A Chemiluminescent Probe for HNO Quantification and Real‐Time Monitoring in Living Cells

An, Weiwei; Ryan, Lucas S.; Reeves, Audrey G.; Bruemmer, Kevin J.; Mouhaffel, Lyn; Gerberich, Jeni; Winters, Alexander; Mason, Ralph P.; Lippert, Alexander R.

doi:10.1002/anie.201811257

Cited by 95 publications

(76 citation statements)

References 58 publications

(66 reference statements)

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“…Additionally,m ice were used to monitor and trace the NTR catalytic kinetics with Zn-MPB'L-NO 2 .M ice fluorescent imaging [39,40] tests were performed at an excitation wavelength of 470 nm and emission was collected at 530 nm by using Bruker In Vivo FPro system. MCF-7 and MDA-MB-231 tumor-bearing mice were used to conduct the smallanimal fluorescence imaging experiments of Zn-MPB'L-NO 2 in vivo and explore the fluorescence signal changes over time ( Figure 4A-F).…”

Section: Angewandte Chemiementioning

confidence: 99%

A Cofactor‐Substrate‐Based Supramolecular Fluorescent Probe for the Ultrafast Detection of Nitroreductase under Hypoxic Conditions

Jiao

Zhang²,

Gao

et al. 2020

Angewandte Chemie

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Identifying the location and expression levels of enzymes under hypoxic conditions in cancer cells is vital in early‐stage cancer diagnosis and monitoring. By encapsulating a fluorescent substrate, L‐NO2, within the NADH mimic‐containing metal–organic capsule Zn‐MPB, we developed a cofactor‐substrate‐based supramolecular luminescent probe for ultrafast detection of hypoxia‐related enzymes in solution in vitro and in vivo. The host–guest structure fuses the coenzyme and substrate into one supramolecular probe to avoid control by NADH, switching the catalytic process of nitroreductase from a double‐substrate mechanism to a single‐substrate one. This probe promotes enzyme efficiency by altering the substrate catalytic process and enhances the electron transfer efficiency through an intra‐molecular pathway with increased activity. The enzyme content and fluorescence intensity showed a linear relationship and equilibrium was obtained in seconds, showing potential for early tumor diagnosis, biomimetic catalysis, and prodrug activation.

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Section: Angewandte Chemiementioning

confidence: 99%

A Cofactor‐Substrate‐Based Supramolecular Fluorescent Probe for the Ultrafast Detection of Nitroreductase under Hypoxic Conditions

Jiao

Zhang²,

Gao

et al. 2020

Angewandte Chemie

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“…33 Upon deprotection of the dioxetane by the analyte, it will undergo CIEEL and luminesce. This strategy has been employed for detection of various analytes including hypoxia, [34][35][36] hydrogen sulfide, 37 peroxynitrite, 38 nitroxyl, 39 cathepsin B, 40 -galactosidase, 41,42 formaldehyde, 43 and others. [44][45][46][47][48][49][50][51][52] Chemiluminescence provides many advantages compared to other optical methods in vivo by providing its own light source, thus attenuating autofluorescence and light scattering effects.…”

Section: Introductionmentioning

confidence: 99%

“…53 Chemiluminescent probes have also been shown to achieve much higher fold turnon than comparable fluorophores. 39 Furthermore, they do not Scheme 1. Design and Mechanism of Ratio-pHCL-1.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Ratiometric pH Imaging Using a 1,2-Dioxetane Chemiluminescence Resonance Energy Transfer Sensor

Ryan¹,

Gerberich²,

Haris³

et al. 2020

Preprint

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Regulation of physiological pH is integral for proper whole-body and cellular function, and disruptions in pH homeostasis can be both a cause and effect of disease. In light of this, many methods have been developed to monitor pH in cells and animals. In this study, we report a chemiluminescence resonance energy transfer (CRET) probe Ratio-pHCL-1, comprised of an acrylamide 1,2-dioxetane chemiluminescent scaffold with an appended pH-sensitive carbofluorescein fluorophore. The probe provides an accurate measurement of pH between 6.8-8.4, making it viable tool for measuring pH in biological systems. Further, its ratiometric output is independent of confounding variables. Quantification of pH can be accomplished both using common fluorimetry and advanced optical imaging methods. Using an IVIS Spectrum, pH can be quantified through tissue with Ratio-pHCL-1, which has been shown in vitro and precisely calibrated in sacrificed mouse models. Initial studies showed that intraperitoneal injections of Ratio-pHCL-1 into sacrificed mice produce a photon flux of more than 10^10 photons per second, and showed a significant difference in ratio of emission intensities between pH 6.0, 7.0, and 8.0.

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“…These bright luminophores emit light under physiological conditions with very high efficiency . We and others have utilized these dioxetane luminophores to construct chemiluminescent probes for the detection and imaging of various enzymes and chemical analytes . Such probes are useful for non‐invasive chemiluminescence imaging of living cells and in animals …”

Section: Introductionmentioning

confidence: 99%

“…[10,11] We and othersh ave utilized these dioxetane luminophores to construct chemiluminescent probesf or the detection and imaging of variouse nzymes and chemical analytes. [12][13][14] Such probes are useful for non-invasive chemiluminescence imaging of living cells and in animals. [15][16][17][18][19] Despite this considerable progress, the phenoxy-dioxetane probess uffer from an inherent restriction:T hey can be turnedon only by phenol deprotection.…”

Section: Introductionmentioning

confidence: 99%

Persistent Chemiluminescent Glow of Phenoxy‐dioxetane Luminophore Enables Unique CRET‐Based Detection of Proteases

Hananya

Press

Das

et al. 2019

Chemistry A European J

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Chemiluminescence is being considered an effective imaging modality as it offers low background and high sensitivity. Recent discovery by our group has led to development of new phenoxy‐dioxetane chemiluminescence luminophores, which are highly bright under physiological conditions. However, the current scope of probes based on these luminophores is limited, as they can only be turned on by phenol protecting group removal. Here we present a new chemiluminescence resonance energy transfer (CRET) system, Glow‐CRET, in which light emission is triggered by proteolytic cleavage of a peptide substrate that links a dioxetane luminophore and a quencher. In order to compose such system, a new phenoxy‐dioxetane luminophore, 7‐HC‐CL, was developed. This luminophore exhibits intense and persistent glow chemiluminescence; it undergoes very slow chemiexcitation, and it has the highest chemiluminescence quantum yield ever reported under physiological conditions. Based on 7‐HC‐CL, a Glow‐CRET probe for matrix metalloproteinases, MMP‐CL, was synthesized. Incubation of MMP‐CL with its cognate protease resulted in 160‐fold increase in chemiluminescence signal. MMP‐CL was also able to detect matrix metalloproteinase activity in cancer cells with significantly higher signal‐to‐background ratio than an analogous fluorescence resonance energy transfer (FRET)‐based probe. This work is expected to open new horizons in chemiluminescence imaging, as it enables to use the dioxetanes in ways that had not been possible. We anticipate that 7‐HC‐CL and future derivatives will be utilized not only for the construction of further Glow‐CRET probes, but also for other applications, such as chemiluminescence tagging of proteins.

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A Chemiluminescent Probe for HNO Quantification and Real‐Time Monitoring in Living Cells

Cited by 95 publications

References 58 publications

A Cofactor‐Substrate‐Based Supramolecular Fluorescent Probe for the Ultrafast Detection of Nitroreductase under Hypoxic Conditions

A Cofactor‐Substrate‐Based Supramolecular Fluorescent Probe for the Ultrafast Detection of Nitroreductase under Hypoxic Conditions

Quantitative Ratiometric pH Imaging Using a 1,2-Dioxetane Chemiluminescence Resonance Energy Transfer Sensor

Persistent Chemiluminescent Glow of Phenoxy‐dioxetane Luminophore Enables Unique CRET‐Based Detection of Proteases

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