The chemical synthesis of oligosaccharides normally relies on the coupling of separate existing monosaccharide parts through the formation of the glycosidic bond. However, this method often suffers from laborious protection strategies and difficulties with controlling the stereochemistry and position of the glycosidic linkage.
Jatta A. Himanen and Petri M. Pihko University of Jyväskylä, Finland, present a new strategy for the synthesis of di- and trisaccharides based on a de novo saccharide linchpin construction. In this strategy, functionalized monosaccharide building blocks already incorporating the glycosidic linkages are welded together using a Cr-catalyzed hetero-Diels–Alder (HDA) reaction to generate a new monosaccharide unit between them. The highest yields and selectivities in the HDA reaction were obtained by using chiral Schiff base chromium complexes.
For the synthesis of trisaccharide products, acetyl-protected glucose or galactose-derived dienes were fused with monosaccharide-derived aldehydes using chromium catalysts for the HDA reaction. The desired trisaccharide products were obtained in moderate to good yields with excellent stereoselectivity.
The central pyranulose-ring generated in the process possessed an L-cisenulose configuration according to NMR spectroscopy and modeling studies.
Article Views: 3003
1. Armstrong, G. D., E. Fodor, and R. Vanmaele. 1991. Investigation of Shiga-like toxin binding to chemically synthesized oligosaccharide sequences. J. Infect. Dis.164:1160-1167. [PubMed]
2. Brinkmann, N., M. Malissard, M. Ramuz, U. Romer, T. Schumacher, E. G. Berger, L. Elling, C. Wandrey, and A. Liese. 2001. Chemo-enzymatic synthesis of the galili epitope Galα(1-3)Galβ(1-4)GlcNAc on a homogeneously soluble PEG polymer by a multi-enzyme system. Bioorg. Med. Chem. Lett.11:2503-2506. [PubMed]
3. Bulter, T., and L. Elling. 1999. Enzymatic synthesis of nucleotide sugars. Glycoconjugate J.16:147-159. [PubMed]
4. Calderwood, S. B., F. Auclair, A. Donahue-Rolfe, G. T. Keusch, and J. J. Mekalanos. 1987. Nucleotide sequence of the Shiga-like toxin genes of Escherichia coli. Proc. Natl. Acad. Sci. USA84:4364-4368. [PMC free article][PubMed]
5. Chen, X., P. Kowal, and P. G. Wang. 2000. Large-scale enzymatic synthesis of oligosaccharides. Curr. Opin. Drug Disc. Dev.3:756-763. [PubMed]
6. Chen, X., Z. Liu, J. Wang, and P. G. Wang. 2000. Changing the donor cofactor of bovine α1, 3-galactosyltransferase by fusion with UDP-galactose 4-epimerase. More efficient biocatalysis for synthesis of α-Gal epitopes. J. Biol. Chem.275:31594-31600. [PubMed]
7. Chen, X., J. Zhang, P. Kowal, Z. Liu, P. R. Andreana, Y. Lu, and P. G. Wang. 2001. Transferring a biosynthetic cycle into a productive Escherichia coli strain: large-scale synthesis of galactosides. J. Am. Chem. Soc.123:8866-8867. [PubMed]
8. Crout, D. H. G., and G. Vic. 1998. Glycosidases and glycosyl transferases in glycoside and oligosaccharide synthesis. Curr. Opin. Chem. Biol.2:98-111. [PubMed]
9. Curatti, L., A. C. Porchia, L. Herrera-Estrella, and G. L. Salerno. 2000. A prokaryotic sucrose synthase gene (susA) isolated from a filamentous nitrogen-fixing cyanobacterium encodes a protein similar to those of plants. Planta211:729-735. [PubMed]
10. Endo, T., S. Koizumi, K. Tabata, and A. Ozaki. 2000. Cloning and expression of β1,4-galactosyltransferase gene from Helicobacter pylori. Glycobiology10:809-813. [PubMed]
11. Endo, T., S. Koizumi, K. Tabata, and A. Ozaki. 2000. Large-scale production of CMP-NeuAc and sialylated oligosaccharides through bacterial coupling. Appl. Microbiol. Biotechnol.53:257-261. [PubMed]
12. Endo, T., S. Koizumi, K. Tabata, S. Kakita, and A. Ozaki. 2001. Large-scale production of the carbohydrate portion of the sialyl-Tn epitope, α-Neup5Ac-(2-6)-D-GalpNAc, through bacterial coupling. Carbohyd. Res.330:439-443. [PubMed]
13. Endo, T., S. Koizumi, K. Tabata, S. Kakita, and A. Ozaki. 1999. Large-scale production of N-acetyllactosamine through bacterial coupling. Carbohydr. Res.316:179-183. [PubMed]
14. Gilbert, M., R. Bayer, A. M. Cunningham, S. Defrees, Y. H. Gao, D. C. Watson, N. M. Young, and W. W. Wakarchuk. 1998. The synthesis of sialylated oligosaccharides using a CMP-Neu5Ac synthetase/sialyltransferase fusion. Nat. Biotechnol.16:769-772. [PubMed]
15. Hindsgaul, O., K. J. Kaur, U. B. Gokhale, G. Srivastava, G. Alton, and M. M. Palcic. 1991. Use of glycosyltrasferses in synthesis of unnatural oligosaccharide analogs. ACS Symp. Ser.466:38-50.
16. Ichikawa, Y., R. Wang, and C.-H. Wong. 1994. Regeneration of sugar nucleotide for enzymatic oligosaccharide synthesis. Methods Enzymol.247:107-127. [PubMed]
17. Johnson, K. F. 1999. Synthesis of oligosaccharides by bacterial enzymes. Glycoconjugate J.16:141-146. [PubMed]
18. Karlsson, K. A. 1995. Microbial recognition of target-cell glycoconjugates. Curr. Opin. Struct. Biol.5:622-635. [PubMed]
19. Koeller, K. M., and C.-H. Wong. 2000. Synthesis of complex carbohydrates and glycoconjugates: enzyme-based and programmable one-pot strategies. Chem. Rev.100:4465-4493. [PubMed]
20. Koizumi, S., T. Endo, K. Tabata, and A. Ozaki. 1998. Large-scale production of UDP-galactose and globotriose by coupling metabolically engineered bacteria. Nat. Biotechnol.16:847-850. [PubMed]
21. Kyowa Hakko Kogyo Co. Ltd. (S. Koizumi, H. Kawano, K. Kino, and A. Ozaki). April1996. Processes for producing sugar nucleotides and complex carbohydrates. World Intellectual Property Organization, WO-09611247.
22. Kyowa Hakko Kogyo Co. Ltd. (S. Koizumi, K. Sosaki, T. Endo, K. Tabata, and A. Ozaki). October 1998. Processes for producing sugar nucleotides and complex carbohydrates. World Intellectual Property Organization, WO-09612343.
23. Laemmli, U. K. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227:680-685. [PubMed]
24. Lindberg, A. A., J. E. Brown, N. Strömberg, M. Westling-Ryd, J. E. Schultz, and K.-A. Karlsson. 1987. Identification of the carbohydrate receptor for Shiga toxin produced by Shigella dysenteriae type 1. J. Biol. Chem.262:1779-1785. [PubMed]
25. Ling, H., A. Boodhoo, B. Hazes, M. D. Cummings, G. D. Armstrong, J. L. Brunton, and R. J. Read. 1998. Structure of the Shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3. Biochemistry37:1777-1788. [PubMed]
26. Lingwood, C. A. 1996. Role of verotoxin receptors in pathogenesis. Trends Microbiol.4:147-153. [PubMed]
27. Lovett, R. A. 1998. Training a molecular gun on killer E. coli. Science282:1404.. [PubMed]
28. Lowry, O. H., N. J. Rosebrough, A. L. Farr, and R. J. Randall. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem.193:265-275. [PubMed]
29. Mackenzie, L. F., Q. P. Wang, R. A. J. Warren, and S. G. Withers. 1998. Glycosynthases: mutant glycosidases for oligosaccharide synthesis. J. Am. Chem. Soc.120:5583-5584.
30. Nakai, T., T. Konishi, X. Q. Zhang, R. Chollet, N. Tonouchi, T. Tsuchida, F. Yoshinaga, H. Mori, F. Sakai, and T. Hayashi. 1998. An increase in apparent affinity for sucrose of mung bean sucrose synthase is caused by in vitro phosphorylation or directed mutagenesis of Ser11. Plant Cell Physiol.39:1337-1341. [PubMed]
31. Nakano, H., T. Yamazaki, M. Ikeda, H. Masai, S. Miyatake, and T. Saito. 1994. Purification of glutathione S-transferase fusion proteins as a non-degraded form by using a protease-negative E. coli strain, AD202. Nucleic Acids Res.11:543-544. [PMC free article][PubMed]
32. Nataro, J. P., and J. B. Kaper. 1998. Diarrheagenic Escherichia coli.Clin. Microbiol. Rev.11:142-201. [PMC free article][PubMed]
33. Neose Technologies Inc. (S. DeFrees, R. J. Bayer, and M. Ratcliffe). February 2000. Enzymatic synthesis of oligosaccharides. U.S. Patent US-0603061 5.
34. Palcic, M. M., and O. Hindsgaul. 1996. Glycosyltransferases in the synthesis of oligosaccharide analogs. Trends Glycosci. Glycotechnol.8:37-49.
35. Palcic, M. M. 1999. Biocatalytic synthesis of oligosaccharides. Curr. Opin. Biotechnol.10:616-624. [PubMed]
36. Paton, A. W., R. Morona, and J. C. Paton. 2000. A new biological agent for treatment of Shiga toxigenic Escherichia coli infections and dysentery in humans. Nat. Med.6:265-270. [PubMed]
37. Peter, M. G., and C. A. Lingwood. 2000. Apparent cooperativity in multivalent verotoxin-globotriaosyl ceramide binding: kinetic and saturation binding studies with [125I]verotoxin. Biochim. Biophys. Acta1501:116-124. [PubMed]
38. Porchia, A. C., L. Curatti, and G. L. Salerno. 1999. Sucrose metabolism in cyanobacteria: sucrose synthase from Anabaena sp. strain PCC 7119 is remarkably different from the plant enzymes with respect to substrate affinity and amino-terminal sequence. Planta210:34-40. [PubMed]
39. Porchia, A. C., and G. L. Salerno. 1996. Sucrose biosynthesis in a prokaryotic organism: presence of two sucrose-phosphate synthases in Anabaena with remarkable differences compared with the plant enzymes. Proc. Natl. Acad. Sci. USA93:13600-13604. [PMC free article][PubMed]
40. Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.
41. Schweizer, F., and O. Hindsgaul. 1999. Combinatorial synthesis of carbohydrates. Curr. Opin. Chem. Biol.3:291-298. [PubMed]
42. Scigelova, M., S. Singh, and D. H. G. Crout. 1999. Glycosidases—a great synthetic tool. J. Mol. Catalysis B6:483-494.
43. Sujino, K., T. Uchiyama, O. Hindsgaul, N. O. L. Seto, W. W. Wakarchuk, and M. M. Palcic. 2000. Enzymatic synthesis of oligosaccharide analogues: evaluation of UDP-Gal analogues as donors for three retaining α-galactosyltransferases. J. Am. Chem. Soc.122:1261-1269.
44. Takao, T., T. Tanabe, Y.-M. Hong, Y. Shimonishi, H. Kurazono, T. Yutsudo, C. Sasakawa, M. Yoshikawa, and Y. Takeda. 1988. Identity of molecular structure of Shiga-like toxin I (VT1) from Escherichia coli O157:H7 with that of Shiga toxin. Microb. Pathog.5:357-369. [PubMed]
45. Wakarchuk, W. W., A. Cunningham, D. C. Watson, and M. Young. 1998. Role of paired basic residues in the expression of active recombinant galactosyltransferases from the bacterial pathogen Neisseria meningitidis. Protein Eng.11:295-302. [PubMed]
46. Wang, P., G.-J. Shen, Y.-F. Wang, Y. Ichikawa, and C.-H. Wong. 1993. Enzymes in oligosaccharide synthesis—active-domain overproduction, specificity study, and synthetic use of an α-1,2-mannosyltransferase with regeneration of GDP-Man. J. Org. Chem.58:3985-3990.
47. Watt, G. M., P. A. Lowden, and S. L. Flitsch. 1997. Enzyme-catalyzed formation of glycosidic linkages. Curr. Opin. Struct. Biol.7:652-660. [PubMed]
48. Wong, C.-H., S. L. Haynie, and G. M. Whitesides. 1982. Enzyme-catalyzed synthesis of N-acetyllactosamine with in situ regeneration of uridine 5′-diphosphate glucose and uridine 5′-diphosphate galactose. J. Org. Chem.47:5418.
49. Wong, C.-H., R. Wang, and Y. Ichikawa. 1992. Regeneration of sugar nucleotide for enzymatic oligosaccharide synthesis—use of Gal-1-phosphate uridyltransferase in the regeneration of UDP-galactose, UDP-2-deoxygalactose, and UDP-galactosamine. J. Org. Chem.57:4343-4344.
50. Yamasa Corporation (T. Noguchi and T. Shiba). February 1998. Enzymic preparation of nucleotide 5′-triphosphates and its application in glycosylation reaction. World Intellectual Property Organization, WO-09622614.
51. Zervosen, A., and L. Elling. 1996. A novel three-enzyme reaction cycle for the synthesis of N-acetyllactosamine with in situ regeneration of uridine 5′-diphosphate glucose and uridine 5′-diphosphate galactose. J. Am. Chem. Soc.118:1836-1840.