Progress in artificial metallonucleases

Mancin, Fabrizio; Scrimin, Paolo; Tecilla, Paolo

doi:10.1039/c2cc30952a

Cited by 166 publications

(117 citation statements)

References 159 publications

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“…These observations are consistent with the reported hydrolytic ability of both metal ions in small-molecule biomimetic and sensing systems (42,(46)(47)(48). Co(II)-mediated ester hydrolysis was fit to a single exponential function with t 1/2-Co(II) = 3.04 s (SI Appendix, Fig.…”

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

confidence: 74%

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

confidence: 74%

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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“…4 Nevertheless, the sequence-specific hydrolytic cleavage of DNA and RNA is important not only in metabolic and regulatory processes but also in the fields of molecular biology, biochemistry and most importantly in the development of novel cancer therapies. 5 Over the last 20 years much interest has focused on the rational design of hydrolytic enzyme mimics [6][7][8][9][10][11] which can provide mechanistic insight into the chemical process of hydrolysis, be employed as artificial restriction enzymes for molecular biology and help realise the development of anti-DNA drugs in the near future. 12 Effective examples of hydrolytic enzyme mimics exist based on both transition metals (Zn (II), Fe(III), etc.)…”

Section: Introductionmentioning

confidence: 99%

Tri- and tetra-substituted cyclen based lanthanide(iii) ion complexes as ribonuclease mimics: a study into the effect of log K_a, hydration and hydrophobicity on phosphodiester hydrolysis of the RNA-model 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP)

2015

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A series of tetra-substituted 'pseudo' dipeptide ligands of cyclen (1,4,7,10,-tetraazacyclododecane) and a tri-substituted 3'-pyridine ligand of cyclen, and the corresponding lanthanide(III) complexes were synthesised and characterised as metallo-ribonuclease mimics. All complexes were shown to promote hydrolysis of the phosphodiester bond of 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP, τ 1/2 = 5.87 × 10 3 h), a well known RNA mimic. The La(III) and Eu(III) tri-substituted 3'-pyridine lanthanide(III) complexes being the most efficient in promoting such hydrolysis at pH 7.4 and at 37°C; with τ 1/2 = 1.67 h for La(III) and 1.74 h for Eu(III). The series was developed to provide the opportunity to investigate the consequences of altering the lanthanide(III) ion, coordination ability and hydrophobicity of a metallo-cavity on the rate of hydrolysis using the model phosphodiester, HPNP, at 37°C. To further provide information on the role that the log K a of the metal bound water plays in phosphodiester hydrolysis the protonation constants and the metal ion stability constants of both a tri and tetra-substituted 3'pyridine complex were determined.Our results highlighted several key features for the design of lanthanide(III) ribonucelase mimics; the presence of two metal bound water molecules are vital for pH dependent rate constants for Eu(III) complexes, optimal pH activity approximating physiological pH (∼7.4) may be achieved if the log K a values for both MLOH and ML(OH) 2 species occur in this region, small changes to hydrophobicity within the metallo cavity influence the rate of hydrolysis greatly and an amide adjacent to the metal ion capable of forming hydrogen bonds with the substrate is required for achieving fast hydrolysis.

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“…[12] The numerous analogous multivalent systems (both molecular and NP-based) that have been reported require the presence of Zn 2+ or other metal ions (for example, Cu 2+ , Co 3+ , Ce 4+ , Fe 3+ ) for catalytic activity. [18] The observation that Au NP 1 and related systems are poorly active in the absence of metal ions implies that the controlled association and dissociation of metal ions can be used as a regulatory mechanism for catalysis. The low residual activity of non-metalated Au NP 1 presumably originates from the presence of protonated TACN-ligands, at neutral or acidic pH.…”

mentioning

confidence: 99%

“…It is pointed out that the absolute activities of the Cu 2+ and Cd 2+ systems are much lower compared to that of the analogous Zn 2+ system that we have studied previously. [12,17,18] Yet, the more accessible redox-chemistry of Cu and Cd made us focus on these metals, despite the lower catalytic activity. Second, the difference in terms of binding affinity for the TACN group is about six orders of magnitude in favor of Cu 2+ (log K TACNÁCu 2þ = 15.4 and log K TACNÁCd 2þ = 9.3), [20] resulting in complete displacement of Cd 2+ ions from the NP-bound TACN head groups upon the addition of just an equimolar amount of Cu 2+ ions.…”

mentioning

confidence: 99%

Reversible Electrochemical Modulation of a Catalytic Nanosystem

et al. 2016

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A catalytic system based on monolayer-functionalized gold nanoparticles (Au NPs) that can be electrochemically modulated and reversibly activated is reported. The catalytic activity relies on the presence of metal ions (Cd 2+ and Cu 2+ ), which can be complexed by the nanoparticle-bound monolayer. This activates the system towards the catalytic cleavage of 2-hydroxypropyl-p-nitrophenyl phosphate (HPNPP), which can be monitored by UV/Vis spectroscopy. It is shown that Cu 2+ metal ions can be delivered to the system by applying an oxidative potential to an electrode on which Cu 0 was deposited. By exploiting the different affinity of Cd 2+ and Cu 2+ ions for the monolayer, it was also possible to upregulate the catalytic activity after releasing Cu 2+ from an electrode into a solution containing Cd 2+ . Finally, it is shown that the activity of this supramolecular nanosystem can be reversibly switched on or off by oxidizing/reducing Cu/Cu 2+ ions under controlled conditions. Complexityisemergingasamajorthemeinchemistry. [1] Notonly does it mark a shift from the study of relatively simple molecules to complex molecular structures similar to those found in nature, but it also marks a shift from the study of single molecules to networks of molecules. [2][3][4] Within the subfield of catalysis, [5] the emergence of nanozymes, defined as nanomaterials with enzyme-like activity, nicely illustrates this development. [6] Nanozymes are prepared following a bottom-up strategy relying on the use of simple synthetic components for the formation of structures with a size and structural complexity similar to that of enzymes. [7,8] Their high stability, uniformity, and ease of modification is favoring applications in the fields of sensing, [9] materials science, [10] and systems chemistry. [11] The observation that nanozymes can exhibit an emerging property such as cooperativity is indeed a sign that significant progress has been made in the design of functional complex systems. [12] However, whereas nature has gained exquisite control over the complex biological machinery by using specific triggers to up-and down-regulate catalytic processes, similar regulatory pathways are still largely inexistent for nanozymes. Herein, we present a simple setup for the reversible activation and modulation of nanozymes using an electronic input. The electrochemical activation is highly attractive because of its ease of implementation, cleanliness, precision, and rapid response. [13][14][15][16] The availability of this kind of regulatory mechanism will strongly determine the success of chemists in constructing synthetic networks for studying complexity on the systems level.The main component of our system is Au NP 1, which are gold nanoparticles (d = 1.5 AE 0.3 nm) covered with C9-thiols terminating with a 1,4,7-triazacyclononane (TACN) head group (Figure 1 a). [11] Such nanoparticle-bound TACN moieties are able to coordinate Zn 2+ -metal ions forming a supra-

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Progress in artificial metallonucleases

Cited by 166 publications

References 159 publications

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

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

Tri- and tetra-substituted cyclen based lanthanide(iii) ion complexes as ribonuclease mimics: a study into the effect of log K_a, hydration and hydrophobicity on phosphodiester hydrolysis of the RNA-model 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP)

Reversible Electrochemical Modulation of a Catalytic Nanosystem

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Progress in artificial metallonucleases

Cited by 166 publications

References 159 publications

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

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

Tri- and tetra-substituted cyclen based lanthanide(iii) ion complexes as ribonuclease mimics: a study into the effect of log Ka, hydration and hydrophobicity on phosphodiester hydrolysis of the RNA-model 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP)

Reversible Electrochemical Modulation of a Catalytic Nanosystem

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

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

Tri- and tetra-substituted cyclen based lanthanide(iii) ion complexes as ribonuclease mimics: a study into the effect of log K_a, hydration and hydrophobicity on phosphodiester hydrolysis of the RNA-model 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP)