Toward the development of metal-based synthetic nucleases and peptidases: a rationale and progress report in applying the principles of coordination chemistry

Hegg, Eric L.; Burstyn, Judith N.

doi:10.1016/s0010-8545(98)00157-x

Cited by 583 publications

(455 citation statements)

References 141 publications

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“…The cleavage reactions were observed even in the presence of dinitrogen ruling out the possibility of an oxidative cleavage pathway. The commonly accepted mechanism of hydrolysis of deoxynucleotide phosphates involves a nucleophilic attack of a water oxygen to the phosphorus to give a five co-ordinate phosphate intermediate [21,74]. In the present complexes, the higher rate of hydrolysis observed for the complex 1 may be traced to the presence of axially coordinated water molecule, which may be activated as a nucleophile for the hydrolytic cleavage [75,76].…”

Section: Hydrolytic Cleavage Of Dnamentioning

confidence: 73%

“…A number of metal complexes have been shown to hydrolyze phosphate ester [19] as well as RNA with varying efficiencies [20]; however, they are unable to hydrolyze the phosphate diester backbone of DNA. Burstyn and co-worker reported that copper(II)-macrocyclic triamine complexes promote the hydrolytic cleavage of plasmid DNA [21]. In recent years, there has been substantial interest in the design and study of Lewis acidic, potential redox and spectroscopically active Cu(II/I) complexes of synthetic and naturally occurring ligands as nuclease mimics [22][23][24][25] and in fact, a few copper(II) complexes have been shown to be capable of mediating non-random double-strand cleavage of plasmid DNA.…”

Section: Introductionmentioning

confidence: 99%

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Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

Selvakumar

Rajendiran

Maheswari

et al. 2006

Journal of Inorganic Biochemistry

290

140

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Section: Hydrolytic Cleavage Of Dnamentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

Selvakumar

Rajendiran

Maheswari

et al. 2006

Journal of Inorganic Biochemistry

290

140

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“…S9 and S10). Whether the mode of zinc-mediated ester hydrolysis proceeds by internal or external hydroxide attack remains to be determined (42). Of note, DA-ZP1-TPP retained a measure of reversibility, differentiating it from most reaction-based probes (30).…”

Section: Zp1-tpp Is Sequestered In Endosomes/lysosomes and Unable Tomentioning

confidence: 99%

Reaction-based fluorescent sensor for investigating mobile Zn ²⁺ in mitochondria of healthy versus cancerous prostate cells

Chyan

Zhang

Lippard

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

150

121

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Chelatable, mobile forms of divalent zinc, Zn(II), play essential signaling roles in mammalian biology. A complex network of zinc import and transport proteins has evolved to control zinc concentration and distribution on a subcellular level. Understanding the action of mobile zinc requires tools that can detect changes in Zn(II) concentrations at discrete cellular locales. We present here a zinc-responsive, reaction-based, targetable probe based on the diacetyled form of Zinpyr-1. The compound, (6-amidoethyl)triphenylphosphonium Zinpyr-1 diacetate (DA-ZP1-TPP), is essentially nonfluorescent in the metal-free state; however, exposure to Zn (II) triggers metal-mediated hydrolysis of the acetyl groups to afford a large, rapid, and zinc-induced fluorescence response. DA-ZP1-TPP is insensitive to intracellular esterases over a 2-h period and is impervious to proton-induced turn-on. A TPP unit is appended for targeting mitochondria, as demonstrated by live cell fluorescence imaging studies. The practical utility of DA-ZP1-TPP is demonstrated by experiments revealing that, in contrast to healthy epithelial prostate cells, tumorigenic cells are unable to accumulate mobile zinc within their mitochondria.reaction-based probe | prostate cancer | zinc biology | fluorescence microscopy

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“…12 In the latter case, the metal ion also induces a proximity effect by bringing both reactants into the inner coordination sphere while proceeding through a five-coordinate intermediate. If other factors are held constant, the mechanism shown in Scheme 2b should lead to higher enzymatic activity.…”

Section: Introductionmentioning

confidence: 99%

Geometric Preferences in Iron(II) and Zinc(II) Model Complexes of Peptide Deformylase

et al. 2006

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A combination of experimental and theoretical studies on (N,S(thiolate))M II -formate complexes (M = Fe, Zn) suggests a rationale for the metal ion dependence of peptide deformylase.Based on active site structure (tetrahedral (His 2 Cys)M II (OH n )), conserved sequence motifs, and function (hydrolysis), peptide deformylase (PDF) belongs to the mononuclear zinc(II) enzyme family. 1 However, recent evidence shows bacterial PDF to be the first example of an iron(II) metallopeptidase, which hydrolyzes the formyl bond of the N-terminus of newly synthesized polypeptides. [2][3][4] Intriguingly, the Zn II form of bacterial PDF is dramatically less active than the Fe II form, although their native structures are identical. [4][5][6] The mechanism of this enzyme and an explanation of the metal-ion dependence are under investigation. PDF is also a target for new antibiotic agents, and therefore knowledge regarding its mechanism is of practical significance. 7 We are involved in the synthesis of Zn II and Fe II model complexes of PDF to gain a better understanding of the mechanism and unusual metal dependence of this enzyme.Previously we reported the synthesis of (PATH)Zn II (O 2 CH), a model complex of the putative (formate)Zn II -PDF intermediate. 8 Analysis of the bonding mode in this complex showed that the formate was coordinated in an anisobidentate fashion. It was suggested that this bonding mode, as opposed to a purely monodentate interaction, might slow down the displacement of formate by water in the final step of the catalytic cycle, and account for the low reactivity of Zn-PDF. Following this argument, it was expected that the analogous (formate)Fe II -PDF would exhibit a monodentate bonding mode.Recently, high-resolution X-ray structures of (formate)M II -PDF (M = Zn, Fe) from Chan and coworkers have revealed bonding motifs in contrast to our prediction; monodentate coordination was observed in the case of Zn II and bidentate coordination was seen for Fe II The synthesis of 1 is shown in Scheme 1. Addition of (Py 2 S − )Na + to ferrous formate in MeOH gives a cloudy, yellow solution which turns clear over 18 h. Removal of the solvent under vacuum gives an orange solid which can be partly redissolved in toluene. Crystals of 1 were grown from Et 2 O/toluene, and an ORTEP diagram of 1 is shown in Figure 1. The iron center is in a five-coordinate geometry with the formate ligand occupying the axial position opposite the N(amine) donor. The N(pyridyl)-Fe II and S-Fe II distances (Table 1) are in the normal range. The N(amine)-Fe II distance of 2.366(4) Å is long, but is quite close to the related complexes (Py 2 S)Fe II X (X = Br, N(amine)-Fe II = 2.387(1) Å; X = Cl (2.352(2) Å). 10 There is no obvious reason for the elongation of this bond in these complexes, and theoretical calculations show that another isomer of 1 with a more conventional Fe II -N(amine) distance should be accessible (vide infra). Interestingly, the formate ligand is clearly monodentate with Fe-O(2) = 4.12 Å, and is in fact bound in ...

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Toward the development of metal-based synthetic nucleases and peptidases: a rationale and progress report in applying the principles of coordination chemistry

Cited by 583 publications

References 141 publications

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

Reaction-based fluorescent sensor for investigating mobile Zn ²⁺ in mitochondria of healthy versus cancerous prostate cells

Geometric Preferences in Iron(II) and Zinc(II) Model Complexes of Peptide Deformylase

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Toward the development of metal-based synthetic nucleases and peptidases: a rationale and progress report in applying the principles of coordination chemistry

Cited by 583 publications

References 141 publications

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

Reaction-based fluorescent sensor for investigating mobile Zn 2+ in mitochondria of healthy versus cancerous prostate cells

Geometric Preferences in Iron(II) and Zinc(II) Model Complexes of Peptide Deformylase

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Reaction-based fluorescent sensor for investigating mobile Zn ²⁺ in mitochondria of healthy versus cancerous prostate cells