Startseite Lebenswissenschaften Click reactions with functional sphingolipids
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Click reactions with functional sphingolipids

  • Julian Fink und Jürgen Seibel EMAIL logo
Veröffentlicht/Copyright: 19. Juni 2018

Abstract

Sphingolipids and glycosphingolipids can regulate cell recognition and signalling. Ceramide and sphingosine-1-phosphate are major players in the sphingolipid pathways and are involved in the initiation and regulation of signalling, apoptosis, stress responses and infection. Specific chemically synthesised sphingolipid derivatives containing small functionalities like azide or alkyne can mimic the biological properties of natural lipid species, which turns them into useful tools for the investigation of the highly complex sphingolipid metabolism by rapid and selective ‘click chemistry’ using sensitive tags like fluorophores. Subsequent analysis by various fluorescence microscopy techniques or mass spectrometry allows the identification and quantification of the corresponding sphingolipid metabolites as well as the research of associated enzymes. Here we present an overview of recent advances in the synthesis of ceramide and sphingosine analogues for bioorthogonal click reactions to study biosynthetic pathways and localization of sphingolipids for the development of novel therapeutics against lipid-dependent diseases.

Award Identifier / Grant number: SE1410/7-1

Award Identifier / Grant number: SE1410/6-2

Funding statement: The authors are grateful to the Deutsche Forschungsgemeinschaft for funding their work (SE1410/6-2, SE1410/7-1).

References

Adada, M., Luberto, C., and Canals, D. (2016). Inhibitors of the sphingomyelin cycle: sphingomyelin synthases and sphingomyelinases. Chem. Phys. Lipids 197, 45–59.10.1016/j.chemphyslip.2015.07.008Suche in Google Scholar

Airola, M.V. and Hannun, Y.A. (2013). Sphingolipid metabolism and neutral sphingomyelinases. Handb. Exp. Pharmacol. 215, 57–76.10.1007/978-3-7091-1368-4_3Suche in Google Scholar

An, D., Na, C., Bielawski, J., Hannun, Y.A., and Kasper, D.L. (2011). Membrane sphingolipids as essential molecular signals for Bacteroides survival in the intestine. Proc. Natl. Acad. Sci. USA 108, 4666–4671.10.1073/pnas.1001501107Suche in Google Scholar

Bartke, N. and Hannun, Y.A. (2009). Bioactive sphingolipids: metabolism and function. J. Lipid Res. 50, 91–96.10.1194/jlr.R800080-JLR200Suche in Google Scholar

Baumruker, T., Billich, A., and Brinkmann, V. (2007). FTY720, an immunomodulatory sphingolipid mimetic: translation of a novel mechanism into clinical benefit in multiple sclerosis. Expert Opin. Invest. Drugs 16, 283–289.10.1517/13543784.16.3.283Suche in Google Scholar

Bieberich, E., Kawaguchi, T., and Yu, R.K. (2000). N-acylated serinol is a novel ceramide mimic inducing apoptosis in neuroblastoma cells. J. Biol. Chem. 275, 177–181.10.1074/jbc.275.1.177Suche in Google Scholar

Bieberich, E., Hu, B., Silva, J., MacKinnon, S., Yu, R.K., Fillmore, H., Broaddus, W.C., and Ottenbrite, R.M. (2002). Synthesis and characterization of novel ceramide analogs for induction of apoptosis in human cancer cells. Cancer Lett. 181, 55–64.10.1016/S0304-3835(02)00049-6Suche in Google Scholar

Blackman, M.L., Royzen, M., and Fox, J.M. (2008). Tetrazine ligation: fast bioconjugation based on inverse-electron-demand Diels-Alder reactivity. J. Am. Chem. Soc. 130, 13518–13519.10.1021/ja8053805Suche in Google Scholar PubMed PubMed Central

Bockelmann, S., Mina, J.G.M., Korneev, S., Hassan, D.G., Mueller, D., Hilderink, A., Vlieg, H.C., Raijmakers, R., Heck, A.J.R., Haberkant, P., et al. (2018). A search for ceramide binding proteins using bifunctional lipid analogs yields CERT-related protein StarD7. J. Lipid Res. 59, 515–530.10.1194/jlr.M082354Suche in Google Scholar PubMed PubMed Central

Borodzicz, S., Czarzasta, K., Kuch, M., and Cudnoch-Jedrzejewska, A. (2015). Sphingolipids in cardiovascular diseases and metabolic disorders. Lipids Health Dis. 14, 55.10.1186/s12944-015-0053-ySuche in Google Scholar PubMed PubMed Central

Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., Aradhye, S., and Burtin, P. (2010). Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat. Rev. Drug Discov. 9, 883–897.10.1038/nrd3248Suche in Google Scholar PubMed

Butler, A.M., Scotti Buzhardt, M.L., Erdogan, E., Li, S., Inman, K.S., Fields, A.P., and Murray, N.R. (2015). A small molecule inhibitor of atypical protein kinase C signaling inhibits pancreatic cancer cell transformed growth and invasion. Oncotarget 6, 15297–15310.10.18632/oncotarget.3812Suche in Google Scholar PubMed PubMed Central

Cabukusta, B., Kol, M., Kneller, L., Hilderink, A., Bickert, A., Mina, J.G.M., Korneev, S., and Holthuis, J.C.M. (2017). ER residency of the ceramide phosphoethanolamine synthase SMSr relies on homotypic oligomerization mediated by its SAM domain. Sci. Rep. 7, 41290.10.1038/srep41290Suche in Google Scholar PubMed PubMed Central

Collenburg, L., Walter, T., Burgert, A., Muller, N., Seibel, J., Japtok, L., Kleuser, B., Sauer, M., and Schneider-Schaulies, S. (2016). A functionalized sphingolipid analogue for studying redistribution during activation in living T cells. J. Immunol. 196, 3951–3962.10.4049/jimmunol.1502447Suche in Google Scholar PubMed

Dauner, M., Batroff, E., Bachmann, V., Hauck, C.R., and Wittmann, V. (2016). Synthetic glycosphingolipids for live-cell labeling. Bioconjug. Chem. 27, 1624–1637.10.1021/acs.bioconjchem.6b00177Suche in Google Scholar PubMed

Dinkins, M.B., Enasko, J., Hernandez, C., Wang, G., Kong, J., Helwa, I., Liu, Y., Terry, A.V., and Bieberich, E. (2016). Neutral sphingomyelinase-2 deficiency ameliorates Alzheimer’s disease pathology and improves cognition in the 5XFAD mouse. J. Neurosci. 36, 8653–8667.10.1523/JNEUROSCI.1429-16.2016Suche in Google Scholar PubMed PubMed Central

Eich, C., Manzo, C., Keijzer, S.D., Bakker, G.-J., Reinieren-Beeren, I., García-Parajo, M.F., and Cambi, A. (2016). Changes in membrane sphingolipid composition modulate dynamics and adhesion of integrin nanoclusters. Sci. Rep. 6, 20693.10.1038/srep20693Suche in Google Scholar PubMed PubMed Central

Erdmann, R.S., Takakura, H., Thompson, A.D., Rivera-Molina, F., Allgeyer, E.S., Bewersdorf, J., Toomre, D., and Schepartz, A. (2014). Super-resolution imaging of the Golgi in live cells with a bioorthogonal ceramide probe. Angew. Chem. Int. Ed. 53, 10242–10246.10.1002/anie.201403349Suche in Google Scholar PubMed PubMed Central

Gaebler, A., Milan, R., Straub, L., Hoelper, D., Kuerschner, L., and Thiele, C. (2013). Alkyne lipids as substrates for click chemistry-based in vitro enzymatic assays. J. Lipid Res. 54, 2282–2290.10.1194/jlr.D038653Suche in Google Scholar PubMed PubMed Central

Gaebler, A., Penno, A., Kuerschner, L., and Thiele, C. (2016). A highly sensitive protocol for microscopy of alkyne lipids and fluorescently tagged or immunostained proteins. J. Lipid Res. 57, 1934–1947.10.1194/jlr.D070565Suche in Google Scholar PubMed PubMed Central

Garrido, M., Abad, J.L., Fabriàs, G., Casas, J., and Delgado, A. (2015). Azide-tagged sphingolipids: new tools for metabolic flux analysis. ChemBioChem 16, 641–650.10.1002/cbic.201402649Suche in Google Scholar

Gerl, M.J., Bittl, V., Kirchner, S., Sachsenheimer, T., Brunner, H.L., Lüchtenborg, C., Özbalci, C., Wiedemann, H., Wegehingel, S., Nickel, W., et al. (2016). Sphingosine-1-phosphate lyase deficient cells as a tool to study protein lipid interactions. PLoS One 11, e0153009.10.1371/journal.pone.0153009Suche in Google Scholar

Gulbins, E. and Kolesnick, R. (2003). Raft ceramide in molecular medicine. Oncogene 22, 7070.10.1038/sj.onc.1207146Suche in Google Scholar

Gutmann, M., Memmel, E., Braun, A.C., Seibel, J., Meinel, L., and Luhmann, T. (2016). Biocompatible azide-alkyne “click” reactions for surface decoration of glyco-engineered cells. ChemBioChem 17, 866–875.10.1002/cbic.201500582Suche in Google Scholar

Haberkant, P., Stein, F., Höglinger, D., Gerl, M.J., Brügger, B., Van Veldhoven, P.P., Krijgsveld, J., Gavin, A.-C., and Schultz, C. (2016). Bifunctional sphingosine for cell-based analysis of protein-sphingolipid interactions. ACS Chem. Biol. 11, 222–230.10.1021/acschembio.5b00810Suche in Google Scholar

Hannun, Y.A., Loomis, C.R., Merrill, A.H., and Bell, R.M. (1986). Sphingosine inhibition of protein kinase C activity and of phorbol dibutyrate binding in vitro and in human platelets. J. Biol. Chem. 261, 12604–12609.10.1016/S0021-9258(18)67133-9Suche in Google Scholar

Heung, L.J., Luberto, C., and Del Poeta, M. (2006). Role of sphingolipids in microbial pathogenesis. Infect. Immun. 74, 28–39.10.1128/IAI.74.1.28-39.2006Suche in Google Scholar PubMed PubMed Central

Hla, T. and Dannenberg, A.J. (2012). Sphingolipid signaling in metabolic disorders. Cell Metab. 16, 420–434.10.1016/j.cmet.2012.06.017Suche in Google Scholar PubMed PubMed Central

Höglinger, D., Nadler, A., Haberkant, P., Kirkpatrick, J., Schifferer, M., Stein, F., Hauke, S., Porter, F.D., and Schultz, C. (2017). Trifunctional lipid probes for comprehensive studies of single lipid species in living cells. Proc. Natl. Acad. Sci. USA 114, 1566–1571.10.1073/pnas.1611096114Suche in Google Scholar PubMed PubMed Central

Homann, A., Qamar, R.-U., Serim, S., Dersch, P., and Seibel, J. (2010). Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid. Beilstein J. Org. Chem. 6, 24.10.3762/bjoc.6.24Suche in Google Scholar PubMed PubMed Central

Hoyle, C.E. and Bowman, C.N. (2010). Thiol-ene click chemistry. Angew. Chem. Int. Ed. 49, 1540–1573.10.1002/anie.200903924Suche in Google Scholar

Huisgen, R. (1961). Centenary Lecture – 1,3-dipolar cycloadditions. Proc. Chem. Soc. 357–396.Suche in Google Scholar

Huisgen, R. (1963). 1,3-Dipolar cycloadditions. Past and future. Angew. Chem. Int. Ed. 2, 565–598.10.1002/anie.196305651Suche in Google Scholar

Jain, A., Beutel, O., Ebell, K., Korneev, S., and Holthuis, J.C.M. (2017). Diverting CERT-mediated ceramide transport to mitochondria triggers Bax-dependent apoptosis. J. Cell. Sci. 130, 360–371.10.1242/jcs.194191Suche in Google Scholar

Jervis, P.J., Cox, L.R., and Besra, G.S. (2011). Synthesis of a versatile building block for the preparation of 6-N-derivatized α-galactosyl ceramides: rapid access to biologically active glycolipids. J. Org. Chem. 76, 320–323.10.1021/jo102064pSuche in Google Scholar

Jervis, P.J., Moulis, M., Jukes, J.-P., Ghadbane, H., Cox, L.R., Cerundolo, V., and Besra, G.S. (2012). Towards multivalent CD1d ligands: synthesis and biological activity of homodimeric α-galactosyl ceramide analogues. Carbohydr. Res. 356, 152–162.10.1016/j.carres.2012.02.034Suche in Google Scholar

Kecheng, Z. and Tomas, B. (2015). Trafficking and functions of bioactive sphingolipids: lessons from cells and model membranes. Lipid Insights 8, 11–20.10.4137/LPI.S31615Suche in Google Scholar

Kolb, H.C., Finn, M.G., and Sharpless, K.B. (2001). Click chemistry: diverse chemical function from a few good reactions. Angew. Chem. Int. Ed. 40, 2004–2021.10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5Suche in Google Scholar

Kolter, T. and Sandhoff, K. (2006). Sphingolipid metabolism diseases. Biochim. Biophys. Acta 1758, 2057–2079.10.1016/j.bbamem.2006.05.027Suche in Google Scholar

Kong, J.N., Hardin, K., Dinkins, M., Wang, G., He, Q., Mujadzic, T., Zhu, G., Bielawski, J., Spassieva, S., and Bieberich, E. (2015). Regulation of Chlamydomonas flagella and ependymal cell motile cilia by ceramide-mediated translocation of GSK3. Mol. Biol. Cell 26, 4451–4465.10.1091/mbc.E15-06-0371Suche in Google Scholar

Kong, J.-N., Zhu, Z., Itokazu, Y., Wang, G., Dinkins, M.B., Zhong, L., Lin, H.-P., Elsherbini, A., Leanhart, S., Jiang, X., et al. (2018). Novel function of ceramide for regulation of mitochondrial ATP release in astrocytes. J. Lipid Res. 59, 488–506.10.1194/jlr.M081877Suche in Google Scholar

Krishnamurthy, K., Dasgupta, S., and Bieberich, E. (2007). Development and characterization of a novel anti-ceramide antibody. J. Lipid Res. 48, 968–975.10.1194/jlr.D600043-JLR200Suche in Google Scholar

Letschert, S., Göhler, A., Franke, C., Bertleff-Zieschang, N., Memmel, E., Doose, S., Seibel, J., and Sauer, M. (2014). Super-resolution imaging of plasma membrane glycans. Angew. Chem. Int. Ed. 53, 10921–10924.10.1002/anie.201406045Suche in Google Scholar PubMed

Leypoldt, F., Munchau, A., Moeller, F., Bester, M., Gerloff, C., and Heesen, C. (2009). Hemorrhaging focal encephalitis under fingolimod (FTY720) treatment: a case report. Neurology 72, 1022–1024.10.1212/01.wnl.0000344567.51394.e3Suche in Google Scholar PubMed

Li, W., Sandhoff, R., Kono, M., Zerfas, P., Hoffmann, V., Ding, B.C.-H., Proia, R.L., and Deng, C.-X. (2007). Depletion of ceramides with very long chain fatty acids causes defective skin permeability barrier function, and neonatal lethality in ELOVL4 deficient mice. Int. J. Biol. Sci. 3, 120–128.10.7150/ijbs.3.120Suche in Google Scholar PubMed PubMed Central

Liang, L. and Astruc, D. (2011). The copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) “click” reaction and its applications. An overview. Coord. Chem. Rev. 255, 2933–2945.10.1016/j.ccr.2011.06.028Suche in Google Scholar

Lipsky, N.G. and Pagano, R.E. (1985). A vital stain for the Golgi apparatus. Science 228, 745–747.10.1126/science.2581316Suche in Google Scholar PubMed

Liu, Y. and Bittman, R. (2006). Synthesis of fluorescent lactosylceramide stereoisomers. Chem. Phys. Lipids 142, 58–69.10.1016/j.chemphyslip.2006.03.001Suche in Google Scholar PubMed

Liu, Y., Xu, X., Gao, Q., Yan, S., Li, Y., and Ding, N. (2017). Rapid access to 6″-functionalized α-galactosyl ceramides by using 2-naphthylmethyl ether as the permanent protecting group. Bioorganic Med. Chem. Lett. 27, 1795–1798.10.1016/j.bmcl.2017.02.055Suche in Google Scholar PubMed

Makiyama, T., Nakamura, H., Nagasaka, N., Yamashita, H., Honda, T., Yamaguchi, N., Nishida, A., and Murayama, T. (2015). Trafficking of acetyl-C16-ceramide-NBD with long-term stability and no cytotoxicity into the Golgi complex. Traffic 16, 476–492.10.1111/tra.12265Suche in Google Scholar PubMed

Merrill, A.H., Sullards, M.C., Allegood, J.C., Kelly, S., and Wang, E. (2005). Sphingolipidomics: high-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. Methods 36, 207–224.10.1016/j.ymeth.2005.01.009Suche in Google Scholar PubMed

Merrill, A.H., Stokes, T.H., Momin, A., Park, H., Portz, B.J., Kelly, S., Wang, E., Sullards, M.C., and Wang, M.D. (2009). Sphingolipidomics: a valuable tool for understanding the roles of sphingolipids in biology and disease. J. Lipid Res. 50, S97–S102.10.1194/jlr.R800073-JLR200Suche in Google Scholar PubMed PubMed Central

Olsen, I. and Jantzen, E. (2001). Sphingolipids in bacteria and fungi. Anaerobe 7, 103–112.10.1006/anae.2001.0376Suche in Google Scholar

Olson, D.K., Frohlich, F., Farese, R.V., Jr., and Walther, T.C. (2016). Taming the sphinx: mechanisms of cellular sphingolipid homeostasis. Biochim. Biophys. Acta 1861, 784–792.10.1016/j.bbalip.2015.12.021Suche in Google Scholar

Patalag, L.J., Sibold, J., Schutte, O.M., Steinem, C., and Werz, D.B. (2017). Gb3 Glycosphingolipids with fluorescent oligoene fatty acids: synthesis and phase behavior in model membranes. ChemBioChem 18, 2171–2178.10.1002/cbic.201700414Suche in Google Scholar

Peng, T., Yuan, X., and Hang, H.C. (2014). Turning the spotlight on protein-lipid interactions in cells. Curr. Opin. Chem. Biol. 21, 144–153.10.1016/j.cbpa.2014.07.015Suche in Google Scholar

Pérez, A.J. and Bode, H.B. (2014). ω-Azido fatty acids as probes to detect fatty acid biosynthesis, degradation, and modification. J. Lipid Res. 55, 1897–1901.10.1194/jlr.M047969Suche in Google Scholar

Pérez, A.J. and Bode, H.B. (2015). “Click chemistry” for the simple determination of fatty acid uptake and degradation: revising the role of fatty acid transporters. ChemBioChem 16, 1588–1591.10.1002/cbic.201500194Suche in Google Scholar

Pewzner-Jung, Y., Tavakoli Tabazavareh, S., Grassmé, H., Becker, K.A., Japtok, L., Steinmann, J., Joseph, T., Lang, S., Tuemmler, B., Schuchman, E.H., et al. (2014). Sphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa. EMBO Mol. Med. 6, 1205–1214.10.15252/emmm.201404075Suche in Google Scholar

Pinto, S.N., Silva, L.C., Futerman, A.H., and Prieto, M. (2011). Effect of ceramide structure on membrane biophysical properties: the role of acyl chain length and unsaturation. Biochim. Biophys. Acta Biomembr. 1808, 2753–2760.10.1016/j.bbamem.2011.07.023Suche in Google Scholar

Rasmussen, J.-A.M. and Hermetter, A. (2008). Chemical synthesis of fluorescent glycero- and sphingolipids. Prog. Lipid Res. 47, 436–460.10.1016/j.plipres.2008.05.002Suche in Google Scholar

Rostovtsev, V.V., Green, L.G., Fokin, V.V., and Sharpless, K.B. (2002). A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew. Chem. Int. Ed. 41, 2596–2599.10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4Suche in Google Scholar

Sandbhor, M.S., Key, J.A., Strelkov, I.S., and Cairo, C.W. (2009). A modular synthesis of alkynyl-phosphocholine headgroups for labeling sphingomyelin and phosphatidylcholine. J. Org. Chem. 74, 8669–8674.10.1021/jo901824hSuche in Google Scholar PubMed

Schenck, M., Carpinteiro, A., Grassmé, H., Lang, F., and Gulbins, E. (2007). Ceramide: physiological and pathophysiological aspects. Arch. Biochem. Biophys. 462, 171–175.10.1016/j.abb.2007.03.031Suche in Google Scholar PubMed

Schiffmann, R. (2015). The consequences of genetic and pharmacologic reduction in sphingolipid synthesis. J. Inherit. Metab. Dis. 38, 77–84.10.1007/s10545-014-9758-8Suche in Google Scholar PubMed

Schoenebeck, F., Ess, D.H., Jones, G.O., and Houk, K.N. (2009). Reactivity and regioselectivity in 1,3-dipolar cycloadditions of azides to strained alkynes and alkenes: a computational study. J. Am. Chem. Soc. 131, 8121–8133.10.1021/ja9003624Suche in Google Scholar PubMed

Schwarzmann, G., Arenz, C., and Sandhoff, K. (2014). Labeled chemical biology tools for investigating sphingolipid metabolism, trafficking and interaction with lipids and proteins. Biochim. Biophys. Acta Mol. Cell. Biol. Lipids 1841, 1161–1173.10.1016/j.bbalip.2013.12.011Suche in Google Scholar PubMed

Singh, A. and Del Poeta, M. (2016). Sphingolipidomics: an important mechanistic tool for studying fungal pathogens. Front. Microbiol. 7, 501.10.3389/fmicb.2016.00501Suche in Google Scholar PubMed PubMed Central

Sletten, E.M. and Bertozzi, C.R. (2009). Bioorthogonale Chemie – oder: in einem Meer aus Funktionalität nach Selektivität fischen. Angew. Chem. 121, 7108–7133.10.1002/ange.200900942Suche in Google Scholar

Takakura, H., Zhang, Y., Erdmann, R.S., Thompson, A.D., Lin, Y., McNellis, B., Rivera-Molina, F., Uno, S.-N., Kamiya, M., Urano, Y., et al. (2017). Long time-lapse nanoscopy with spontaneously blinking membrane probes. Nat. Biotechnol. 35, 773–780.10.1038/nbt.3876Suche in Google Scholar PubMed PubMed Central

Thiele, C., Papan, C., Hoelper, D., Kusserow, K., Gaebler, A., Schoene, M., Piotrowitz, K., Lohmann, D., Spandl, J., Stevanovic, A., et al. (2012). Tracing fatty acid metabolism by click chemistry. ACS Chem. Biol. 7, 2004–2011.10.1021/cb300414vSuche in Google Scholar PubMed

Tornoe, C.W., Christensen, C., and Meldal, M. (2002). Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J. Org. Chem. 67, 3057–3064.10.1021/jo011148jSuche in Google Scholar PubMed

Uno, S.-N., Kamiya, M., Yoshihara, T., Sugawara, K., Okabe, K., Tarhan, M.C., Fujita, H., Funatsu, T., Okada, Y., Tobita, S., et al. (2014). A spontaneously blinking fluorophore based on intramolecular spirocyclization for live-cell super-resolution imaging. Nat. Chem. 6, 681–689.10.1038/nchem.2002Suche in Google Scholar PubMed

Walter, T., Collenburg, L., Japtok, L., Kleuser, B., Schneider-Schaulies, S., Muller, N., Becam, J., Schubert-Unkmeir, A., Kong, J.N., Bieberich, E., et al. (2016). Incorporation and visualization of azido-functionalized N-oleoyl serinol in Jurkat cells, mouse brain astrocytes, 3T3 fibroblasts and human brain microvascular endothelial cells. Chem. Commun. 52, 8612–8614.10.1039/C6CC02879ASuche in Google Scholar PubMed PubMed Central

Walter, T., Schlegel, J., Burgert, A., Kurz, A., Seibel, J., and Sauer, M. (2017). Incorporation studies of clickable ceramides in Jurkat cell plasma membranes. Chem. Commun. 53, 6836–6839.10.1039/C7CC01220ASuche in Google Scholar PubMed

Wang, G., Silva, J., Krishnamurthy, K., Tran, E., Condie, B.G., and Bieberich, E. (2005). Direct binding to ceramide activates protein kinase Cζ before the formation of a pro-apoptotic complex with PAR-4 in differentiating stem cells. J. Biol. Chem. 280, 26415–26424.10.1074/jbc.M501492200Suche in Google Scholar PubMed

Wong, L., Tan, S.S.L., Lam, Y., and Melendez, A.J. (2009). Synthesis and evaluation of sphingosine analogues as inhibitors of sphingosine kinases. J. Med. Chem. 52, 3618–3626.10.1021/jm900121dSuche in Google Scholar PubMed

Wymann, M.P. and Schneiter, R. (2008). Lipid signalling in disease. Nat. Rev. Mol. Cell Biol. 9, 162–176.10.1038/nrm2335Suche in Google Scholar PubMed

Xie, R., Dong, L., Du, Y., Zhu, Y., Hua, R., Zhang, C., and Chen, X. (2016). In vivo metabolic labeling of sialoglycans in the mouse brain by using a liposome-assisted bioorthogonal reporter strategy. Proc. Natl. Acad. Sci. USA 113, 5173–5178.10.1073/pnas.1516524113Suche in Google Scholar PubMed PubMed Central

Received: 2018-02-26
Accepted: 2018-04-15
Published Online: 2018-06-19
Published in Print: 2018-09-25

©2018 Walter de Gruyter GmbH, Berlin/Boston

Heruntergeladen am 10.12.2025 von https://www.degruyterbrill.com/document/doi/10.1515/hsz-2018-0169/pdf
Button zum nach oben scrollen