Small-molecule fluorescent probes based on covalent assembly strategy for chemoselective bioimaging

Chen, Xingwei; Huang, Zhongxi; Huang, Lihua; Shen, Qian; Yang, Naidi; Pu, Chibin; Shao, Jinjun; Li, Lin; Huang, Wei

doi:10.1039/d1ra08037g

Cited by 26 publications

(13 citation statements)

References 132 publications

(142 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the field of “covalent‐assembly” fluorescent probes, pioneering works of the Swager (2003) [24] and Anslyn (2005) [25] groups have highlighted the valuable potential of fluorogenic sensing through in situ formation of blue‐emissive 7‐(diethylamino)coumarins (DEACs) from uncyclized precursors and triggered by the species to be detected (Figure 4). Since these early notable achievements, more than 70 examples of “covalent‐assembly” type probes for the detection of a wide range of analytes including biothiols, enzymes, hazardous air pollutants (CO, hydrazine, …), metal cations, reactive anions and ROS/RNS, have been published [13b,26,27] . The vast majority are cinnamate‐ or cinnamonitrile‐like caged precursors bearing a masked hydroxyl group on ortho position.…”

Section: Resultsmentioning

confidence: 99%

Arylidene Meldrum's Acid: A Versatile Structural Motif for the Design of Enzyme‐Responsive “Covalent‐Assembly” Fluorescent Probes with Tailor‐Made Properties**

Renault

Capello

Yao

et al. 2023

Chemistry An Asian Journal

View full text Add to dashboard Cite

Latent cyclic carbon‐centered nucleophiles (latent C‐nucleophiles) are recently proving their value in the field of reaction‐based fluorescent probes, far beyond their primary utility in organic synthesis. They are typically used to introduce a Michael acceptor moiety acting as a recognition/reaction site for analyte to be detected or as a kinetic promoter of fluorogenic cascade reactions triggered by a reactive species. C‐nucleophiles bearing a further reactive handle offer an additional opportunity for tuning the physicochemical/targeting properties or providing drug‐releasing capabilities to these probes, through the covalent attachment of ad hoc chemical moiety. In order to implement such strategy to fluorogenic/chromogenic enzyme substrates based on the “covalent‐assembly” principle, we have explored the potential of some functionalized derivatives of barbituric acid, piperidine‐2,4‐dione and Meldrum's acid. Our investigations based on the rational design and analytical validations of enzyme‐responsive caged precursors of fluorescent pyronin dyes and 7‐(diethylamino)coumarin‐3‐carboxylic acid, led to identify a versatile candidate suitable for this late‐stage structural optimization approach. This Meldrum's acid derivative enables to either enhance water solubility or achieve the reversible conjugation of a targeting ligand, while promoting in situ formation of fluorophore upon enzymatic activation. This study opens the way to novel multifunctional fluorescence imaging probes and optically modulated small conjugate‐based theranostics.

show abstract

Section: Resultsmentioning

confidence: 99%

Arylidene Meldrum's Acid: A Versatile Structural Motif for the Design of Enzyme‐Responsive “Covalent‐Assembly” Fluorescent Probes with Tailor‐Made Properties**

Renault

Capello

Yao

et al. 2023

Chemistry An Asian Journal

View full text Add to dashboard Cite

show abstract

“…However, the great structural plasticity of these molecules is also the source of complex, often highly dynamic tridimensional structures that support highly complex cellular processes, including the catalysis of specific reactions or the specific recognition of molecular targets. In particular, the structural modularity and flexibility of ribonucleic acid (RNA) are exploited at A plethora of fluorogenic chemicals, for instance, exploiting the preferential reactivity of silyl or boronic groups with fluoride has also been described, [16][17][18][19] but none of these compounds is currently commercially available, and most of them have only limited compatibility with biological conditions (e.g., solubility in aqueous media), restricting their direct application for fluoride detection. Although counterintuitive at a first glance, RNA-based biosensors thus represent an attractive alternative in a biological context.…”

Section: Introductionmentioning

confidence: 99%

“…[ 12 ] At present, fluoride is detectable by fluoride‐specific electrodes [ 13,14 ] or colorimetry, [ 15,16 ] but none of these approaches fulfills all the above‐mentioned requirements. A plethora of fluorogenic chemicals, for instance, exploiting the preferential reactivity of silyl or boronic groups with fluoride has also been described, [ 16–19 ] but none of these compounds is currently commercially available, and most of them have only limited compatibility with biological conditions (e.g., solubility in aqueous media), restricting their direct application for fluoride detection. Although counterintuitive at a first glance, RNA‐based biosensors thus represent an attractive alternative in a biological context.…”

Section: Introductionmentioning

confidence: 99%

FluorMango, an RNA‐Based Fluorogenic Biosensor for the Direct and Specific Detection of Fluoride

Husser

Vuilleumier

Ryckelynck

2022

Small

View full text Add to dashboard Cite

an impressive level by riboswitches, a class of RNA motifs mostly found in the 5′ untranslated regions of some bacterial messenger RNAs (mRNAs). These sequences are able to specifically switch their structure in the presence of a target ligand, usually a small molecule, in order to control downstream gene expression (transcription or translation). [1][2][3][4] Riboswitches usually comprise two domains: a sensor aptamer that specifically recognizes a target molecule (with an affinity sometimes exceeding that of antibodies for their antigen), and a regulatory platform that remodels a region of the mRNA to modulate its transcription and/or its translation. The two domains are usually functionally connected by a transducing element, also called communication module. [1] Their modular structure makes riboswitches an excellent starting point for molecular engineering. For instance, exchanging the sensor aptamer domain for another one, natural or synthetic, already enabled the development of engineered riboswitches for application in living cells as well as in cell-free systems. [5][6][7] Thus, using such a construct to control the expression of a reporter gene (e.g., coding for a fluorescent protein, luciferase or another reporting enzyme), would yield a biosensor, that is, a biological molecule (or system) that converts the presence of a specific molecule into a measurable signal. [8] Among the wide palette of potential target ligands for this technology, small negatively charged molecules are expected to be the most difficult to target using RNA-based sensors as they offer only a low number of possible interaction sites and because strong electrostatic repulsion with polyanionic nucleic acids is anticipated. Fluoride, the smallest and the most electronegative anion, represents an extreme case in this context. However, its toxicity and often-problematic levels in drinking water make it a highly relevant target for specific detection. [9] Fluoride is also a potential degradation product of fluorinated compounds, an emerging class of persistent and toxic chemicals. [10] Specific detection of this ion would be useful in the development of high-throughput activity assays for the discovery of defluorination enzymes, of which only a few are currently known. [11] To be applicable, a corresponding sensor should be biocompatible, highly selective, easy to use, nontoxic, commercially available or easy to produce, and generate a fluorescent signal compatible with very high-throughput screening pipelines. [12] At present, fluoride is detectable by fluoride-specific electrodes [13,14] or colorimetry, [15,16] but none of these approaches fulfills all the above-mentioned requirements. Nucleic acids are not only essential actors of cell life but also extremely appealing molecular objects in the development of synthetic molecules for biotechnological application, such as biosensors to report on the presence and concentration of a target ligand by emission of a measurable signal. In this work, FluorMango, a fluorogenic ribonucleic acid...

show abstract

“…Optical probes have been a powerful tool for monitoring and imaging anions, cations, enzymes, and biomolecules in vitro / vivo because of their easy operation, high sensitivity, good selectivity, and noninvasive detection ( Chen et al, 2018a ; Hou et al, 2020 ; Li et al, 2020 ; Park et al, 2020 ; Yang et al, 2020 ; Cui et al, 2021 ; Du et al, 2021 ). At present, a huge amount of fluorescent probes have been developed for the investigation of Cys, Hcy, and GSH in living cells based on cyclization with aldehyde, Michael addition, cleavage of sulfonamide, disulfide, selenium–nitrogen, and sulfonate ester ( Chen et al, 2018b ; Chen et al, 2020 ; Yue et al, 2020 ; Chen et al, 2021a ; Li et al, 2021a ; Zhang et al, 2021a ; Zheng et al, 2021 ; Chen et al, 2022 ). However, owing to the similar structures and reactivities of GSH and Cys/Hcy, simultaneous selective detection of Cys/Hcy and GSH is still a great challenge.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Discrimination of Cys/Hcy and GSH With Simple Fluorescent Probe Under a Single-Wavelength Excitation and its Application in Living Cells, Tumor Tissues, and Zebrafish

Yan

Liu

et al. 2022

Front. Chem.

View full text Add to dashboard Cite

Owing to the important physiological sits of biothiols (Cys, Hcy, and GSH), developing accurate detection methods capable of qualitative and quantitative analysis of biothiols in living systems is needed for understanding the biological profile of biothiols. In this work, we have designed and synthesized a 4′-hydroxy-[1,1′-biphenyl]-4-carbonitrile modified with NBD group-based fluorescent probe, BPN-NBD, for sensitive detection of Cys/Hcy and GSH by dual emission signals via a single-wavelength excitation. BPN-NBD exhibited an obvious blue fluorescence (λmaxem = 475 nm) upon the treatment with GSH and reacted with Cys/Hcy to give a mixed blue-green fluorescence (λmaxem = 475 and 545 nm). Meanwhile, BPN-NDB performed sufficient selectivity, rapid detection (150 s), high sensitivity (0.011 µM for Cys, 0.015 µM for Hcy, and 0.003 µM for GSH) and could work via a single-wavelength excitation to analytes and had the ability to image Cys/Hcy from GSH in living MCF-7 cells, tumor tissues, and zebrafish by exhibiting different fluorescence signals. Overall, this work provided a powerful tool for thiols visualization in biological and medical applications.

show abstract

Small-molecule fluorescent probes based on covalent assembly strategy for chemoselective bioimaging

Abstract: In this review, we comprehensively summarize the recent progress in the development of small molecular fluorescent probes based on the covalent assembly principle. The challenges and perspective in this field are also presented.

Cited by 26 publications

References 132 publications

Arylidene Meldrum's Acid: A Versatile Structural Motif for the Design of Enzyme‐Responsive “Covalent‐Assembly” Fluorescent Probes with Tailor‐Made Properties**

Arylidene Meldrum's Acid: A Versatile Structural Motif for the Design of Enzyme‐Responsive “Covalent‐Assembly” Fluorescent Probes with Tailor‐Made Properties**

FluorMango, an RNA‐Based Fluorogenic Biosensor for the Direct and Specific Detection of Fluoride

Simultaneous Discrimination of Cys/Hcy and GSH With Simple Fluorescent Probe Under a Single-Wavelength Excitation and its Application in Living Cells, Tumor Tissues, and Zebrafish

Contact Info

Product

Resources

About