A Strategy for Specific Fluorescence Imaging of Monoamine Oxidase A in Living Cells

Wu, Xiaofeng; Li, Xiaohua; Ma, Huimin

doi:10.1002/ange.201708428

Cited by 18 publications

(7 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fluorescence probes for monoamine oxidases (MAOs), which are FAD dependent amine oxidases same as LSD1, have been reported, whose detecting strategies are based on an amine oxidation followed by b-elimination mechanism. (26)(27)(28) Generally, MAO florescence probes consist of amine, propyl linker, and fluorophore moieties, and are firstly oxidized by MAOs to generate imine, which is subsequently hydrolyzed by H 2 O to form aldehydes. Then, b-elimination reaction rapidly occurs and the fluorophore is released along with the generations of acrolein and ammonia, resulting in fluorescence increment.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of artificial substrate based on inhibitor for detecting LSD1 activity

Ohta

Kawaguchi

Ieda

et al. 2020

J. Clin. Biochem. Nutr.

View full text Add to dashboard Cite

Lysine methylation is one of the most important modification, which is regulated by histone lysine methyltransferases and histone lysine demethylases. Lysine-specific demethylase 1 (LSD1) specifically demethylates mono- and dimethyl-lysine on histone H3 (H3K4Me/Me 2 , H3K9Me/Me 2 ) to control chromatin structure, resulting in transcriptional repression or activation of target genes. Furthermore, LSD1 is overexpressed in various cancers. Therefore, LSD1 inhibitors would be not only potential therapeutic agents for cancers but also chemical tools to research biological significance of LSD1 in physiological and pathological events. However, known assay methods to date have some inherent drawbacks. The development of simple method in detecting LSD1 activity has been indispensable to identify useful inhibitors. In this study, we designed and synthesized artificial substrates based on inhibitors of LSD1 to examine LSD1 activity by an absorption increment.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis of artificial substrate based on inhibitor for detecting LSD1 activity

Ohta

Kawaguchi

Ieda

et al. 2020

J. Clin. Biochem. Nutr.

View full text Add to dashboard Cite

show abstract

“…23,24 Indeed, fluorogenic probes and masking groups are often inspired by prodrug and inhibitor design strategies. 15,25,26 …”

Section: Probe Designmentioning

confidence: 99%

“…Although probes for the three main enzyme classes EC 1–EC 3 have existed for several decades, recent advances in probe chemistry and design have rejuvenated the field with methods to tune spectroscopic properties and enzyme specificity. 15,17,26 …”

Section: Enzyme Targetsmentioning

confidence: 99%

“…29 Two-photon excited probes 4 and 5 were developed recently to monitor MAO-A and MAO-B activity selectively in deep-tissue imaging. 15,26 Probe 4 is based on a resorufin scaffold with a linker connecting the fluorophore and propylamine enzyme-reactive moiety. MAO-A specificity is conferred by the ortho -halogenated linker, which is inspired by the MAO-A inhibitor clorgiline and also serves as an auto-immolative linker that undergoes elimination to release a quinone methide.…”

Section: Oxidoreductases (Ec 1)mentioning

confidence: 99%

See 1 more Smart Citation

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

2018

View full text Add to dashboard Cite

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.

show abstract

“…Fluorescent probes afford a powerful tool for detection of various enzyme activities in vitro and in living cells. − Currently, fluorescent probes for HDAC could be classified into two groups based on their design strategies, “always-on” probes and “turn-on” probes. The “always-on” probes were designed by tagging a fluorophore to HDACs targeting molecules such as inhibitors or subtrates. − These probes require tedious washing steps to avoid background fluorescence from nonspecifically bound or excessive probes, precluding real-time intracellular HDAC activity detection.…”

mentioning

confidence: 99%

Activatable Fluorescence Probe via Self-Immolative Intramolecular Cyclization for Histone Deacetylase Imaging in Live Cells and Tissues

et al. 2018

View full text Add to dashboard Cite

Histone deacetylases (HDACs) play essential roles in transcription regulation and are valuable theranostic targets. However, there are no activatable fluorescent probes for imaging of HDAC activity in live cells. Here, we develop for the first time a novel activatable two-photon fluorescence probe that enables in situ imaging of HDAC activity in living cells and tissues. The probe is designed by conjugating an acetyl-lysine mimic substrate to a masked aldehyde-containing fluorophore via a cyanoester linker. Upon deacetylation by HDAC, the probe undergoes a rapid self-immolative intramolecular cyclization reaction, producing a cyanohydrin intermediate that is spontaneously rapidly decomposed into the highly fluorescent aldehyde-containing two-photon fluorophore. The probe is shown to exhibit high sensitivity, high specificity, and fast response for HDAC detection in vitro. Imaging studies reveal that the probe is able to directly visualize and monitor HDAC activity in living cells. Moreover, the probe is demonstrated to have the capability of two-photon imaging of HDAC activity in deep tissue slices up to 130 μm. This activatable fluorescent probe affords a useful tool for evaluating HDAC activity and screening HDAC-targeting drugs in both live cell and tissue assays.

show abstract

A Strategy for Specific Fluorescence Imaging of Monoamine Oxidase A in Living Cells

Cited by 18 publications

References 32 publications

Synthesis of artificial substrate based on inhibitor for detecting LSD1 activity

Synthesis of artificial substrate based on inhibitor for detecting LSD1 activity

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

Activatable Fluorescence Probe via Self-Immolative Intramolecular Cyclization for Histone Deacetylase Imaging in Live Cells and Tissues

Contact Info

Product

Resources

About