Synthesis and characterisation of novel glycoclusters based on cell penetrating heptakis(6-aminoethylamino-6-deoxy)-β-cyclodextrin

Original article


The modification of a polyamino βCD, heptakis(6-aminoethylamino-6-deoxy)-βCD (bpen) with several monosaccharides (Man, GlcNAc, Gal, Glc), specific for bacterial lectin targeting is described. The first synthetic approach, based on disuccinimidyl carbonate-substituted monosaccharides had moderate success, whereas the second approach, based on thiopropanoic acid-linked monosaccharides, was more efficient. Each method gave the best result with a different monosaccharide. Given that bpen is known to penetrate cells, the new products are expected to possess both lectin recognition ability and membrane crossing properties.


Monosaccharides Amino cyclodextrin Glycoclusters Cell penetrating 



Funding by the program PENED 2003 (25% Greek GSRT, 75% EU) and Pharmaten S.A., as well as partial funding by the Marie Curie ITN CYCLON (project #237962) is kindly acknowledged.


  1. 1.
    Sharon, N.: Carbohydrates as future anti-adhesion drugs for infectious diseases. Biochim. Biophys. Acta 1760, 527–537 (2006)Google Scholar
  2. 2.
    Vargas-Berenguel, A., Ortega-Caballero, F., Casas-Solvas, J.M.: Supramolecular chemistry of carbohydrate clusters with cores having guest binding abilities. Mini-Rev. Org. Chem. 4, 1–14 (2007)CrossRefGoogle Scholar
  3. 3.
    Gómez-Garcia, M., Benito, J.M., Rodriguez-Lucena, D., Yu, J.-X., Ortiz Mellet, C., Gutierrez Gallego, R., Chmurski, K., Maestre, A., Defaye, J., Garcia Fernandez, J.M.: Probing secondary carbohydrate–protein interactions with highly dense cyclodextrin-centered heteroglycoclusters: the heterocluster effect. J. Am. Chem. Soc. 127, 7970–7971 (2005)CrossRefGoogle Scholar
  4. 4.
    Andre, S., Kaltner, H., Furuike, T., Nishimura, S.-I., Gabius, H.J.: Persubstituted cyclodextrin-based glycoclusters as inhibitors of protein-carbohydrate recognition using purified plant and mammalian lectins and wild-type and lectin-gene-transfected tumor cells as targets. Bioconjug. Chem. 15, 87–98 (2004)CrossRefGoogle Scholar
  5. 5.
    Attioui, F., Al-Omar, A., Leray, E., Parrot-Lopez, H., Finance, C., Bonaly, R.: Recognition ability and cytotoxicity of some oligosaccharidyl substituted β-cyclodextrins. Biol. Cell 82, 161–167 (1994)CrossRefGoogle Scholar
  6. 6.
    Sallas, F., Niikura, K., Nishimura, S.I.: A practical synthesis of amphiphilic cyclodextrins fully substituted with sugar residues on the primary face. Chem. Commun. 596–597 (2004)Google Scholar
  7. 7.
    Mourtzis, N., Paravatou, M., Mavridis, I.M., Roberts, M.L., Yannakopoulou, K.: Synthesis, characterisation, and remarkable biological properties of cyclodextrins bearing guanidinoalkylamino and aminoalkylamino groups on their primary side. Chem. Eur. J. 14, 4188–4200 (2008)CrossRefGoogle Scholar
  8. 8.
    Aggelidou, C., Mavridis, I.M., Yannakopoulou, K.: Binding of nucleotides and nucleosides to per(6-guanidino-6-deoxy)-cyclodextrins in solution. Eur. J. Org. Chem. 2299–2305 (2009)Google Scholar
  9. 9.
    Ermolenko, L., Sasaki, N.A.: Diastereoselective synthesis of all eight l-hexoses from l-ascorbic acid. J. Org. Chem. 71, 693–703 (2006)CrossRefGoogle Scholar
  10. 10.
    Hayes, W., Osborn, H.M.I., Osborne, S.D., Rastall, R.A., Romagnoli, B.: One-pot synthesis of multivalent arrays of mannose mono-and disaccharides. Tetrahedron 59, 7983–7996 (2003)CrossRefGoogle Scholar
  11. 11.
    Lindhorst, T.K., Kötter, S., Krallmann-Wenzel, U., Ehlers, S.: Trivalent α-d-mannoside clusters as inhibitors of type-1 fimbriae-mediated adhesion of Escherichia coli: structural variation and biotinylation. J. Chem. Soc. Perkin Trans. 1, 823–831 (2001)CrossRefGoogle Scholar
  12. 12.
    Ni, J., Singh, S., Wang, L.-X.: Synthesis of maleimide-activated carbohydrates as chemoselective tags for site-specific glycosylation of peptides and proteins. Bioconj. Chem. 14, 232–238 (2003)CrossRefGoogle Scholar
  13. 13.
    Roy, R., Kim, J.M.: Cu(II)-self-assembling bipyridyl-glycoclusters and dendrimers bearing the Tn-antigen cancer marker: syntheses and lectin binding properties. Tetrahedron 59, 3881–3893 (2003)CrossRefGoogle Scholar
  14. 14.
    Disney, M.D., Seeberger, P.H.: The use of carbohydrate microarrays to study carbohydrate-cell interactions and to detect pathogens. Chem. Biol. 11, 1701–1707 (2004)CrossRefGoogle Scholar
  15. 15.
    Izumi, M., Okumura, S., Yuasa, H., Hashimoto, H.: Mannose-BSA conjugates: comparison between commercially available linkers in reactivity and bioactivity. J. Carbohydr. Chem. 22, 317–329 (2003)CrossRefGoogle Scholar
  16. 16.
    Andersson, L.A., Dolphin, G.T., Kihlberg, J., Baltzer, L.: The effect of glycosylation on the structure of designed four-helix bundle motifs. J. Chem. Soc. Perkin Trans. 2, 459–464 (2000)Google Scholar
  17. 17.
    Andersson, L., Stenhagen, G., Baltzer, L.: The site-selective glycosylation of a designed helix-loop-helix polypeptide motif. J. Org. Chem. 63, 1366–1367 (1998)CrossRefGoogle Scholar
  18. 18.
    Ashton, P.R., Boyd, S.E., Brown, C.L., Nepogodiev, S.A., Meijer, E.W., Peerlings, H.W.I., Stoddart, J.F.: Synthesis of glycodendrimers by modification poly(propylene imine) dendrimers. Chem. Eur. J. 3, 974–984 (1997)CrossRefGoogle Scholar
  19. 19.
    Elofsson, M., Walse, B., Kihlberg, J.: Building blocks for glycopeptides synthesis: glycosylation of 3-mercaptopropionic acid and Fmoc amino acids with unprotected carboxyl groups. Tetrahedron Lett. 32, 7613–7616 (1991)CrossRefGoogle Scholar
  20. 20.
    Elofsson, M., Roy, S., Walse, B., Kihlberg, J.: Solid-phase synthesis and conformational studies of glycosylated derivatives of helper-T-cell immunogenic peptides from hen-egg lysozyme. Carbohydr. Res. 246, 89–103 (1993)CrossRefGoogle Scholar
  21. 21.
    Carpenter, C., Nepogodiev, S.A.: Synthesis of a αMan(1 → 3)αMan(1 → 2)αMan glycocluster presented on a β-cyclodextrin scaffold. Eur. J. Org. Chem. 3286–3296 (2005)Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Laboratory of Structural & Supramolecular Chemistry, Institute of Physical ChemistryNCSR “Demokritos”AthensGreece

Personalised recommendations