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  • Review Article
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Automated synthesis of oligosaccharides as a basis for drug discovery

Nature Reviews Drug Discovery volume 4, pages 751–763 (2005)Cite this article

Key Points

  • Solution-phase synthesis is a slow process due to the need for iterative coupling and deprotection steps, with purification at each step along the way. The first automated solid-phase oligosaccharide synthesizer based on a modified peptide synthesizer was introduced in 2001.

  • A number of highly successful drugs based on carbohydrates have been developed, such as acarbose, an α-glucosidase inhibitor, for the treatment of diabetes mellitus. Heparin is an even older carbohydrate-based drug that has been used since the 1940s. Much effort has been put in to preparing highly active synthetic heparin structures.

  • The presence of specific carbohydrates on the cell surface of particular types of cells opens up the possibility of creating vaccines. A hexasaccharide construct partly assembled by automated synthesis was shown to be immunogenic and to provide significant protection against malarial pathogenesis.

  • Special carbohydrate antigens, such as sialyl Lewis X and Globo-H, are known to be overexpressed on the surface of cancer cells. Patients immunized with synthetic carbohydrate-based vaccines produce antibodies that are reactive against malignant cells.

  • The presence of specific carbohydrates on the cell surface of particular cell populations presents the possibility of detecting these cells on the basis of their carbohydrate coat. This property is used in detecting even a small amount of bacteria with carbohydrate-functionalized fluorescent polymers.

Abstract

Carbohydrates present both potential and problems — their biological relevance has been recognized, but problems in procuring sugars rendered them a difficult class of compounds to handle in drug discovery efforts. The development of the first automated solid-phase oligosaccharide synthesizer and other methods to assemble defined oligosaccharides rapidly has fundamentally altered this situation. This review describes how quick access to oligosaccharides has not only contributed to biological, biochemical and biophysical investigations, but also to drug discovery. Particular focus will be placed on the development of carbohydrate-based vaccines, defined heparin oligosaccharides and aminoglycosides that have recently begun to affect drug discovery.

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Figure 1
Figure 2: The first automated oligosaccharide synthesizer.
Figure 3: Automated assembly of fully protected Lewis X-Lewis Y nonasaccharide 1.
Figure 4
Figure 5: Carbohydrate-based parasite vaccine candidates.
Figure 6
Figure 7: Exploiting multivalency to detect bacteria.
Figure 8: Detecting bacteria using fluorescent polymers.

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References

  1. Hunkapiller, T., Kaiser, R. J., Koop, B. F. & Hood, L. Large-scale and automated DNA sequence determination. Science 354, 59–67 (1991).

    Article  Google Scholar 

  2. Caruthers, M. H. Gene synthesis machines: DNA chemistry and its uses. Science 230, 281–285 (1985). The essentials for the synthetic assembly of genes are presented.

    Article  CAS  Google Scholar 

  3. Caruthers, M. H. Chemical synthesis of DNA and DNA analogs. Acc. Chem. Res. 24, 278–284 (1991).

    Article  CAS  Google Scholar 

  4. Atherton, E. & Sheppard, R. C. Solid-Phase Peptide Synthesis: A Practical Approach (Oxford Univ. Press, Oxford, 1989).

    Google Scholar 

  5. Sears, P. & Wong, C. -H. Toward automated synthesis of oligosaccharides and glycoproteins. Science 291, 2344–2350 (2001).

    Article  CAS  Google Scholar 

  6. Wong, C. -H. Enzymic and chemo-enzymic syntheses of carbohydrates. Pure Appl. Chem. 67, 1609–1616 (1995).

    Article  CAS  Google Scholar 

  7. Plante, O. J., Palmacci, E. R. & Seeberger, P. H. Automated solid-phase synthesis of oligosaccharides. Science 291, 1523–1527 (2001). The first automated solid-phase oligosaccharide synthesizer is presented. Linear and branched structures up to dodecasaccharides are prepared.

    Article  CAS  Google Scholar 

  8. Seeberger, P. H. Automated carbohydrate synthesis to drive chemical glycomics. Chem. Commun. 1115–1121 (2003).

  9. Laine, R. A. A calculation of all possible oligosaccharide isomers both branched and linear yields 1.05 × 1012 structures for a reducing hexasaccharide: the isomer barrier to development of single-method saccharide sequencing or synthesis systems. Glycobiology 4, 759–767 (1994).

    Article  CAS  Google Scholar 

  10. Schmidt, R. R., Castro-Palomino, J. C. & Retz, O. New aspects of glycoside bond formation. Pure Appl. Chem. 71, 729–744 (1999).

    Article  CAS  Google Scholar 

  11. Koeller, K. & Wong, C. -H. Synthesis of complex carbohydrates and glycoconjugates: enzyme-based and programmable one-pot strategies. Chem. Rev. 100, 4465–4493 (2000).

    Article  CAS  Google Scholar 

  12. Wong, C. -H., Halcomb, R. L., Ichikawa, Y. & Kajimoto, T. Enzymes in organic synthesis: application to the problems of carbohydrate recognition. Part 1. Angew. Chem. Int. Ed. Engl. 34, 412–432 (1995).

    Article  CAS  Google Scholar 

  13. Wong, C. -H., Halcomb, R. L., Ichikawa, Y. & Kajimoto, T. Enzymes in organic synthesis: application to the problems of carbohydrate recognition. Part 2. Angew. Chem. Int. Ed. Engl. 34, 521–546 (1995).

    Article  CAS  Google Scholar 

  14. Chen, X. et al. Sugar nucleotide regeneration beads (superbeads): a versatile tool for the practical synthesis of oligosaccharides. J. Am. Chem. Soc. 123, 2081–2082 (2001).

    Article  CAS  Google Scholar 

  15. Delorme, E. et al. Role of glycosylation on the secretion and biological activity of erythropoietin. Biochemistry 31, 9871–9876 (1992).

    Article  CAS  Google Scholar 

  16. Jiang, J., Biggins, J. B. & Thorson, J. S. A general enzymatic method for the synthesis of natural and 'unnatural' UDP- and TDP-nucleotide sugars. J. Am. Chem. Soc. 122, 6803–6804 (2000).

    Article  CAS  Google Scholar 

  17. Ye, X. -S. & Wong, C. -H. Anomeric reactivity-based one-pot oligosaccharide synthesis: a rapid route to oligosaccharide libraries. J. Org. Chem. 65, 2410–2431 (2000).

    Article  CAS  Google Scholar 

  18. Douglas, N. L., Ley, S. V., Lucking, U. & Warriner, S. L. Tuning glycoside reactivity: new tool for efficient oligosaccharide synthesis. J. Chem. Soc., Perkin Trans. 1 51–65 (1998).

  19. Lassaletta, J. & Schmidt, R. R. Glycosyl imidates. Part 75. Synthesis of the hexasaccharide moiety of globo H (human breast cancer) antigen. Liebigs Ann. 1417–1423 (1996). The first total synthesis of Globo-H hexasaccharide is reported.

  20. Park, T. K. et al. Total synthesis and proof of structure of a human breast tumor (Globo-H) antigen. J. Am. Chem. Soc. 118, 11488–11500 (1996).

    Article  CAS  Google Scholar 

  21. Bosse, F., Marcaurelle, L. A. & Seeberger, P. H. Linear synthesis of tumor-associated carbohydrate antigens Globo-H, SSEA-3, and Gb3. J. Org. Chem. 67, 6659–6670 (2002).

    Article  CAS  Google Scholar 

  22. Takahashi, T., Adachi, M., Matsuda, A. & Doi, T. Combinatorial synthesis of trisaccharides via solution-phase one-pot glycosylation. Tetrahedron Lett. 41, 2599–2603 (2000).

    Article  CAS  Google Scholar 

  23. Frechet, J. M. in Polymer-supported Reactions in Organic Synthesis (eds Hodge, P. & Sherrington, D. C.) 407–434 (Wiley, Chichester, 1980). Provides a review of solid-phase oligosaccharide synthesis before 1980.

    Google Scholar 

  24. Seeberger, P. H. & Haase, W. -C. Solid-phase oligosaccharide synthesis and combinatorial carbohydrate libraries. Chem. Rev. 100, 4349–4393 (2000). A recent review of solid-phase oligosaccharide assembly.

    Article  CAS  Google Scholar 

  25. Seeberger, P. H. (ed.) Solid Support Oligosaccharide Synthesis and Combinatorial Carbohydrate Libraries (Wiley-Interscience, Chichester, 2001).

    Book  Google Scholar 

  26. Plante, O. J., Andrade, R. B. & Seeberger, P. H. Synthesis and use of glycosyl phosphates as glycosyl donors. Org. Lett. 1, 211–214 (1999).

    Article  CAS  Google Scholar 

  27. Schmidt, R. R. & Kinzy, W. Anomeric-oxygen activation for glycoside synthesis: the trichloroacetimidate method. Adv. Carbohydr. Chem. Biochem. 50, 21–123 (1994).

    Article  CAS  Google Scholar 

  28. Love, K. R. & Seeberger, P. H. Automated solid-phase synthesis of protected tumor-associated antigen and blood group determinant oligosaccharides. Angew. Chem. Int. Ed. Engl. 43, 602–605 (2004). The synthesis of Lewis oligosaccharides was successfully performed on the automated oligosaccharide synthesizer starting from five different monomeric building blocks.

    Article  CAS  Google Scholar 

  29. Capdeville, R., Buchdunger, E., Zimmermann, J. & Matter, A. Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nature Rev. Drug Discov. 1, 493–502 (2002).

    Article  CAS  Google Scholar 

  30. Manson, M. M. et al. Modulation of signal-transduction pathways by chemopreventive agents. Biochem. Soc. Trans. 28, 7–12 (2000).

    Article  CAS  Google Scholar 

  31. Wilson, W. D., Ratmeyer, L., Zhao, M., Strekowski, L. & Boykin, D. The search for structure-specific nucleic acid-interactive drugs: effects of compound structure on RNA versus DNA interaction strength. Biochemistry 32, 4098–4104 (1993).

    Article  CAS  Google Scholar 

  32. Geijtenbeek, T. B. H. et al. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune response. Cell 100, 575–585 (2000).

    Article  CAS  Google Scholar 

  33. Kansas, G. S. Selectins and their ligands: current concepts and controversies. Blood 88, 3259–3287 (1996).

    CAS  PubMed  Google Scholar 

  34. Barnes-Seemann, D., Park, S. B., Koehler, A. N. & Schreiber, S. L. Expanding the functional group compatibility of small molecule microarrays: discovery of novel calmodulin ligands. Angew. Chem. Int. Ed. Engl. 42, 2478–2481 (2003).

    Article  Google Scholar 

  35. Fukui, S., Feizi, T., Galustian, C., Lawson, A. M. & Chai, W. Oligosaccharide microarrays for high throughput detection and specificity assignments of carbohydrate-protein interactions. Nature Biotechnol. 20, 1011–1017 (2002).

    Article  CAS  Google Scholar 

  36. Hergenrother, P. J., Depew, K. M. & Schreiber, S. L. Small molecule microarrays: covalent attachment and screening of alcohol-containing small molecules on glass slides. J. Am. Chem. Soc. 122, 7849–7850 (2000).

    Article  CAS  Google Scholar 

  37. Walsh, C. Molecular mechanisms that confer antibacterial drug resistance. Nature 406, 775–781 (2000).

    Article  CAS  Google Scholar 

  38. Llano-Sotelo, B., Azucena, E. F. Jr., Kotra, L. P., Mobashery, S. & Chow, C. S. Aminoglycosides modified by resistance enzymes display diminished binding to the bacterial ribosomal aminoacyl-tRNA site. Chem. Biol. 9, 455–463 (2002).

    Article  CAS  Google Scholar 

  39. Disney, M. D., Magnet, S., Blanchard, J. S. & Seeberger, P. H. Aminoglycoside microarrays to study antibiotic resistance. Angew. Chem. Int. Ed. Engl. 43, 1591–1594 (2004).

    Article  CAS  Google Scholar 

  40. Disney, M. D. & Seeberger, P. H. Aminoglycoside microarrays to explore interactions of antibiotics with RNAs and proteins. Chem. Eur. J. 10, 3308–3314 (2004).

    Article  CAS  Google Scholar 

  41. Truscheit, E. et al. Chemistry and biochemistry of microbial α-glucosidase inhibitors. Angew. Chem. Int. Ed. Engl. 20, 744–761 (1981).

    Article  Google Scholar 

  42. Capila, I. & Linhardt, R. J. Heparin–protein interactions. Angew. Chem. Int. Ed. Engl. 41, 390–412 (2002).

    Article  CAS  Google Scholar 

  43. Tabeur, C. et al. Oligosaccharides corresponding to the regular sequence of heparin: chemical synthesis and interaction with FGF-2. Bioorg. Med. Chem. 7, 2003–2012 (1999).

    Article  CAS  Google Scholar 

  44. Petitou, M., Casu, B. & Lindahl, U. 1976–1983, a critical period in the history of heparin: the discovery of the antithrombin binding site. Biochimie 85, 83–89 (2003).

    Article  CAS  Google Scholar 

  45. Petitou, M. & van Boeckel, C. A. A. A synthetic antithrombin III binding pentasaccharide is now a drug! What comes next? Angew. Chem. Int. Ed. Engl. 43, 3118–3133 (2004). An excellent account of the state-of-the-art in heparin drug research.

    Article  CAS  Google Scholar 

  46. Lee, J. -C., Lu, X. -A., Kulkarni, S. S., Wen, Y. -S. & Hung, S. -C. Synthesis of heparin oligosaccharides. J. Am. Chem. Soc. 126, 476–477 (2004).

    Article  CAS  Google Scholar 

  47. Goldblatt, D. Recent developments in bacterial conjugate vaccines. J. Med. Microbiol. 47, 563–567 (1998).

    Article  CAS  Google Scholar 

  48. Talbo, G. & Mann, M. Aspects of the sequencing of carbohydrates and oligonucleotides by matrix-assisted laser desorption/ionization post-source decay. Rap. Commun. Mass Spectr. 10, 100–103 (1996).

    Article  CAS  Google Scholar 

  49. De Waard, P., Boelens, R., Vuister, G. W. & Vliegenthart, J. F. G. Structural studies by proton/carbon-13 two-dimensional and three-dimensional HMQC-NOE at natural abundance on complex carbohydrates. J. Am. Chem. Soc. 112, 3232–3234 (1990).

    Article  CAS  Google Scholar 

  50. Sood, R. K., Fattom, A., Pavliak, V. & Naso, R. B. Capsular polysaccharide–protein conjugate vaccines. Drug Discov. Today 1, 381–387 (1996).

    Article  CAS  Google Scholar 

  51. Tachado, S. D. et al. Signal transduction in macrophages by glycosylphosphatidylinositols of Plasmodium, Trypanosoma, and Leishmania: activation of protein tyrosine kinases and protein kinase C by inositolglycan and diacylglycerol moieties. PNAS 94, 4022–4027 (1997).

    Article  CAS  Google Scholar 

  52. World Health Organization World Malaria situation 1990. World Health Stat. Q. 45, 257–266 (1992).

  53. Berhe, S., Schofield, L., Schwarz, R. T. & Gerold, P. Conservation of structure among glycosylphosphatidylinositol toxins from different geographic isolates of Plasmodium falciparum. Mol. Biochem. Parasitol. 103, 273–278 (1999).

    Article  CAS  Google Scholar 

  54. Hewitt, M. C., Snyder, D. A. & Seeberger, P. H. Rapid synthesis of a glycosylphosphatidylinositol-based malaria vaccine using automated solid-phase oligosaccharide synthesis. J. Am. Chem. Soc. 124, 13434–13436 (2002).

    Article  CAS  Google Scholar 

  55. Schofield, L., Hewitt, M. C., Evans, K., Siomos, M. -A. & Seeberger, P. H. Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria. Nature 418, 785–789 (2002). This study identified a novel malaria vaccine candidate.

    Article  CAS  Google Scholar 

  56. Mitchell, G. F. & Handman, E. The glycoconjugate derived from a Leishmania lipopolysaccharide confers parasite survival in macrophages. Parasite Immun. 8, 255–263 (1986).

    Article  CAS  Google Scholar 

  57. Herwaldt, B. L. Leishmaniasis. Lancet 354, 1191–1199 (1999).

    Article  CAS  Google Scholar 

  58. Turco, S. J. & Descoteaux, A. The lipophosphoglycan of Leishmania parasites. Annu. Rev. Microbiol. 46, 65–94 (1992).

    Article  CAS  Google Scholar 

  59. Hewitt, M. C. & Seeberger, P. H. Solution and solid-support synthesis of a potential leishmaniasis carbohydrate vaccine. J. Org. Chem. 66, 4233–4243 (2001).

    Article  CAS  Google Scholar 

  60. Hewitt, M. C. & Seeberger, P. H. Automated solid-phase synthesis of a branched Leishmania cap tetrasaccharide. Org. Lett. 3, 3699–3702 (2001).

    Article  CAS  Google Scholar 

  61. Kannagi, R. et al. New globoseries glycosphingolipids in human teratocarcinoma reactive with the monoclonal antibody directed to a developmentally regulated antigen, stage-specific embryonic antigen 3. J. Biol. Chem. 258, 8934–8942 (1983).

    CAS  PubMed  Google Scholar 

  62. Danishefsky, S. J. & Allen, J. R. From the laboratory to the clinic: a retrospective on fully synthetic carbohydrate-based anticancer vaccines. Angew. Chem. Int. Ed. Engl. 39, 836–863 (2000).

    Article  CAS  Google Scholar 

  63. Keding, S. J. & Danishefsky, S. J. in Carbohydrate-Based Drug Discovery Vol. 1 (ed. Wong, C.-H.) 381–406 (Wiley-VCH, Weinheim, 2003).

    Google Scholar 

  64. Menard, S., Tagliabue, E., Canevari, S., Fossati, G. & Colnaghi, M. I. Generation of monoclonal antibodies reacting with normal and cancer cells of human breast. Cancer Res. 43, 1295–1300 (1983).

    CAS  PubMed  Google Scholar 

  65. Livingston, P. O. Augmenting the immunogenicity of carbohydrate tumor antigens. Cancer Biol. 6, 357–366 (1995).

    Article  CAS  Google Scholar 

  66. Zhang, S. et al. Selection of tumor antigens as targets for immune attack using immunohistochemistry: I. Focus on gangliosides. Int. J. Cancer 3, 42–49 (1997).

    Article  Google Scholar 

  67. Kitov, P. I. & Bundle, D. R. Thermodynamic models of the multivalency effect. Carbohydrate-Based Drug Discovery 2, 541–574 (2003).

    CAS  Google Scholar 

  68. Karlsson, K. A. Bacterium-host protein carbohydrate interactions and pathogenicity. Biochem. Soc. Trans. 27, 471–474 (1999).

    Article  CAS  Google Scholar 

  69. Karlsson, K. A. Pathogen-host protein–carbohydrate interactions as the basis of important infections. Adv. Exp. Med. Biol. 491, 431–443 (2001).

    Article  CAS  Google Scholar 

  70. Mammen, M., Choi, S. -K. & Whitesides, G. M. Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors. Angew. Chem. Int. Ed. Engl. 37, 2745–2794 (1998).

    Article  Google Scholar 

  71. Disney, M. D., Zheng, J., Swager, T. M. & Seeberger, P. H. Detection of bacteria with carbohydrate-functionalized fluorescent polymer. J. Am. Chem. Soc. 126, 13343–13346 (2004).

    Article  CAS  Google Scholar 

  72. 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).

    Article  CAS  Google Scholar 

  73. Garegg, P. J. Thioglycosides as glycosyl donors in oligosaccharide synthesis. Adv. Carbohydr. Chem. Biochem. 52, 179–205 (1997).

    Article  CAS  Google Scholar 

  74. Kahne, D., Walker, S., Cheng, Y. & van Engen, D. Glycosylation of unreactive substrates. J. Am. Chem. Soc. 111, 6881–6882 (1989).

    Article  CAS  Google Scholar 

  75. Koenigs, W. & Knorr, E. Derivatives of grape sugar and galactose. Chem. Ber. 34, 957–981 (1901).

    Article  Google Scholar 

  76. Mukaiyama, T., Murai, Y. & Shoda, S. An efficient method for glucosylation of hydroxy compounds using glucopyranosyl fluoride. Chem. Lett. 431–432 (1981).

  77. Kondo, H. et al. Glycosyl phosphites as glycosylation reagents: scope and mechanism. J. Org. Chem. 59, 864–877 (1994).

    Article  CAS  Google Scholar 

  78. Plante, O. J., Palmacci, E. R., Andrade, R. B. & Seeberger, P. H. Oligosaccharide synthesis with glycosyl phosphate and dithiophosphate triesters as glycosylating agents. J. Am. Chem. Soc. 123, 9545–9554 (2001).

    Article  CAS  Google Scholar 

  79. Fraser-Reid, B., Konradsson, P., Mootoo, D. R. & Udodong, U. Direct elaboration of pent-4-enyl glycosides into disaccharides. J. Chem. Soc. Chem. Commun. 823–825 (1988).

  80. Seeberger, P. H., Bilodeau, M. T. & Danishefsky, S. Synthesis of biologically important oligosaccharides and other glycoconjugates by the glycal assembly method. J. Aldrichimica Acta 30, 75–92 (1997).

    CAS  Google Scholar 

  81. de Paz, J. -L. et al. The activation of fibroblast growth factors by heparin: synthesis, structure, and biological activity of heparin-like oligosaccharides. ChemBioChem 2, 673–685 (2001).

    Article  CAS  Google Scholar 

  82. Prabhu, A., Venot, A. & Boons, G. -J. New set of orthogonal protecting groups for the modular synthesis of heparan sulfate fragments. Org. Lett. 5, 4975–4978 (2003).

    Article  CAS  Google Scholar 

  83. Orgueira, H. A. et al. Modular synthesis of heparin oligosaccharides. Chem. Eur. J. 9, 140–169 (2003). A highly flexible modular approach for the construction of heparin-like structures is presented.

    Article  CAS  Google Scholar 

  84. Shukla, D. et al. A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell 99, 13–22 (1999).

    Article  CAS  Google Scholar 

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Acknowledgements

D.B.W. thanks the Alexander von Humboldt Foundation (AvH) for a Feodor Lynen Research Fellowship and the Deutsche Forschungsgemeinschaft (DFG) for a Emmy Noether Fellowship. P.H.S. thanks the Swiss Federal Institute of Technology (ETH) and the Swiss National Science Foundation for financial support.

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  1. Laboratory for Organic Chemistry, Swiss Federal Institute of Technology (ETH) Zürich, HCI F315, Wolfgang-Pauli-Str. 10, Zürich, 8093, Switzerland

    Peter H. Seeberger & Daniel B. Werz

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Correspondence to Peter H. Seeberger.

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P.H.S. holds stock in Ancora Pharmaceuticals, a company that utilizes automated oligosaccharide synthesis in drug discovery.

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Glossary

GENOMICS AND PROTEOMICS

All aspects dealing with the biology of nucleic acids and proteins. Analogous, for all aspects dealing with glycobiology the term 'glycomics' was introduced.

POLYMERASE CHAIN REACTION (PCR)

The purpose of this enzymatic reaction is to make a huge number of copies of a gene. This is necessary to have enough starting template for sequencing.

PROTECTING GROUP

A chemical moiety that is introduced to prevent a reaction at a certain position. Protecting groups can be permanent or temporary. The former remain during the complete synthesis in the molecule, whereas the latter protect the functional group only during some steps. Protecting groups should also be removable in an easy fashion.

ONE-POT METHOD

Sequence of reactions carried out in the same reaction vessel without purifying intermediate compounds.

SOLID-PHASE CHEMISTRY

In solid-phase synthesis, the compounds being synthesized are attached (usually by a linker moiety) to an insoluble polymeric material (usually beads or resin), allowing the reaction products to be readily separated (for example, by filtration or centrifugation) from excess reagent, soluble reaction by-products and solvents.

ANTIGEN

Antigens are macromolecules that elicit an immune response in the body. Antigens can be proteins, conjugates of lipids with proteins (lipoproteins) or polysaccharides (glycolipids).

SELECTINS

A family of carbohydrate-binding proteins (lectins) expressed on activated platelets (P-selectin) and endothelial cells (P- and E-selectin).

EPITOPE

A part of an antigen to which an antibody binds. Also called an antigenic determinant.

MICROARRAY

A chip, prepared by attachment of biopolymers to a surface in a spatially discrete pattern. Microarrays have enabled a low-cost and high-throughput methodology to screen interactions of molecules.

α-GLUCOSIDASE

Carbohydrate-splitting enzymes that catalyse the hydrolysis of α-glucosidic linkages in oligo- and polysaccharides.

KEYHOLE LIMPET HAEMOCYANIN

A high-molecular-mass polymeric glycoprotein derived from the haemolymph of the giant sea mollusk Megathura crenulata and frequently used as a highly immunogenic carrier for carbohydrate antigens.

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Seeberger, P., Werz, D. Automated synthesis of oligosaccharides as a basis for drug discovery. Nat Rev Drug Discov 4, 751–763 (2005). https://doi.org/10.1038/nrd1823

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