An activator-induced quencher-detachment-based turn-on probe with a cationic substrate moiety for acetylcholinesterase

Oe, Masahiro; Miki, Koji; Masuda, Akito; Nogita, Kohei; Ohe, Kouichi

doi:10.1039/d1cc05132f

Cited by 12 publications

(15 citation statements)

References 28 publications

(3 reference statements)

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“…We subsequently performed kinetic studies of AChE with Naph-3 and found that Naph-3 serves as the best substrate ( K m = 7.5 μM) for AChE among the three probes tested (Figures C, S7, and Table S2, Supporting Information). Further, to the best of our knowledge, Naph-3 has the lowest K m for AChE among all the reported fluorogenic probes, suggesting that Naph-3 might serve as a better substrate for AChE compared to the reported probes (Table S3, Supporting Information). ,, …”

Section: Resultsmentioning

confidence: 85%

Acetylcholine Structure-Based Small Activatable Fluorogenic Probe for Specific Detection of Acetylcholinesterase

et al. 2023

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Early detection of Alzheimer’s disease (AD) is important for taking proper measures against AD pathogenesis. Acetylcholinesterase (AChE) is widely reported to be associated with the pathogenicity of AD. Here, employing the “acetylcholine-mimic” approach, we designed and synthesized a new class of naphthalimide (Naph)-based fluorogenic probes for specific detection of AChE and avoiding interference of butyrylcholinesterase (BuChE), the pseudocholinesterase. We investigated the action of the probes on Electrophorus electricus AChE, and the native human brain AChE that we expressed in Escherichia coli and purified in the active form for the first time. The probe Naph-3 exhibited a substantial fluorescence enhancement with AChE and majorly avoided BuChE. Naph-3 successfully crossed the cell membrane of the Neuro-2a cells and fluoresced upon reaction with endogenous AChE. We further established that the probe could be effectively used for screening AChE inhibitors. Our study provides a new avenue for the specific detection of AChE, which can be extended to the diagnosis of AChE-related complications.

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Section: Resultsmentioning

confidence: 85%

Acetylcholine Structure-Based Small Activatable Fluorogenic Probe for Specific Detection of Acetylcholinesterase

et al. 2023

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“…1a). Although 6- endo-trig cyclizations should be more favorable than 5- endo-trig , previous attempts at using 6- endo-trig cyclizations to impart fluorogenicity did not lead to more stable cyclic isomers 27–30 . Based on these observations, we hypothesized that a 5- exo-trig cyclization would be a more efficient alternative.…”

Section: Resultsmentioning

confidence: 96%

“…Through the addition of nucleophilic side chains, however, several research groups have attempted to create fluorogenic polymethine dyes. The Ohe group decorated Cy5 and Cy7 dyes with alcohols, amines, and thiols as nucleophiles, thereby forming oxazines, diazines, and thiazines, respectively [27][28][29][30] . The Raymo group developed coumarin-hemicyanine hybrid fluorophores bearing a p-nitrophenol group that exists mainly in the spirocyclic form but can undergo a photoinduced and reversible interconversion into its open fluorescent form 24 .…”

Section: Mainmentioning

confidence: 99%

A general strategy to develop fluorogenic polymethine dyes for bioimaging

Martin

Rivera‐Fuentes

2023

Preprint

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Fluorescence imaging is an invaluable tool to study biological processes and further progress depends on the development of advanced probes. Fluorogenic dyes are crucial to reach intracellular targets and label them with high specificity. Excellent fluorogenic rhodamine dyes have been reported, but they often require a long and low-yielding synthesis and are spectrally limited to the visible range. Here, we present a general strategy to transform polymethine compounds into fluorogenic dyes using an intramolecular ring closure approach. We illustrate the generality of this method by creating both spontaneously blinking and no-wash, turn-on polymethine dyes with emissions across the visible and near-infrared spectrum. These probes are compatible with self-labeling proteins and small-molecule targeting ligands and can be combined with rhodamine-based dyes for multicolor and fluorescence lifetime multiplexing imaging. This strategy provides access to bright, fluorogenic dyes that emit at wavelengths that are significantly more red-shifted than those of existing rhodamine-based dyes.

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“…To evaluate the less‐emissive nature of the probe under neutral conditions, we defined R c value ( R c,abs ) [5b] that was obtained from UV–vis absorption spectra of βC5S‐A as the ratio of the non‐fluorescent closed‐ring form in a neutral buffered solution (pH 7.6) (Table 2). The R c,abs value was calculated using the following equation:

\vcenter{\openup.5em\halign{$\displaystyle{#}$\cr R{_{{\rm c}{\rm \char44 }{\rm abs}}}=1- {\rm A}{_{7.6}}/{\rm A}{_{2.0}}\hfill\cr}}

…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, no fragments are generated during the enzymatic reaction. By using the AiQd mechanism, turn‐on fluorescence probes for carboxyesterases, including acetylcholinesterase, [5b] and aldehyde dehydrogenase 1A1 (ALDH1A1) [5c,d] have been developed. In the case of ALDH1A1‐responsive probe C5S‐A , [5c] a formyl and mercapto group are grafted on a deep‐red cyanine dye Cy5 as an enzyme‐responsive substrate and a fluorescence‐quenching nucleophilic group, respectively (Figure 1b).…”

Section: Introductionmentioning

confidence: 99%

Steric Control in Activator‐Induced Nucleophilic Quencher Detachment‐Based Probes: High‐Contrast Imaging of Aldehyde Dehydrogenase 1A1 in Cancer Stem Cells

Suzuki

Miki

et al. 2022

ChemPlusChem

Self Cite

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Turn‐on fluorescence probes can visualize the enzyme activity with high contrast. We have established a new turn‐on mechanism, activator‐induced nucleophilic quencher detachment (AiQd), and developed AiQd‐based turn‐on fluorescence probes for the detection of enzymes. Herein, we demonstrate that the precise steric control efficiently quenches the fluorescence of AiQd‐based turn‐on probes before the enzymatic transformation. Theoretical calculation appropriately predicted the ratio of the fluorescence‐quenched closed‐ring form of probes. βC5S‐A, which has a sterically demanding methyl group at the β‐position of a fluorescence‐quenching nucleophilic mercapto group, showed a low background signal. βC5S‐A responded to aldehyde dehydrogenase 1A1 (ALDH1A1) with high selectivity, thereby enabling high‐contrast live imaging of cancer stem cells (signal‐to‐noise ratio >10). The ALDH1A1‐responsiveness of βC5S‐A was not significantly affected by amino acids and biological thiols, such as cysteine and glutathione.

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An activator-induced quencher-detachment-based turn-on probe with a cationic substrate moiety for acetylcholinesterase

Abstract: We report a choline ester-grafted turn-on fluorescence probe to detect acetylcholinesterase (AChE) in living cells. AChE-mediated hydrolysis of the choline ester moiety producing carboxylate initiates the activation of Cy5 fluorophore...

Cited by 12 publications

References 28 publications

Acetylcholine Structure-Based Small Activatable Fluorogenic Probe for Specific Detection of Acetylcholinesterase

Acetylcholine Structure-Based Small Activatable Fluorogenic Probe for Specific Detection of Acetylcholinesterase

A general strategy to develop fluorogenic polymethine dyes for bioimaging

Steric Control in Activator‐Induced Nucleophilic Quencher Detachment‐Based Probes: High‐Contrast Imaging of Aldehyde Dehydrogenase 1A1 in Cancer Stem Cells

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