Endotoxin pp 3-11 | Cite as

Chemical Synthesis of Endotoxin

  • S. Kusumoto
  • N. Kusunose
  • M. Imoto
  • T. Kamikawa
  • T. Shiba
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 256)


Total synthesis of lipid A’s of Escherichia coli and many other bacterial species achieved in our laboratory (6, 7, 8) contributed not only to confirm their proposed chemical structures but also to establish unequivocally that these phosphorylated polyacyl glucosamine disaccharide with definite structures are responsible for most of the endotoxic activities of bacterial lipopolysaccharide (LPS) (4, 5). Furthermore, precise study on the biological activities could be carried out in relation to the acylation or phosphorylation patterns of the molecules with these pure synthetic preparations of lipid A’s in hand (12, 13). Immunogenicity and antigenicity of lipid A could be analyzed as well (1, 2). As the results, evidences were obtained which indicated that the toxic and other biological activities of endotoxin could be separated by adequate modification of the structure such as distribution of the acyl groups. One might thus be able to utilize some of the beneficial biological activities by further research in this line.


Boron Trifluoride Lithium Aluminum Hydride Boron Trifluoride Etherate Synthetic Lipid Centrifugal Partition Chromatography 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Arata, S., Mashimo, J., Kasai, N. Okuda, K., Aihara, Y., Kotani, S., Takada, H., Shimamoto, T., and Kusunose, N., 1988, Characterization of monoclonal lipid A antibodies with synthetic lipid a analogues. FEBS Microbiology Letters. 49: 479.Google Scholar
  2. 2.
    Brade, L., Brandenburg, K., Kuhn, H.-M., Kusumoto, S., Macher, T.I., Rietschel, E. Th., and Brade, H. 1987, The immunogenicity and antigeni-city of lipid A are influenced by its physicochemical state and environment. Infect. Immun. 55: 2636.Google Scholar
  3. 3.
    Christian, R., Schulz, G., Waldstatten, P. and Unger, F. M., 1984, Zur Struktur der 3-Deoxyoktulosonsàure- (KDO-) Region des Lipopolysaccharids von Salmonella minnesota Re 595. Tetrahedron Lett. 25: 3433.CrossRefGoogle Scholar
  4. 4.
    Galanos, C. Lehmann, V., Luderitz, O., Rietschel, E. Th., Westphal, O., Brade, H., Brade, L., Freudenberg, M. A., Hansen-Hagge, T. Luderitz, T., Mckenzie, G., Schade, U. Strittmatter, W., Tanamoto, K., Zähringer, U., Imoto, M., Yoshimura, H., Yamamoto, M., Shimamoto, T., Kusumoto, S., and Shiba, T., 1984, Endotoxic properties of chemically synthesized lipid A part structures — comparison of synthetic lipid A precursor and synthetic analogues with biosynthetic lipid A precursor and free lipid A. Eur. J. Biochem. 140: 221.Google Scholar
  5. 5.
    Galanos, C., Luderitz, O. Rietschel, E. Th., Westphal, O., Brade, H., Brade, L., Freudenberg. M., Schade, U. Imoto, M., Yoshimura, H., Kusumoto, S., and Shiba, T., 1985, Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities. Eur. J. Biochem. 148: 1.Google Scholar
  6. 6.
    Imoto, M., Yoshimura. H., Yamamoto, M., Shimamoto, T., Kusumoto, S. and Shiba, T., 1984, Chemical synthesis of phosphorylated tetraacyl disaccharide corresponding to a biosynthetic precursor of lipid A. Tetrahedron Lett. 25: 2667.Google Scholar
  7. 7.
    Imoto, M., Yoshimura, H., Sakaguchi, N. Kusumoto, S., and Shiba, T., 1985, Total synthesis of Escherichia coli lipid A. Tetrahedron Lett. 26: 1545.Google Scholar
  8. 8.
    Imoto, M., Yoshimura, H., Shimamoto, T., Sakaguchi, N., Kusumoto, S., and Shiba, T., 1987, Total synthesis of Escherichia coli Lipid A, the endotoxically active principle of cell-surface lipopolysaccharide. Bull. Chem. Soc. Jpn. 60: 2205.CrossRefGoogle Scholar
  9. 9.
    Imoto, M., Kusumoto, S. and Shiba, T. 1987. A new synthesis of 3-deoxy-D-manno-2-octulosonic acid ( KDO) from D-mannose. Tetrahedron Lett. 28: 6235.Google Scholar
  10. 10.
    Imoto, M., Kusunose, N., Matsuura, Y., Kusumoto, S., and Shiba, T., 1987, Preparation of novel pyranosyl fluoride of 3-deoxy-D-manno-2-octulosonic acid (KDO) feasible for synthesis of KDO a -glycosides. Tetrahedron Lett. 28: 6277.CrossRefGoogle Scholar
  11. 11.
    Imoto, M., Kusunose, N., Kusumoto, S., and Shiba, T., 1988, Synthetic approach to bacterial lipopolysaccharide, preparation of trisaccharide part structure containing KDO and 1-dephospho lipid A. Tetrahedron Lett. 29: 2227.CrossRefGoogle Scholar
  12. 12.
    Kanegasaki, S., Tanamoto, K., Yasuda, T., Homma, J. Y., Matsuura, M., Nakatsuka, M., Kumazawa, Y., Yamamoto, A., Shiba, T., Kusumoto, S., Imoto, M., Yoshimura, H., and Shimamoto, T., 1986, Structure-activity relationship of lipid A: comparison of biological activity of natural and synthetic lipid A’s with different fatty acid compositions. J. Biochem. 99: 1203.PubMedGoogle Scholar
  13. 13.
    Kotani, S., Takada, H., Takahashi, I., Ogawa, T., Tsujimoto, M., Shimauchi, H., Ikeda, T., Okamura, H., Tamura, T., Harada, K., Tanaka, S., Shiba, T., Kusumoto, S., and Shimamoto, T., 1986, Immunobiological activities of synthetic lipid A analogs with low endotoxicity. Infect. Immun. 54: 673.Google Scholar
  14. 14.
    Paulsen, H. and Schüller, M., 1987, Synthese von KDO-haltigen Lipoid-AAnaloga. Liebigs Ann. Chem. 249.Google Scholar
  15. 15.
    Rietschel, E. Th., Brade, L., Schade, U., Seydel, U., Zähringer, U., Kusumoto, S., and Brade, H., 1988, Bacterial endotoxins: properties and structure of biologically active domains, “Surface Structures of Microorganisms and their Interaction with Mammalian Host,” ed. U. Schwartz and M. Richmond, Verlag Chemie, Weinheim.Google Scholar
  16. 16.
    Zähringer, U., Lindner, B., Seydel, U., Rietschel, E. Th., Naoki, H. Unger, F. M., Imoto, M., Kusumoto, S., and Shiba, T., 1985, Structure of de-0-acylated lipopolysaccharide from Escherichia coli Re mutant strain F 515. Tetrahedron Lett. 26: 6321.Google Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • S. Kusumoto
    • 1
  • N. Kusunose
    • 1
  • M. Imoto
    • 1
  • T. Kamikawa
    • 1
  • T. Shiba
    • 1
  1. 1.Department of Chemistry, Faculty of ScienceOsaka UniversityToyonaka Osaka 560Japan

Personalised recommendations