Chemoselective ratiometric imaging of protein S-sulfenylation

Tom, Christopher T.M.B.; Crellin, John E.; Motiwala, Hashim F.; Stone, Matthew B.; Davda, Dahvid; Walker, William J.; Kuo, Yu Hsuan; Hernandez, Jeannie L.; Labby, Kristin Jansen; Gomez-Rodriguez, Lyanne; Jenkins, Paul M.; Veatch, Sarah L.; Martin, Brent R.

doi:10.1039/c7cc02285a

Cited by 14 publications

(9 citation statements)

References 29 publications

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“…The nucleophilic C-2 carbon reacts selectively with sulfenic acid, but its application has been limited by the absence of "turnon" fluorescence or fluorogenic response. In 2016, our group identified phenaline-1,3-dione as a chemical scaffold having fluorogenic potential vis-à-vis its reaction with sulfenic acid 17 that was subsequently adapted in the design of a ratiometric fluorescent probe 18 (Fig. 1a and Supplementary Fig.…”

Section: Mainmentioning

confidence: 99%

Reaction-based fluorogenic probes for selective detection of cysteinyl oxidation in living cells

Ferreira

Yang³

et al. 2021

Preprint

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Measuring reactive oxygen, nitrogen and sulfur species in cells is established technology, but turn-on fluorescence tools for detecting the products of their reaction with protein cysteines remain essentially unknown. Toward this goal, here we describe fluorogenic probes for sulfenic acid, a redox modification of protein cysteines inextricably linked to signaling and oxidative stress. The probes, called CysOx1 and CysOx2, are reaction-based, exhibit excellent cell permeability, rapid reactivity, and high selectivity with minimal cytotoxicity. We applied CysOx2 in a cell-based 96-well plate assay to determine whether kinase inhibitors modulate protein S-sulfenylation as well as O-phosphorylation. Analysis of these data revealed an unexpected positive association of S-sulfenylation and inhibition of select kinases within the TK, AGC, and CMGC families including GSK3, a multitasking Ser/Thr kinase and emerging therapeutic target for neurodegenerative and mood disorders. Chemoproteomic mapping of sulfenic acid-modified cysteines in GSK3 inhibitor-treated cells shows that sites of S-oxidation localize to regulatory cysteines within key components of antioxidant defense systems. Our studies with CysOx probes offer up new insights into kinase-inhibitor dependent modulation of sulfenylome dynamics and should accelerate future efforts in the modern era of translational redox medicine.

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Section: Mainmentioning

confidence: 99%

Reaction-based fluorogenic probes for selective detection of cysteinyl oxidation in living cells

Ferreira

Yang³

et al. 2021

Preprint

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“…Oxidant exposure induces sulfenylation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) [ 48 , 49 ]. Peroxide mediated sulfenylation of GAPDH shifts the metabolism of glucose from glycolysis to PPP [ 50 , 51 ]. Since, the inactivation of GAPDH is reversible, this posttranslational modification allows the cell to maintain homeostatic equilibrium by shifting between metabolic function and the redox balance via the production of NADPH [ 21 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Live cell imaging of oxidative stress in human airway epithelial cells exposed to isoprene hydroxyhydroperoxide

et al. 2022

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“…15 was synthesized using a modified literature procedure . 1 H ,3 H -Benzo[ de ]isochromene-1,3-dione (2.03 g, 10.2 mmol, 1.0 equiv) was added to a suspension of anhydrous zinc chloride (4.18 g, 30.7 mmol, 30 equiv) in degassed diethyl malonate (15.6 mL, 16.4 g, 102 mmol, 10 equiv).…”

Section: Methodsmentioning

confidence: 99%

“…15 was synthesized using a modified literature procedure. 33 1H,3H-Benzo[de]isochromene-1,3dione (2.03 g, 10.2 mmol, 1.0 equiv) was added to a suspension of anhydrous zinc chloride (4.18 g, 30.7 mmol, 30 equiv) in degassed diethyl malonate (15.6 mL, 16.4 g, 102 mmol, 10 equiv). The reaction mixture was stirred at 175 °C for 14 h. After cooling to rt, the mixture was diluted with CH 2 Cl 2 (30 mL).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Spiroconjugated Donor−σ–Acceptor Charge-Transfer Dyes: Effect of the π-Subsystems on the Optoelectronic Properties

Wössner

Esser

2020

J. Org. Chem.

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Charge-transfer-based materials with intramolecular donor–acceptor structures are attractive for technological applications. Herein, a series of donor−σ–acceptor dyes has been prepared in a modular approach. The design of these intramolecular charge-transfer dyes is based on the concept of spiroconjugation, which leads to unique materials with special optical properties. The optical transitions are based on intramolecular charge transfer, as shown by solvatochromic measurements and density functional theory (DFT) calculations. Crystallographic, computational, electrochemical, and optical studies were performed to clarify the effect of different perpendicular π-moieties on the optoelectronic properties. Our molecular tuning allowed for the synthesis of molecules exhibiting strong visible-range absorption. The compounds are not fluorescent due to structural changes in the excited state, as revealed by DFT calculations. Finally, our study describes enantiomerically pure spiroconjugated absorber molecules using 1,1′-binaphthyl-2,2′-diol (BINOL) units on the donor part.

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Chemoselective ratiometric imaging of protein S-sulfenylation

Cited by 14 publications

References 29 publications

Reaction-based fluorogenic probes for selective detection of cysteinyl oxidation in living cells

Reaction-based fluorogenic probes for selective detection of cysteinyl oxidation in living cells

Live cell imaging of oxidative stress in human airway epithelial cells exposed to isoprene hydroxyhydroperoxide

Spiroconjugated Donor−σ–Acceptor Charge-Transfer Dyes: Effect of the π-Subsystems on the Optoelectronic Properties

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