Skip to main content

Combinatorial Carbohydrate Chemistry

  • Chapter
Glycoimmunology 2

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 435))

Abstract

Modern organic/medicinal chemistry is undergoing a “cultural revolution” in the way new drugs are discovered and developed. Instead of discrete synthess and biological screening of individual compounds, which often takes years to identify and optimize leads, the currently developing technology called “combinatorial chemistry” can rapidly provide large numbers of chemicals (libraries) in a short time. In conjunction with these new synthetic methods, high-throughput screening (HTS) can rapidly screen the libraries produced, and in so doing, can provide information for optimizing lead compounds. This is going to lighten the increasing burden traditional drug development places on the pharmaceutical industry. For this reason, the generation of chemical libraries through combinatorial chemistry, including parallel synthesis, is making explosive progress both in academic and industrial areas in the last two years, especially for creating peptide, nucleotide and small molecule libraries. A number of excellent reviews1 on this field have appeared.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. M.A. Gallop, R.W. Barrett, W.J. Dower, S.P.A. Fodor, and E.M. Gordon, Application of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries, J. Med. Chem. 37:1233 (1994). 2. Combinatorial organic synthesis, library screening strategies and future directions, 37:1385 (1994).

    Article  PubMed  CAS  Google Scholar 

  2. L.A. Thompson and J.A. Ellman. Synthesis ands applications of small molecular libraries. Chem. Rev. 96:555(1996).

    Article  PubMed  CAS  Google Scholar 

  3. P.H.H. Hermkens, H.C.J. Ottenheijm, and D. Rees, Solid phase organic reactions: a review of the recent literature, Tetrahedron 52:4527 (1996)

    Article  CAS  Google Scholar 

  4. F. Balkenhohl, C. Bussche-Hunnefeld, A. Lansky, and C. Zechel, Combinatorial synthesis of small organic molecules, Angew. Chem. Int. Ed. Engl. 35:2288 (1996).

    Article  CAS  Google Scholar 

  5. A recent general review about glycosylation: K. Toshima, and K. Tatsuta, Recent progress in O-glycosylation methods and its application to natural products synthesis, Chem. Rev. 93:1503 (1993).

    Article  CAS  Google Scholar 

  6. See a recent review: J.C. Mc Auliffe, and O. Hindsgaul, Carbohydrate drugs—an ongoing challenge, Chemistry and Industry 170 (1997).

    Google Scholar 

  7. O. Kanie, F. Bafresi, Y. Ding, J. Labbe, A. Otter, L. S. Forsberg, B. Ernst, and O. Hindsgaul. A strategy of “random glycosylation” for the production of oligosaccharide libraries, Angew. Chem. Int. Ed. Engl. 34:2720 (1995).

    Article  CAS  Google Scholar 

  8. Y. Ding, J. Labbe, O. Kanie, and O. Hindsgaul, Towards oligosaccharide libraries: a study of the random galactosylation of unprotected N-acetylglucosamine, Bioorg. Biomed. Chem. 4:683 (1996).

    CAS  Google Scholar 

  9. G.J. Boons, B. Heskamp, and F. Hout, Vinyl glycosides in oligosaccharide synthesis: a strategy for the preparation of trisaccharide libraries based on latent-active glycosylation, Angew. Chem. Int. Ed, Engl. 35:2845 (1996).

    Article  CAS  Google Scholar 

  10. Z.G. Wang, S. Douglas and J.J. Krepinsky, Polymer-supported synthesis of oligosaccharides: using dibutylboron triflate to promote glycosylation with glycosyl trichloro-acetimidates, Tetrahedron Lett. 37:6985 (1996).

    Article  CAS  Google Scholar 

  11. J.J. Krepinsky, 212th Amercian Chemical Society National Meeting at Orlando, August 25–29, Division of Organic Chemistry, 003 (1996). Previous works on soluble-phase polymer-supported synthesis See: S. Douglas, D.M. Whitfiled, and J.J. Krepinsky, Polymer-supported synthesis of oligosaccharides using a novel versatile linker for the synthesis of D-mannopentaose, a structural unit of D-Mannans of pathogenic yeasts, J. Am. Chem. Soc. 117:2116 (1995).

    Google Scholar 

  12. R. Liang, L. Yan, J. Loebach, M. Ge, Y. Uozumi, K. Sekanina, N. Horan, J. Gildersleeve, C. Thompsom, A. Smith, K. Biswas, W. C. Still, and D. Kahne, Parallel synthesis and screening of a solid phase carbohydrate library, Science. 274:1520 (1996).

    Article  PubMed  CAS  Google Scholar 

  13. C.C. Lenzof, The use of insoluble polymer supports in general organic synthesis, Acc. Chem. Res.. 11:327 (1978).

    Article  Google Scholar 

  14. For a review of solid-phase synthesis of oligosaccharides up to 1980, see J. M. Frechet, In polymer-supported synthesis of oligosaccharides, Hodge, P., Sherrington, D.C., eds., Wiley: Chichester, 407 (1980) and reference cited there. (a) U. Zehavi, and A. Patchornik, Oligosaccharide synthesis on a light-sensitive solid support. the polymer and synthesis of isomaltose( 6-O-a-D-glucopyranosyl-D-glucose). J. Am. Chem. Soc. 95: 5673 (1973) (b) J. M. Frechet, and C. Schuerch, Solid-phase synthesis of oligosaccharides. Preparation of the solid support. poly[p-(l-propen-3-ol-l-yl) styrene], J. Am. Chem. Soc. 93: 492 (1971).

    Google Scholar 

  15. G. H. Veeneman, S. Notermans, R. M. Liskamp, G. A. van der Marel, and J. H. van Boom, Solid-phase synthesis of a natually occuring β-(1→5)-linked D-galactofuranosyl heptamer containing the artificial linkage arm L-homoserine, Tetrahedron Lettt. 28: 6695 (1987)

    Article  CAS  Google Scholar 

  16. J. Rademann, and R. R. Schmidt, A new method of the solid-phase synthesis of oligosaccharides, Tetrahedron Lett. 37:3989 (1996).

    Article  CAS  Google Scholar 

  17. J. A. Hunt, and W. R. Roush, Solid-phase synthesis of 6-deoxyoligosaccharides, J. Am. Chem. Soc. 118:9998 (1996).

    Article  CAS  Google Scholar 

  18. K.C. Nicolaou, N. Winssinger, J. Pastor, and F. DeRoose, A general and highly efficient solid phase synthesis of oligosaccharides: total synthesis of a heptasaccharide phytoalexin elicitor (HPE), J. Am. Chem. Soc. 119:449 (1997).

    Article  CAS  Google Scholar 

  19. L. Yan, C.M. Taylor, R. Goodnow, and D. Kahne, Glycosylation on the Merrifield resin using anomeric sulfoxides, J. Am. Chem. Soc. 116:6953 (1994).

    Article  CAS  Google Scholar 

  20. S. Nilsson, M. Bengtsson, and T. Norberg, Solid-phase synthesis of a fragment of the capsular polysaccharide of haemophilus influenzae type B using H-phosphonate intermediates, J. Carbohydrate chemistry 11:265 (1992).

    Article  CAS  Google Scholar 

  21. M. Schuster, P. Wang, J.C. Paulson, and C.H. Wong, Solid-phase chemical-enzymatic synthesis of glycopeptides and oligosaccharide, J. Am. Chem. Soc. 116:1135 (1994).

    Article  CAS  Google Scholar 

  22. Y. Ito, O. Kanie, and T. Ogawa, Orthogonal glycosylation strategy for rapid assembly of oligosaccharides on a polymer support, Angew. Chem. Int. Ed. Engl. 35:2510 (1996).

    Article  CAS  Google Scholar 

  23. J. Y. Roberge, X. Beebe, and S.J. Danishefsky, A strategy for a convergent synthesis of N-linked glycopeptides on a solid support, Science 269:202 (1995).

    Article  PubMed  CAS  Google Scholar 

  24. S.J. Danishefky, K.F. McClure, J.T. Randolph, and R.B. Ruggeri, A strategy for the solidphase synthesis of oligosaccharides, Science 260:1307 (1993).

    Article  Google Scholar 

  25. J.T. Randolph, K.F. McClure, and S.J. Danishefky, Major simplifications in oligosaccharide syntheses arising from a solid-phase based method: an application to the synthesis of the Lewis b antigen, J. Am. Chem. Soc. 117:5712 (1995).

    Article  CAS  Google Scholar 

  26. U.J. Nilsson, and O. Hindsgaul, Combinatorial michael additions and reductive aminations towards carbohydrate libraries designed to inhibit galactose-binding protein. XVIII International Carbohydrate Symposium. Milano, Italy, Abstract P 212 (1996).

    Google Scholar 

  27. H.P. Wessel, C.M. Mitchell, CM. Lobato, and G. Schmid, Saccharide-peptide hybrids as novel oligosaccharide mimetics. Angew. Chem. Int. Ed. Engl. 34:2712 (1995).

    Article  CAS  Google Scholar 

  28. E.G. von Roedern, and A. Kessler, A sugar amino acid as a novel peptidomimetic, Angew. Chem. Int. Ed. Engl.. 33:687 (1994).

    Article  Google Scholar 

  29. J.P. McDevitt, and P.T. Lansbury, Glycosamino acid: new building blocks for combinatorial synthesis, J. Am. Chem. Soc. 118:3818 (1996).

    Article  CAS  Google Scholar 

  30. M.H.D. Postema, Recent development in the synthesis of C-glycosides, Tetrahedron 48:8545 (1992).

    Article  CAS  Google Scholar 

  31. I. Ugi, From isocyanides via four-component condensations to antibiotic synthesis, Angew. Chem. Int. Ed. Engl. 21:810 (1982).

    Article  Google Scholar 

  32. D.P. Sutherlin, T.M. Stark, R. Hughes, and R.W. Armstrong, Generation of C-glycoside peptide ligands for cell surface carbohydrate receptors using a four-component condensation on solid support, J. Org. Chem. 61:8350 (1996).

    Article  PubMed  CAS  Google Scholar 

  33. W.K. Park, M. Auer, H. Jaksche, and C.H. Wong, Rapid combinatorial synthesis of aminoglycoside antibiotic mimetics: use of a polyethylene glycol-linked amine and a neamine-derived aldehyde in multiple component condensation as a strategy for the discovery of new inhibitors of the HIV RNA rev responsive element, J. Am. Chem. Soc. 118:10150 (1996).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

Wang, ZG., Hindsgaul, O. (1998). Combinatorial Carbohydrate Chemistry. In: Axford, J.S. (eds) Glycoimmunology 2. Advances in Experimental Medicine and Biology, vol 435. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5383-0_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5383-0_21

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7457-2

  • Online ISBN: 978-1-4615-5383-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics