers were found to be efficient and selective catalysts toward phosphodiester hydrolysis and show significant activity toward oxidative DNA cleavage. The catalysis toward bis(p-nitrophenyl)phosphate (BNPP) hydrolysis exhibits enzyme-like pre-equilibrium kinetics with maximum activities in the range of ca. pH 6-8 and a first-order catalytic proficiency (k cat /k o ) of 4.2ϫ 10 7 -fold at the acidic pH value of 5.3 (i.e., pK a of the coordinated nucleophilic water) and 25°C, entitling this Fe 3+ copolymer an acid phosphodiester catalyst.

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Double strand DNA cleavage with a binuclear iron complex

Abstract: Covalently linking two single strand DNA cleaving agents resulted in a new biomimetic binuclear iron complex capable of effecting oxidative double strand DNA cleavage.

Cited by 55 publications

References 26 publications

Multinuclear Non‐Heme Iron Complexes for Double‐Strand DNA Cleavage

Multinuclear Non‐Heme Iron Complexes for Double‐Strand DNA Cleavage

A 1 : 2 Copper(II)–Tripeptide Complex for DNA Binding and Cleavage Agent under Physiological Conditions

Iron(III) Complexes of Metal‐Binding Copolymers as Proficient Catalysts for Acid Hydrolysis of Phosphodiesters and Oxidative DNA Cleavage – Insight into the Rational Design of Functional Metallopolymers

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