An activity-based fluorescent sensor for the detection of the phenol sulfotransferase SULT1A1 in living cells

Baglia, Regina A.; Mills, Kira; Mitra, Koushambi; Tutol, Jasmine N.; Ball, Darby; Page, Kierstin; Kallu, Jyothi; Gottipolu, Sriharika; D’Arcy, Sheena; Nielsen, Steven O.; Dodani, Sheel C.

doi:10.1039/d0cb00231c

“…Unfortunately, these fluorescent substrates display poor selectivity and emit short emission wavelength, so these agents cannot be used for sensing target enzyme in living systems or in vivo . Recently, a specific fluorescent probe for SULT1 was designed by modifying 3-hydroxy-1,8-naphthalimide and be used for sensing SULT1 activity in living cells 120 . In future, solid works are needed to develop more practical fluorescent probes for these conjugative enzymes.…”

Section: Optical Substrates For Phase II Drug Metabolizing Enzymesmentioning

confidence: 99%

“… SULT2A1 SULT2A1-F1 183 399 360/450 118 SULT1A3 SULT1A3-F2 6.8 623 360/450 117 SULT1E1 SULT1A3-F3 0.0064 0.158 LC-FD 346/384 119 SULT1 SULT-F1 4 N.A. 340/420 120 …”

Section: Optical Substrates For Phase II Drug Metabolizing Enzymesunclassified

Optical substrates for drug-metabolizing enzymes: Recent advances and future perspectives

Jin

¹

,

Wu

²

,

Wu

³

et al. 2022

Acta Pharmaceutica Sinica B

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Activity‐based Photoacoustic Probes Reveal Elevated Intestinal MGL and FAAH Activity in a Murine Model of Obesity

Lucero

¹

,

Gardner

²

,

Yadav

³

et al. 2022

Angewandte Chemie

0

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Obesity is a chronic health condition characterized by the accumulation of excessive body fat which can lead to and exacerbate cardiovascular disease, type-II diabetes, high blood pressure, and cancer through systemic inflammation. Unfortunately, visualizing key mediators of the inflammatory response, such as monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH), in a selective manner is a profound challenge owing to an overlapping substrate scope that involves arachidonic acid (AA). Specifically, these enzymes work in concert to generate AA, which in the context of obesity, has been implicated to control appetite and energy metabolism. In this study, we developed the first selective activity-based sensing probes to detect MGL (PA-HD-MGL) and FAAH (PA-HD-FAAH) activity via photoacoustic imaging. Activation of PA-HD-MGL and PA-HD-FAAH by their target enzymes resulted in 1.74-fold and 1.59-fold signal enhancements, respectively. Due to their exceptional selectivity profiles and deep-tissue photoacoustic imaging capabilities, these probes were employed to measure MGL and FAAH activity in a murine model of obesity. Contrary to conflicting reports suggesting levels of MGL can be attenuated or elevated, our results support the latter. Indeed, we discovered a marked increase of both targets in the gastrointestinal tract. These key findings set the stage to uncover the role of the endocannabinoid pathway in obesity-mediated inflammation.

show abstract

Activity‐based Photoacoustic Probes Reveal Elevated Intestinal MGL and FAAH Activity in a Murine Model of Obesity

Lucero

¹

,

Gardner

²

,

Yadav

³

et al. 2022

View full text Add to dashboard Cite

Obesity is a chronic health condition characterized by the accumulation of excessive body fat which can lead to and exacerbate cardiovascular disease, type-II diabetes, high blood pressure, and cancer through systemic inflammation. Unfortunately, visualizing key mediators of the inflammatory response, such as monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH), in a selective manner is a profound challenge owing to an overlapping substrate scope that involves arachidonic acid (AA). Specifically, these enzymes work in concert to generate AA, which in the context of obesity, has been implicated to control appetite and energy metabolism. In this study, we developed the first selective activity-based sensing probes to detect MGL (PA-HD-MGL) and FAAH (PA-HD-FAAH) activity via photoacoustic imaging. Activation of PA-HD-MGL and PA-HD-FAAH by their target enzymes resulted in 1.74-fold and 1.59-fold signal enhancements, respectively. Due to their exceptional selectivity profiles and deep-tissue photoacoustic imaging capabilities, these probes were employed to measure MGL and FAAH activity in a murine model of obesity. Contrary to conflicting reports suggesting levels of MGL can be attenuated or elevated, our results support the latter. Indeed, we discovered a marked increase of both targets in the gastrointestinal tract. These key findings set the stage to uncover the role of the endocannabinoid pathway in obesity-mediated inflammation.

show abstract

An activity-based fluorescent sensor for the detection of the phenol sulfotransferase SULT1A1 in living cells

Abstract: Here, we report the development, computational modeling, in vitro enzymology, and biological application of an activity-based fluorescent sensor for the human phenol sulfotransferase SULT1A1.

Cited by 5 publications

References 57 publications

Optical substrates for drug-metabolizing enzymes: Recent advances and future perspectives

Optical substrates for drug-metabolizing enzymes: Recent advances and future perspectives

Activity‐based Photoacoustic Probes Reveal Elevated Intestinal MGL and FAAH Activity in a Murine Model of Obesity

Activity‐based Photoacoustic Probes Reveal Elevated Intestinal MGL and FAAH Activity in a Murine Model of Obesity

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