A new tool to assess ceramide bioactivity: 6-bromo-7-hydroxycoumarinyl-caged ceramide

Kim, Young Ah; Ramirez, Daniel M. Carter; Costain, Willard J.; Johnston, Linda J.; Bittman, Robert

doi:10.1039/c1cc12345a

Cited by 32 publications

(45 citation statements)

References 30 publications

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“…The photolysis plots shown are for loss of starting material since the peak due to the product coumarin was broader than that of the caged coumarin. Note that the concomitant production of ceramide has been demonstrated by HPLC-MS in our previous work (Kim et al, 2011). Some photolyses were done in 4-mL quartz cuvettes rotated in the Rayonet reactor.…”

Section: Methodssupporting

confidence: 57%

“…It involves the condensation of phenols with β-ketoesters under acid-catalyzed conditions, which proceeds via electrophilic attack, trans-esterification, and dehydration. For the condensation of methyl 4-chloroacetoacetate 4 with substituted phenols 5 , catalysis by methanesulfonic acid (Hagen et al, 2010; Kim et al, 2011) gave coumarins 6 . Acetates 7 (86–88%) were prepared in the presence of 3 equiv of KF and 1.1 equiv of AcOH in DMF at rt.…”

Section: Resultsmentioning

confidence: 99%

“…The PEGylated coumarin cages 9 were coupled to ceramides via chloroformate intermediates (Suzuki et al, 2003; Kim et al, 2011) in the presence of DIPEA and DMAP at rt to afford Tc-caged compounds 10 – 11 (40% and 29%, respectively) and Btc-caged compounds 12 – 15 (22–31%) without any protecting group manipulation. The yield of the coupling reaction was probably affected by steric hindrance caused by the long fatty acyl chain; however, this route allows a convenient access to a variety of the caged ceramide analogs.…”

Section: Resultsmentioning

confidence: 99%

“…We have recently reported the synthesis of Bhc-caged ceramide analogs and demonstrated that they are compatible with uptake by cells and photorelease of the parent lipid (Kim et al, 2011). We have also shown that photorelease of ceramide can be accomplished with spatial and temporal control for studies of ceramide-induced membrane reorganization in supported bilayers (Ramirez et al, 2013a,b).…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and photochemical properties of PEGylated coumarin-caged ceramides for cell studies

Kim

Day

Lirette

et al. 2016

Chemistry and Physics of Lipids

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Caged ceramide analogues (C6-, C16-, C18-, C22- and C24-Cer) have been prepared by introducing a hydrophilic coumarin-based cage bearing a short polyethylene glycol (PEG) chain. (6-Bromo-7-mTEGylated-coumarin-4-yl)methyl (Btc) caged ceramide showed efficient photo-uncaging to release the parent ceramide upon direct exposure to 350 nm UV light; in contrast (7-mTEGylated-coumarin-4-yl) methyl (Tc) caged ceramide was photolysed more slowly. In preliminary experiments, Btc-caged ceramides were taken up by cells and their photolysis led to decreases in cell viability, but not to activation of caspase enzymes, suggesting that either reactive oxygen species or an alternate caspase-independent pathway may be responsible for the decreases in cell viability caused by photolysis of caged ceramides.

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Section: Methodssupporting

confidence: 57%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis and photochemical properties of PEGylated coumarin-caged ceramides for cell studies

Kim

Day

Lirette

et al. 2016

Chemistry and Physics of Lipids

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“…In an attempt to make the previously reported preparation protocol (Hagen et al, 2010;Hess et al, 2007;Kim et al, 2011;Nadler et al, 2013;Tsien et al, 2000) more efficient, we have performed the initial two synthetic steps using sealed vessel controlled microwave heating. For the initial condensation step an increased reaction temperature of 80°C delivered 6-bromo-4-(chloromethyl)-7-hydroxy-2H-chromen-2-one in only 10 min.…”

Section: Synthesis Of Bhcmoc-12-dogmentioning

confidence: 99%

Optopharmacological control of TRPC channels by coumarin-caged lipids is associated with a phototoxic membrane effect

Tiapko

Bacsa

Cruz

et al. 2016

Sci. China Life Sci.

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Photouncaging of second messengers has been successfully employed to gain mechanistic insight of cellular signaling pathways. One of the most enigmatic processes of ion channel regulation is lipid recognition and lipid-gating of TRPC channels, which represents pivotal mechanisms of cellular Ca 2+ homeostasis. Recently, optopharmacological tools including caged lipid mediators became available, enabling an unprecedented level of temporal and spatial control of the activating lipid species within a cellular environment. Here we tested a commonly used caged ligand approach for suitability to investigate TRPC signaling at the level of membrane conductance and cellular Ca 2+ handling. We report a specific photouncaging artifact that is triggered by the cage structure coumarin at UV illumination. Electrophysiological characterization identified a light-dependent membrane effect of coumarin. UV light (340 nm) as used for photouncaging, initiated a membrane conductance specifically in the presence of coumarin as low as 30 µmol L 1 concentrations. This conductance masked the TRPC3 conductance evoked by photouncaging, while TRPC-mediated cellular Ca 2+ responses were largely preserved. The observed light-induced membrane effects of the released caging moiety may well interfere with certain cellular functions, and prompt caution in using coumarin-caged second messengers in cellular studies.caged diacylglycerols, TRPC channels, Ca 2+ signaling, optopharmacology Citation:Tiapko, O., Bacsa, B., de la Cruz, G.G., Glasnov, T., and Groschner, K. (2016). Optopharmacological control of TRPC channels by coumarin-caged lipids is associated with a phototoxic membrane effect. Sci China Life Sci 59, 802 -810.

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Lichtgesteuerte Werkzeuge

Brieke

Rohrbach

Gottschalk³

et al. 2012

Angewandte Chemie

249

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Die zeitliche und räumliche Kontrolle über chemische und biologische Prozesse spielt eine Schlüsselrolle im Leben, wo das Ganze oft viel mehr ist als die Summe seiner Einzelteile. Trivialerweise bilden die Moleküle einer Zelle noch lange kein lebendiges System aus, wenn sie lediglich willkürlich angeordnet werden. Wenn wir diese Zusammenhänge und die Probleme, die durch Fehlfunktionen entstehen, verstehen wollen, benötigen wir Werkzeuge, mit denen wir komplexe Experimente für diese Fragestellungen entwickeln können. Externe Triggersignale, mit denen wir präzise bestimmen können, wo, wann und in welchem Ausmaß ein Prozess gestartet oder gestoppt wird, sind dafür äußerst wertvoll. Licht ist solch ein ideales Triggersignal: Es ist hoch selektiv und bei richtiger Anwendung unschädlich. Es kann mit gut etablierten Techniken erzeugt und manipuliert werden, und viele Ansätze existieren, um Licht in lebenden Systemen anzuwenden – von Zellen bis zu höheren Organismen. Dieser Aufsatz wird sich mit den aktuellen Entwicklungen der letzten sechs Jahre befassen und die zugrundeliegenden Technologien sowie ihre Anwendungen diskutieren.

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A new tool to assess ceramide bioactivity: 6-bromo-7-hydroxycoumarinyl-caged ceramide

Cited by 32 publications

References 30 publications

Synthesis and photochemical properties of PEGylated coumarin-caged ceramides for cell studies

Synthesis and photochemical properties of PEGylated coumarin-caged ceramides for cell studies

Optopharmacological control of TRPC channels by coumarin-caged lipids is associated with a phototoxic membrane effect

Lichtgesteuerte Werkzeuge

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