Detection of Enzymatic Activity by PARACEST MRI: A General Approach to Target a Large Variety of Enzymes

Chauvin, Thomas; Durand, Philippe; Bernier, Michèle; Meudal, Hervé; Doan, Bich‐Thuy; Noury, Fanny; Badet, Bernard; Belœil, Jean‐Claude; Tóth, Éva

doi:10.1002/anie.200800809

Cited by 138 publications

(109 citation statements)

References 24 publications

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“…[8,12,24] In this initial work, the hydrolase activity that is targeted is that of β-galactosidase (1, Figure 3). This enzyme is the product of a prominent reporter gene system.…”

Section: Resultsmentioning

confidence: 99%

“…[2] A number of smart contrast agents have already been introduced, among them those that detect copper, zinc, or calcium ions [3][4][5][6] , as well as those that reveal a specific enzymatic activity. [7][8][9][10][11][12] They all have in common the presence of a gadolinium(III) atom at their center that is a permanently paramagnetic lanthanide ion. We have opted for iron(II) as this paramagnetic center in order to capitalize on its exceptional property of adopting a diamagnetic as well as a paramagnetic state depending on ligand-field strength.…”

Section: Introductionmentioning

confidence: 99%

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Effective Repression of the Fragmentation of a Hexadentate Ligand Bearing an Auto‐Immolable Pendant Arm by Iron Coordination

et al. 2008

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International audienceA diamagnetic ferrous complex (1) (MRI silent) is presented that consists of a macrocyclic hexadentate ligand (7) bearing an auto-immolable arm, as seen in organic prodrug design. This arm constitutes a phenylogous N/O acetal “locked” by glycosylation. Enzymatic glycolysis is hypothesized to lead to a phenol intermediate (a phenylogous hemiaminal) that fragments spontaneously thereby liberating a paramagnetic ferrous complex (MRI active). This paper describes the synthesis of ligand 7 and complex 1, and their respective reaction with β-galactosidase, the target enzyme. While ligand 7 alone fragments swiftly to the pentadentate ligand dptacn (monitored by LCMS analysis) upon in vitro enzymatic conversion, the phenol resulting from glycosyl removal from complex 1 accumulates in the buffered reaction mixture without any apparent fragmentation. Two independent explanations are put forward: metal coordination leads to rigidification of the ligand skeleton with concomitant kinetic inhibition of fragmentation or to the liberation of enough extra free energy to shift the thermodynamic equilibrium towards the starting material

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“…[8,12,24] In this initial work, the hydrolase activity that is targeted is that of β-galactosidase (1, Figure 3). This enzyme is the product of a prominent reporter gene system.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effective Repression of the Fragmentation of a Hexadentate Ligand Bearing an Auto‐Immolable Pendant Arm by Iron Coordination

et al. 2008

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“…The use of paraCEST was illustrated by Toth et al whereby action of bGal converted a masked carbamate to an View Article Online amine with concomitant changes in the paraCEST properties of a Yb(III)-chelating unit due to the different exchange rates and chemical shifts of the carbamate and amine protons. 146 This approach allowed the monitoring of the kinetics of enzyme catalysed bond cleavage.…”

Section: Probes Based On Lanthanide Relaxivitymentioning

confidence: 99%

Recent advances in the development of synthetic chemical probes for glycosidase enzymes

2015

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The emergence of synthetic glycoconjugates as chemical probes for the detection of glycosidase enzymes has resulted in the development of a range of useful chemical tools with applications in glycobiology, biotechnology, medical and industrial research. Critical to the function of these probes is the preparation of substrates containing a glycosidic linkage that when activated by a specific enzyme or group of enzymes, irreversibly releases a reporter molecule that can be detected. Starting from the earliest examples of colourimetric probes, increasingly sensitive and sophisticated substrates have been reported. In this review we present an overview of the recent advances in this field, covering an array of strategies including chromogenic and fluorogenic substrates, lanthanide complexes, gels and nanoparticles. The applications of these substrates for the detection of various glycosidases and the scope and limitations for each approach are discussed.

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“…[8] The field of “catalyCEST MRI” has been used to detect enzyme-mediated catalysis of caspase-3, [7] urokinase Plasminogen Activator, [8,9] cathepsin B, [10] cathepsin D, [11] transglutaminase, [12] β-galactosidase, [13] esterase, [14] protein kinase A, [15] and cytosine deaminase [16] enzymes. In some cases, we and others have developed diamagnetic catalyCEST agents that do not require a potentially toxic metal ion, which facilitates clinical translation.…”

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confidence: 99%

A CatalyCEST MRI Contrast Agent that Can Simultaneously Detect Two Enzyme Activities

2016

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The simultaneous detection of multiple enzyme activities can improve the specificity of disease diagnoses. We have synthesized and characterized a diamagnetic CEST MRI contrast agent that can simultaneously detect two enzyme activities. Sulfatase and esterase enzymes cleaved the ligands of the CEST agent, to release salicylic acid that was detected with CEST MRI. Importantly, both enzymes were required to activate the agent to produce a CEST MRI contrast, and the CEST agent was stable without enzyme treatment. These results have established that this diamagnetic CEST MRI contrast agent is a platform technology with a modular design that can be potentially exploited to detect other combinations of enzyme activities, which can expand the armamentarium of contrast agents for molecular imaging.

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Detection of Enzymatic Activity by PARACEST MRI: A General Approach to Target a Large Variety of Enzymes

Cited by 138 publications

References 24 publications

Effective Repression of the Fragmentation of a Hexadentate Ligand Bearing an Auto‐Immolable Pendant Arm by Iron Coordination

Effective Repression of the Fragmentation of a Hexadentate Ligand Bearing an Auto‐Immolable Pendant Arm by Iron Coordination

Recent advances in the development of synthetic chemical probes for glycosidase enzymes

A CatalyCEST MRI Contrast Agent that Can Simultaneously Detect Two Enzyme Activities

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