Glycoconjugate Journal

, Volume 25, Issue 4, pp 335–344 | Cite as

First synthesis of two deoxy Lewisx pentaosyl glycosphingolipids

  • Yun Luo
  • Chafika Gourmala
  • Dengxiang Dong
  • Florent Barbault
  • Botao Fan
  • Yongzhou Hu
  • Yongmin Zhang


The Lewisx–Lewisx interaction has been increasingly studied, using a variety of techniques including nuclear magnetic resonance spectroscopy, mass spectrometry, vesicle adhesion, atomic force microscopy, and surface plasmon resonance spectroscopy. However, the detailed molecular mechanism of these weak, divalent cation dependent interactions remains unclear, and new models are needed to probe the nature of this phenomenon in term of key roles of the different hydroxyl groups on Lewisx trisaccharide determinant involved in the Lewisx–Lewisx interaction. An interesting solution is to synthesize a series of Lewisx pentaosyl glycosphingolipid derivatives in which one of the eight hydroxyl groups of Lewisx trisaccharide is replaced by a hydrogen atom, and to test the adhesion induced by interaction of these derivatives, in order to gain insight into the functions played by the hydroxyl groups of the Lewisx trisaccharide. This article describes the synthesis of 3d-deoxy and 4d-deoxy Lewisx pentaosyl glycosphingolipids, to be used for study of the Lewisx–Lewisx interaction.


Carbohydrate Interaction Lewisx Glycosphingolipid Synthesis 



We thank Dr. Stephen Anderson for assistance in editing of the manuscript. This work is dedicated to Professor Pierre Sinaÿ. We thank the French Embassy in China for a Ph.D fellowship to Y. Luo, the China Scholarship Council and Guizhou University for a Ph.D fellowship to D. Dong. Financial supports from the Centre National de la Recherche Scientifique (CNRS), the Ecole Normale Supérieure (ENS) and the Zhejiang University (ZJU) are gratefully acknowledged.


  1. 1.
    Takeichi M.: Cadherin cell adhesion receptors as a morphogenetic regulator. Science 251, 1451–1455 (1991)PubMedCrossRefGoogle Scholar
  2. 2.
    Hynes R.O.: Integrins: versatility, modulation and signalling in cell adhesion. Cell 69, 11–25 (1992)PubMedCrossRefGoogle Scholar
  3. 3.
    Zheng M., Fang H., Hakomori S.: Functional role of N-glycosylation in α5β1 integrin receptor: De-N-glycosylation induces dissociation or altered association of α5 and β1 subunits and concomitant loss of fibronectin binding activity. J. Biol. Chem. 269, 12325–12331 (1994)PubMedGoogle Scholar
  4. 4.
    Yoshimura M., Ihara Y., Matsuzawa Y., Taniguchi N.: Aberrant glycosylation of E-cadherin enhances cell–cell binding to suppress metastasis. J. Biol. Chem. 271, 13811–13815 (1996)PubMedCrossRefGoogle Scholar
  5. 5.
    Guo H.B., Lee I., Kamar M., Akiyama S.K., Pierce M.: Aberrant N-glycosylation of β1 integrin causes reduced α5β1 integrin clustering and stimulates cell migration. Cancer Res. 62, 6837–6845 (2002)PubMedGoogle Scholar
  6. 6.
    Perillo N.L., Marcus M.E., Baum L.G.: Galectins: versatile modulators of cell adhesion, cell proliferation, and cell death. J. Mol. Med. 76, 402–412 (1998)PubMedCrossRefGoogle Scholar
  7. 7.
    Varki A.: Selectin ligands. Proc. Natl. Acad. Sci. USA 91, 7390–7397 (1994)PubMedCrossRefGoogle Scholar
  8. 8.
    Crocker P.R., Floyd H., Ferguson D.J.P., Nitschke L.: In: Inoue Y., Lee Y.C., Troy F.A. (eds), Sialobiology and other novel forms of glycosylation, pp. 111–20. Gakushin, Osaka, Japan, 1999Google Scholar
  9. 9.
    Hakomori S.: Carbohydrate-to-carbohydrate interaction in basic cell biology: a brief overview. Arch. Biochem. Biophys. 426, 173–181 (2004)PubMedCrossRefGoogle Scholar
  10. 10.
    Hakomori S.: Carbohydrate–carbohydrate interaction as an initial step in cell recognition. Pure Appl Chem 63, 473–482 (1991)CrossRefGoogle Scholar
  11. 11.
    Yoshida C., Heasman J., Golstone K., Vickers L., Wylie C., Expression of the Lewis group carbohydrate antigens during xenopus development. Glycobiology 9, 1323–1330 (1999)CrossRefGoogle Scholar
  12. 12.
    Eggens I., Fenderson B., Toyokuni T., Dean B., Stroud M., Hakomori S.: Specific interaction between Lex and Lex determinants. J. Biol. Chem. 264, 9476–9484 (1989)PubMedGoogle Scholar
  13. 13.
    Kojima N., Fenderson B.A., Stroud M.R., Goldberg R.I., Habermann R., Toyokuni T., Hakomori S.: Further studies on cell adhesion based on Lex–Lex interaction, with new approaches: embryoglycan aggregation of F9 teratocarcinoma cells, and adhesion of various tumour cells based on Lex expression. Glycoconjugate J 11, 238–248 (1994)CrossRefGoogle Scholar
  14. 14.
    Wormald M.R., Edge C.J., Dwek R.A.: The solution conformation of the Lex group. Biochem. Biophys. Res. Commun. 180, 1214–1221 (1991)PubMedCrossRefGoogle Scholar
  15. 15.
    Henry B., Desvaux H., Pristchepa M., Berthault P., Zhang Y., Mallet J.M., Esnault J., Sinaÿ P.: NMR study of a Lewisx pentasaccharide derivative: solution structure and interaction with cations. Carbohydr. Res. 315, 48–62 (1999)PubMedCrossRefGoogle Scholar
  16. 16.
    Geyer A., Gege C., Schmidt R.R.: Carbohydrate–carbohydrate recognition between Lewisx glycoconjugates. Angew. Chem. Int. Ed. 38, 1466–1468 (1999)CrossRefGoogle Scholar
  17. 17.
    Geyer A., Gege C., Schmidt R.R.: Calcium dependent carbohydrate–carbohydrate recognition between Lewisx blood group antigens. Angew. Chem. Int. Ed. 39, 3246–3249 (2000)CrossRefGoogle Scholar
  18. 18.
    Geyer A., Gege C., Schmidt R.R.: Carbohydrate–carbohydrate recognition between Lewisx blood group antigens, mediated by calcium ions. Eur. J. Org. Chem. 2475–2485 (2002)Google Scholar
  19. 19.
    Nodet G., Poggi L., Abergel D., Gourmala C., Dong D., Zhang Y., Mallet J.M., Bodenhausen G., Weak calcium-mediated interactions between Lewisx-related trisaccharides studied by NMR measurements of residual dipolar couplings. J. Am. Chem. Soc. 129, 9080–9085 (2007)PubMedCrossRefGoogle Scholar
  20. 20.
    Siuzdak G., Ichikawa Y., Caulfield T.J., Munoz B., Wong C.H., Nicolaou K.C., Evidence of Ca2+-dependent carbohydrate association through ion spray mass-spectrometry. J. Am. Chem. Soc. 115, 2877–2881 (1993)CrossRefGoogle Scholar
  21. 21.
    Pincet F., Le Bouar T., Zhang Y., Esnault J., Mallet J.M., Perez E., Sinaÿ P.: Ultraweak sugar interactions for transient cell adhesion. Biophys. J. 80, 1354–1358 (2001)PubMedCrossRefGoogle Scholar
  22. 22.
    Gourier C., Pincet F., Perez E., Zhang Y., Mallet J.M., Sinaÿ P.: Specific and non specific interactions involving Lex determinant quantified by lipid vesicle micromanipulation. Glycoconjugate J. 21, 165–174 (2004)CrossRefGoogle Scholar
  23. 23.
    Tromas C., Rojo J., de la Fuente J.M., Barrientos A.G., Garcia R., Penadés S.: Adhesion forces between Lewisx determinant antigen measured by atomic force microscopy. Angew. Chem. Int. Ed. 40, 3052–3055 (2001)CrossRefGoogle Scholar
  24. 24.
    de la Fuente J.M., Eaton P., Barrientos A.G., Menéndez M., Penadés S., Thermodynamic evidence for Ca2+-mediated self-aggregation of Lewisx gold glyconanoparticles. A model for cell adhesion via carbohydrate–carbohydrate interaction. J. Am. Chem. Soc. 127, 6192–6197 (2005)PubMedCrossRefGoogle Scholar
  25. 25.
    Hernaiz M.J., de la Fuente J.M., Barrientos A.G., Penadés S.: A model system mimicking glycosphingolipid clusters to quantify carbohydrate self-interactions by surface plasmon resonance. Angew. Chem. Int. Ed. 41, 1554–1557 (2002)CrossRefGoogle Scholar
  26. 26.
    Boubelik M., Floryk D., Bohata J., Drabevora L., Macak J., Smid F., Draber P.: Lex glycosphingolipids mediated cell aggregation. Glycobiology 8, 139–146 (1998)PubMedCrossRefGoogle Scholar
  27. 27.
    Simpson G.L., Gordon A.H., Lindsay D.M., Promsawan N., Crump M.P., Mulholland K., Hayter B.R., Gallagher T.: Glycosylated foldamers to probe the carbohydrate–carbohydrate interaction. J. Am. Chem. Soc. 128, 10638–10639 (2006)PubMedCrossRefGoogle Scholar
  28. 28.
    Gourier C., Pincet F., Perez E., Zhang Y., Zhu Z., Mallet J.M., Sinaÿ P.: The natural Lewisx bearing lipids promote membrane adhesion. Influence of ceramide on carbohydrate–carbohydrate bond formation. Angew. Chem. Int. Ed. 44, 1683–1687 (2005)CrossRefGoogle Scholar
  29. 29.
    Gourmala C., Zhu Z., Luo Y., Fan B.T., Ghalem S., Hu Y., Zhang Y.: First synthesis of 3’-deoxy Lewisx pentasaccharide, Tetrahedron: Asymmetry 16, 3024–3029 (2005)CrossRefGoogle Scholar
  30. 30.
    Luo Y., Dong D., Barbault F., Fan B.T., Hu Y., Zhang Y.: Total synthesis of 4d-deoxy Lewisx pentasaccharide, Comptes Rendus Chimie. Available online 17 May 2007, DOI  10.1016/j.crci. 2007.03.009.
  31. 31.
    Schmidit R.R., Zimmermann P.: Synthesis of D-erythro-sphingosines. Tetrahedron Lett. 27, 481–484 (1986)CrossRefGoogle Scholar
  32. 32.
    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)CrossRefGoogle Scholar
  33. 33.
    Schmidt R.R.: Glycopeptides, glycolipids, and glycolphospholipids are of special interest as components of membranes. Angew. Chem. Int. Ed. Engl. 25, 212–235 (1986)CrossRefGoogle Scholar
  34. 34.
    Grundler R., Schmidt R.R.: Anwendung des trichloracetimidat-verfahrens auf 2-azidoglucose-und 2-azidogalactose-derivate. Liebigs. Ann. Chem. 1826–1847 (1984)Google Scholar
  35. 35.
    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)CrossRefGoogle Scholar
  36. 36.
    Terada T., Kiso M., Hasegawa A.: Synthesis of KDN-lactotetraosylceramide, KDN-neolactotetraosylceramide, and KDN-Lewisx ganglioside. Carbohydr. Res. 259, 201–218 (1994)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Yun Luo
    • 1
    • 2
    • 3
  • Chafika Gourmala
    • 4
  • Dengxiang Dong
    • 2
    • 3
    • 5
  • Florent Barbault
    • 4
  • Botao Fan
    • 4
  • Yongzhou Hu
    • 1
  • Yongmin Zhang
    • 1
    • 2
    • 3
  1. 1.ZJU–ENS joint laboratory of Medicinal Chemistry, College of Pharmaceutical SciencesZhejiang UniversityHangzhouChina
  2. 2.Département de Chimie, UMR 8642: CNRS–ENS–UPMCEcole Normale SupérieureParis Cedex 05France
  3. 3.Institut de Chimie Moléculaire (FR 2769)Université Pierre et Marie Curie—Paris 6ParisFrance
  4. 4.Interfaces, Traitements, Organisation et Dynamique des Systèmes (ITODYS) CNRS–UMR 7086Université Paris 7—Denis DiderotParisFrance
  5. 5.Guiyang College of Traditional Chinese MedicineGuiyangPeople’s Republic of China

Personalised recommendations