A Self‐Immobilizing and Fluorogenic Probe for β‐Lactamase Detection

Mao, Wuyu; Xia, Lingying; Wang, Yaqun; Xie, Hexin

doi:10.1002/asia.201601344

Cited by 47 publications

(34 citation statements)

References 46 publications

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“…Because of these difficulties, considerable efforts have been invested in searching for new improved methods that are sensitive, specific, rapid, and cost‐effective. Following the successful development of β‐lactamase‐responsive chromogenic and fluorogenic molecular probes for the identification of bacterial pathogens, scientists are now actively seeking similar methods for the specific detection of carbapenemase and CPOs.…”

Section: Introductionmentioning

confidence: 99%

Chemiluminescent Carbapenem‐Based Molecular Probe for Detection of Carbapenemase Activity in Live Bacteria

Das

Ihssen²,

Wick³

et al. 2020

Chemistry A European J

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Carbapenemase‐producing organisms (CPOs) pose a severe threat to antibacterial treatment due to the acquisition of antibiotic resistance. This resistance can be largely attributed to the antibiotic‐hydrolyzing enzymes that the bacteria produce. Current carbapenem “wonder drugs”, such as doripenem, ertapenem, meropenem, imipenem, and so on, are resistant to regular β‐lactamases, but susceptible to carbapenemases. Even worse, extended exposure of bacteria to these drugs accelerates the spread of resistance genes. In order to preserve the clinical efficacy of antibacterial treatment, carbapenem drugs should be carefully regulated and deployed only in cases of a CPO infection. Early diagnosis is therefore of paramount importance. Herein, we report the design, synthesis, and activity of the first carbapenemase‐sensitive chemiluminescent probe, CPCL, which may be used to monitor CPO activity. The design of our probe enables enzymatic cleavage of the carbapenem core, which is followed by a facile 1,8‐elimination process and the emission of green light through rapid chemical excitation. We have demonstrated the ability of the probe to detect a number of clinically relevant carbapenemases and the successful identification of CPO present in bacterial cultures, such as those used for clinical diagnosis. We believe that our use of “turn‐on” chemiluminescence activation will find significant application in future diagnostic assays and improve antibacterial treatment.

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Section: Introductionmentioning

confidence: 99%

Chemiluminescent Carbapenem‐Based Molecular Probe for Detection of Carbapenemase Activity in Live Bacteria

Das

Ihssen²,

Wick³

et al. 2020

Chemistry A European J

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“…Early work with enzyme-activated probes was predominately on hydrolase-activated probes, which continue to be important tools for intracellular drug delivery, 64 imaging of dynamic cell processes, 20 as well as diagnostics and therapeutics. 65–67 …”

Section: Hydrolases (Ec 3)mentioning

confidence: 99%

“…67 The nascent electrophile forms covalent bonds with nucleophilic residues of β-lactamase before probe diffusion occurs, enabling spatiotemporal tracking of the enzyme. The utility of this approach was demonstrated in E. coli cells that produce β-lactamase.…”

Section: Hydrolases (Ec 3)mentioning

confidence: 99%

Enzyme-Activated Fluorogenic Probes for Live-Cell and in Vivo Imaging

2018

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Fluorogenic probes, small-molecule sensors that unmask brilliant fluorescence upon exposure to specific stimuli, are powerful tools for chemical biology. Those probes that respond to enzymatic catalysis illuminate the complex dynamics of biological processes at a level of spatiotemporal detail and sensitivity unmatched by other techniques. Here, we review recent advances in enzyme-activated fluorogenic probes for biological imaging. We organize our survey by enzyme classification, with emphasis on fluorophore masking strategies, modes of enzymatic activation, and the breadth of current and future applications. Key challenges such as probe selectivity and spectroscopic requirements are described alongside of therapeutic, diagnostic, and theranostic opportunities.

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“…Along this line, QM has been extensively applieda ss elf-immobilizing imaging reagents for activities of an umber of biologically important enzymes, including phosphatases, [9] glycosidases, [8,10] sulfatases, [11] and b-lactamases. [12] In general,t hese QM-based labelingp robess tructurally consist of four components:e nzymatic recognition moiety,l atent trapping moiety,l inker,a nd reporter ( Figure 1). The latent trapping moiety,t hat is, the precursor of QM, plays ak ey role in the efficiencyo fl abelingc ovalentlyp roteins.C urrently,t wo typeso fQ Ms, o-QMs and p-QMs, are mainly employed as trapping units.…”

Section: Introductionmentioning

confidence: 99%

Highly Efficient Multiple‐Labeling Probes for the Visualization of Enzyme Activities

Song

Chen

et al. 2019

Chemistry A European J

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Quinone methide (QM) as a latent trapping unit has been widely explored in activity‐based self‐immobilizing reagents. However, further application of this strategy has been largely hampered by the limited labeling efficiency to proteins. In this study, a thorough investigation on the labeling efficiency and the structure of QM‐based trapping unit is presented, from which a QM with multiple leaving groups was identified as an optimal trapping unit. An alkaline phosphatase (ALP) immobilizing reagent featured with this multiple‐labeling trapping unit exhibited lower nonspecific binding and, remarkably, a significantly higher labeling efficiency over other immobilizing reagents upon enzymatic activation. The utility of this imaging reagent was further demonstrated with the in vitro and in vivo visualization of the ALP activities. Furthermore, the multiple functional trapping unit may find greater value in the other activity‐based immobilizing probes.

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A Self‐Immobilizing and Fluorogenic Probe for β‐Lactamase Detection

Cited by 47 publications

References 46 publications

Chemiluminescent Carbapenem‐Based Molecular Probe for Detection of Carbapenemase Activity in Live Bacteria

Chemiluminescent Carbapenem‐Based Molecular Probe for Detection of Carbapenemase Activity in Live Bacteria

Enzyme-Activated Fluorogenic Probes for Live-Cell and in Vivo Imaging

Highly Efficient Multiple‐Labeling Probes for the Visualization of Enzyme Activities

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