Skip to main content

Synthetic sulfogalactosylceramide (sulfatide) and its use for the mass spectrometric quantitative urinary determination in metachromatic leukodystrophies

Glycoconjugate Journal volume 25, pages 147–155 (2008)Cite this article

An Erratum to this article was published on 19 September 2007

Abstract

3-O-Sulfogalactosylceramides (sulfatides) accumulate in the genetic disease metachromatic leukodystrophy which is due to a defect in the catabolic enzyme, arylsulfatase A. Clinical diagnosis is usually confirmed by in vitro enzymatic deficiency of arylsulfatase A activity. The diagnosis may be complicated because of arylsulfatase A pseudo-deficiencies and another cause of MLD, sphingolipid activator B deficiency. As large quantities of sulfatides can be found in the urine in this disease, sulfatiduria appears as an extremely useful test. As recently enzyme replacement is underway, the quantitative determination, using an internal standard, appears particularly useful as a follow-up. Thus a non-physiological sulfatide was synthesized for this purpose, i.e. 3-O-sulfo-β-d-C17 galactosylceramide (3-O-Sulfo-d-Galactosyl-β1′→1-N-Heptadecanoyl-d-erythro-Sphingosine). It has been prepared through condensation of an azidosphingosine derivative with a protected d-galactopyranosyltrichloroacetimidate. Reduction of the azide was followed by acylation of a C-17 fatty acid. The key step was achieved by selective sulfation of the desired hydroxyl group on the sugar residue of the galactosylceramide using the stannylene methodology to give a 3′-sulfated beta-galactosyl C-17 ceramide.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Scheme 1
Scheme 2
Scheme 3
Scheme 4
Fig. 1
Scheme 5
Fig. 2

References

  1. Ishizuka, I.: Chemistry and functional distribution of sulfoglycolipids. Prog. Lipid Res. 36, 245–319 (1997)

    PubMed  Article  CAS  Google Scholar 

  2. Hsu, F.F., Bohrer, J., Turk, J.: Electrospray ionization tandem mass spectrometric analysis of sulfatide. Determination of fragmentation patterns and characterization of molecular species in brain and in pancreatic islets. Biochim. Biophys. Acta. 1392, 202–216 (1998)

    PubMed  CAS  Google Scholar 

  3. Colsch, B., Afonso, C., Popa, I., Portoukalian, J., Fournier, F., Tabet, J.C., Baumann, N.: Characterization of the ceramide moieties of sphingoglycolipids from mouse brain by ESI-MS/MS: identification of ceramides containing sphingadienine. J. Lipid Res. 45, 281–286 (2004)

    PubMed  Article  CAS  Google Scholar 

  4. Pernber, Z., Molander-Melin, M., Berthold, C.H., Hansson, E., Fredman, P.: Expression of the myelin and oligodendrocyte progenitor marker sulfatide in neuron and astrocytes of adult rat brain. J. Neurosci. Res. 69, 86–93 (2002)

    PubMed  Article  CAS  Google Scholar 

  5. Blomqvist, M., Osterbye, T., Mansson, J.E., Horn, T., Buschard, K., Fredman, P.: Selective lack of the C16:0 fatty acid isoform of sulfatide in pancreas of type 2 diabetic animal models. APMIS. 112, 867–877 (2003)

    Article  Google Scholar 

  6. Sandhoff, R., Hepbildikler, S.T., Jennemann, R., Geyer, R., Gieselmann, V., Proia, R.L., Herbert Wiegandt, H., Gröne, H.J.: Kidney sulfatides in mouse models of inherited glycosphingolipid disorders. Determination by nano-electrospray ionization tandem mass spectrometry. J. Biol. Chem. 277, 20386–20398 (2002)

    PubMed  Article  CAS  Google Scholar 

  7. Lopate, G., Pestronk, A., Evans, S., Li, L., Clifford, D.: Anti-sulfatide antibodies in HIV-infected individuals with sensory neuropathy. Neurology. 64, 1632–1634 (2005)

    PubMed  Article  CAS  Google Scholar 

  8. Ilyas, A.A., Chen, Z.W., Cook, S.D.: Antibodies to sulfatide in cerebrospinal fluid of patients with multiple sclerosis. J. Neuroimmunol. 139, 76–80 (2003)

    PubMed  Article  CAS  Google Scholar 

  9. Kanter, J.I., Narayana, S., Ho, P.P., Catz, I., Warren, K.G., Sobel, R.A., Steinman, L., Robinson, W.H.: Lipid microarrays identify key mediators of autoimmune brain inflammation. Nat. Med. 12, 138–143 (2006)

    PubMed  Article  CAS  Google Scholar 

  10. Andersson, K., Buschard, K., Fredman, P., Kaas, A., Lidstrom, A.M., Madsbad, S., Mortensen, H., Mansson, J.E.: Patients with insulin-dependent diabetes but not those with non-insulin-dependent diabetes have anti-sulfatide antibodies as determined with a new ELISA assay. Autoimmunity. 35, 463–468 (2002)

    PubMed  Article  Google Scholar 

  11. Von Figura, K., Gieselmann, V., Jaeken, J.: Metachromatic Leukodystrophy. In: Scriver, C.R., Beaudet, A.L., Sly, W., Valle, D., Childs, B., Kinzler, K.W., Vogelstein, B., (eds.) Metabolic Basis of Inherited Disease, 8th ed, vol. 3, pp. 3695–3724. McGraw-Hill, New York (2001)

    Google Scholar 

  12. Rauschka, H., Colsch, B., Baumann, N., Wevers, R., Schmidbauer, M., Krammer, M., Turpin, J.C., Lefevre, M., Olivier, C., Tardieu, S., Krivit, W., Moser, H., Moser, A., Gieselmann, V., Zalc, B., Cox, T., Reuner, U., Tylki-Szymanska, A., Aboul-Enein, F., Leguern, E., Bernheimer, H., Berger, J.: Late onset metachromatic leukodystrophy : genotype strongly influences phenotype. Neurology. 67, 859–863 (2006)

    PubMed  Article  CAS  Google Scholar 

  13. Lugowska, A., Tylki-Szymanska, A., Berger, J., Molzer, B.: Elevated sulfatide excretion in compound heterozygotes of metachromatic leukodystrophy and ASA-pseudodeficiency allele. Clin. Biochem. 30, 325–331 (1997)

    PubMed  Article  CAS  Google Scholar 

  14. Berna, L., Asfaw, B., Conzelmann, E., Cerny, B., Ledvinova, J.: Detemination of urinary sulfatides and other lipids by combination of reversed-phase and thin-layer chromatographies. Anal. Biochem. 269, 304–311 (1999)

    PubMed  Article  CAS  Google Scholar 

  15. Baumann, N., Turpin, J.C., Lefevre, M., Colsch, B.: Motor and psycho-cognitive clinical types in adult metachromatic leukodystrophy : genotype/phenotype relationships? J. Physiol. (Paris). 96, 301–306 (2002)

    Article  Google Scholar 

  16. Whitfield, P.D., Sharp, P.C., Johnson, D.W., Nelson, P., Meikle, P.J.: Characterization of urinary sulfatides in metachromatic leukodystrophy using electrospray-tandem mass spectrometry. Molec. Genet. Metab. 73, 30–37 (2001)

    Article  CAS  Google Scholar 

  17. Rafi, M.A., Coppola, S., Liu, S.L., Rao, H.Z., Wenger, D.A.: Disease-causing mutation in cis with the common arylsulfatase A pseudo-deficiency allele compound the difficulties in accurately identifying patients and carriers of metachromatic leukodystrophy. Mol. Gen. Metab. 79, 83–90 (2003)

    Article  CAS  Google Scholar 

  18. Matzner, U., Herbst, E., Hedayati, K.K., Lullmann-Rauch, R., Wessig, C., Schroder, S., Eistrup, C., Moller, C., Fogh, J., Gieselmann, V.: Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophy. Hum. Mol. Genet. 14, 1139–1152 (2005)

    PubMed  Article  CAS  Google Scholar 

  19. Schmidit, R.R., Zimmermann, P.: Synthesis of D-erythro-sphingosines. Tetrahedron Lett. 27, 481–484 (1986)

    Article  Google Scholar 

  20. Ito, Y., Kiso, M., Hasegawa, A.: Studies on the thioglycosldes of N-acetylneuraminic acid 6: synthesis of ganglioside GM4 analogs. J. Carbohydr. Chem. 8, 285–294 (1989)

    Article  CAS  Google Scholar 

  21. Schmidt, R.R., Michel, J., Roos, M.: Direkte syntese von O-α-und O-β-glycosyl-imidaten. Liebigs. Ann. Chem. 1343–1357 (1984)

  22. Amvam-Zollo, P.H., Sinaÿ, P.: Type XIV polysaccharide: synthesis of a repeating branched tetrasaccharide with dioxa-type spacer-arms. Carbohydr. Res. 150, 199–212 (1986)

    PubMed  Article  CAS  Google Scholar 

  23. Misra, A.K., Agnihotri, G.: Chloramine-T-mediated chemoselective hydrolysis of thioglycosides into glycosyl hemiacetals under neutral conditions. Carbohydr. Res. 339, 885–890 (2004)

    PubMed  Article  CAS  Google Scholar 

  24. Grundler, R., Schmidt, R.R.: Anwendung des trichloracetimidat-verfahrens auf 2-azidoglucose-und 2-azidogalactose-derivate. Liebigs. Ann. Chem. 1826–1847 (1984)

  25. Marinier, A., Martel, A., Banville, J., Bachand, C., Remillard, R., Lapointe, P., Turmel, B., Menard, M., Harte, W.E., Jr., Wright, J.J.K., Todderud, G., Tramposch, K.M., Bajorath, J., Hollenbaugh, D., Aruffo, A.: Sulfated galactocerebrosides as potential antiinflammatory agents. J. Med. Chem. 40, 3234–3247 (1997)

    PubMed  Article  CAS  Google Scholar 

  26. Zimmermann, P., Bommer, R., Bär, T., Schmidt, R.R.: Azidosphingosine glycosylation in glycosphingolipid synthesis. J. Carbohydr. Chem. 7, 435–452 (1988)

    Article  CAS  Google Scholar 

  27. Vaultier, M., Knouzi, N., Carrie, R.: Reduction d’azides en amines primaires par une méthode générale utilisant la réaction de staudinger. Tetrahedron Lett. 24, 763–764 (1983)

    Article  CAS  Google Scholar 

  28. Terada, T., Kiso, M., Hasegawa, A.: Synthesis of KDN-lactotetraosylceramide, KDN-neolactotetraosylceramide, and KDN-Lewis X ganglioside. Carbohydr. Res. 259, 201–218 (1994)

    PubMed  Article  CAS  Google Scholar 

  29. Zhang, Y., Brodzky, A., Sinaÿ, P.: Synthesis of mono-, di- and trisulfated Lewis X trisaccharides. Tetrahedron: Asymmetry. 9, 2451–2464 (1998)

    Article  CAS  Google Scholar 

  30. Gilbert, B., Davis, N.J., Pearce, M., Aplin, R.T., Flitsch, S.L.: Dibutylstannylene acetals: useful intermediates for the regioselective sulfation of glycosides. Tetrahedron: Asymmetry. 5, 2163–2178 (1994)

    Article  Google Scholar 

  31. Guilbert, B., Davis, N.J., Flitsch, S.L.: Regioselective sulfation of disaccharides using dibutylstannylene acetals. Tetrahedron Lett. 35, 6563–6566 (1994)

    Article  CAS  Google Scholar 

  32. Lubineau, A., Le Gallic, J., Lemoine, R.: First synthesis of the 3′-sulfated Lewisa pentasaccharide, the most potent human E-selection ligand so far. Bioorg. Med. Chem. 2, 1143–1151 (1994)

    PubMed  Article  CAS  Google Scholar 

  33. Lubineau, A., Lemoine, R.: Regioselective sulfation of galactose derivatives through the stannylene procedure. New synthesis of the 3′-O-sulfated Lewisa trisaccharide. Tetrahedron Lett. 35, 8795–8796 (1994)

    Article  CAS  Google Scholar 

  34. Uyama, E.I., Kutsukake, Y., Hara, A., Uemura, K., Uchino, M., Mita, S., Ando, M., Taketomi, T.: Abnormal excretion of urinary phospholipids and sulfatide in patients with mitochondrial encephalopathies. Biochem. Biophys. Res. Commun. 194, 266–273 (1993)

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgement

CUI Yanli is grateful to the China Scholarship Council for financial support. COLSCH Benoit gratefully acknowledges the France Alzheimer association for financial support.

Author information

Affiliations

  1. Département de Chimie, Ecole Normale Supérieure, UMR 8642: CNRS-ENS-UPMC, 24 rue Lhomond, 75231, Paris cedex 05, France

    Yanli Cui, Jean-Maurice Mallet & Yongmin Zhang

  2. Department of Chemistry, Zhejiang University, Hangzhou, 310027, China

    Yanli Cui

  3. ZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang University, Hangzhou, 310058, China

    Yongmin Zhang

  4. Université Pierre et Marie Curie, UMR CNRS 7613, 4 Place Jussieu, 75252, Paris cedex 05, France

    Benoit Colsch, Carlos Alonso, Nicole Baumann & Jean-Claude Tabet

  5. Université Pierre et Marie Curie, UMR INSERM 711, Hôpital de la Salpêtrière, 47 Bd de l’Hôpital, 75651, Paris cedex 13, France

    Benoit Colsch & Nicole Baumann

Authors
  1. Yanli Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Benoit Colsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlos Alonso
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicole Baumann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jean-Claude Tabet
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jean-Maurice Mallet
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yongmin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yongmin Zhang.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s10719-007-9072-x

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Cui, Y., Colsch, B., Alonso, C. et al. Synthetic sulfogalactosylceramide (sulfatide) and its use for the mass spectrometric quantitative urinary determination in metachromatic leukodystrophies. Glycoconj J 25, 147–155 (2008). https://doi.org/10.1007/s10719-007-9067-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-007-9067-7

Keywords

  • Sulfatide
  • Glycosphingolipid
  • Mass spectroscopy
  • Galactosyl ceramide