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. 1987 Sep;55(9):2287–2289. doi: 10.1128/iai.55.9.2287-2289.1987

Biological activities of chemically synthesized 2-keto-3-deoxyoctonic acid-(alpha 2----6)-D-glucosamine analogs of lipid A.

T Shimizu, S Akiyama, T Masuzawa, Y Yanagihara, S Nakamoto, K Achiwa
PMCID: PMC260692  PMID: 3623704

Abstract

The mitogenicity, lethal toxicity, and Shwartzman reaction of three derivatives of chemically synthesized 2-keto-3-deoxyoctonic acid-linked 2,3-diacyloxyacylglucosamine-4-phosphate (KDO-GlcN-4-P) were determined. The compounds, A-301 (with di-3-hexadecanoyloxytetradecanoyl at the C-2 and C-3 positions), A-303 (di-3-tetradecanoyloxytetradecanoyl), and A-305 (3-dodecanoyloxytetradecanoyl and 3-tetradecanoyloxytetradecanoyl), induced a significant incorporation of [3H]thymidine into splenocytes of C57BL/6 mice. The compounds A-301 and A-303 showed lethality at a high dose of 50 micrograms per mouse in C57BL/6 mice sensitized with D-galactosamine, whereas A-305 caused toxicity even at a dose of 10 micrograms per mouse. However, the three compounds did not elicit the local Shwartzman reaction in rabbits. These findings indicate that the addition of 2-keto-3-deoxyoctonic acid enhances the mitogenic activity of 2,3-diacyloxyacylglucosamine-4-phosphate but does not affect the lethal toxicity and the induction of Shwartzman reaction.

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Selected References

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  1. Amano K., Fujita H., Sato T., Sasaki H., Yoshida Y., Fukushi K. [Biological activities of chemically-treated glycolipids from Salmonella minnesota Re-mutant]. Nihon Saikingaku Zasshi. 1985 Jul;40(4):775–782. doi: 10.3412/jsb.40.775. [DOI] [PubMed] [Google Scholar]
  2. Amano K., Ribi E., Cantrell J. L. Structural requirements of endotoxic glycolipid for antitumor and toxic activity. J Biochem. 1983 May;93(5):1391–1399. doi: 10.1093/oxfordjournals.jbchem.a134274. [DOI] [PubMed] [Google Scholar]
  3. Galanos C., Freudenberg M. A., Reutter W. Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5939–5943. doi: 10.1073/pnas.76.11.5939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Galanos C., Hansen-Hagge T., Lehmann V., Lüderitz O. Comparison of the capacity of two lipid A precursor molecules to express the local Shwartzman phenomenon. Infect Immun. 1985 May;48(2):355–358. doi: 10.1128/iai.48.2.355-358.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Homma J. Y., Matsuura M., Kanegasaki S., Kawakubo Y., Kojima Y., Shibukawa N., Kumazawa Y., Yamamoto A., Tanamoto K., Yasuda T. Structural requirements of lipid A responsible for the functions: a study with chemically synthesized lipid A and its analogues. J Biochem. 1985 Aug;98(2):395–406. doi: 10.1093/oxfordjournals.jbchem.a135294. [DOI] [PubMed] [Google Scholar]
  6. Kotani S., Takada H., Tsujimoto M., Ogawa T., Takahashi I., Ikeda T., Otsuka K., Shimauchi H., Kasai N., Mashimo J. Synthetic lipid A with endotoxic and related biological activities comparable to those of a natural lipid A from an Escherichia coli re-mutant. Infect Immun. 1985 Jul;49(1):225–237. doi: 10.1128/iai.49.1.225-237.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kumazawa Y., Matsuura M., Homma J. Y., Nakatsuru Y., Kiso M., Hasegawa A. B cell activation and adjuvant activities of chemically synthesized analogues of the nonreducing sugar moiety of lipid A. Eur J Immunol. 1985 Feb;15(2):199–201. doi: 10.1002/eji.1830150218. [DOI] [PubMed] [Google Scholar]
  8. Lüderitz O., Galanos C., Lehmann V., Mayer H., Rietschel E. T., Weckesser J. Chemical structure and biological activities of lipid A's from various bacterial families. Naturwissenschaften. 1978 Nov;65(11):578–585. doi: 10.1007/BF00364907. [DOI] [PubMed] [Google Scholar]
  9. Matsuura M., Kojima Y., Homma J. Y., Kubota Y., Yamamoto A., Kiso M., Hasegawa A. Biological activities of chemically synthesized analogues of the nonreducing sugar moiety of lipid A. FEBS Lett. 1984 Feb 27;167(2):226–230. doi: 10.1016/0014-5793(84)80131-3. [DOI] [PubMed] [Google Scholar]
  10. Nakamoto S., Achiwa K. Synthesis of biologically active tetraacetyl-3-deoxy-D-manno-2-octulosonic acid(KDO)-(alpha 2----6)-D-glucosamine analogs of lipid A. Chem Pharm Bull (Tokyo) 1986 May;34(5):2302–2305. doi: 10.1248/cpb.34.2302. [DOI] [PubMed] [Google Scholar]
  11. Nakamoto S., Takahashi T., Ikeda K., Achiwa K. Efficient synthesis of novel monosaccharide analogs of lipids A. Chem Pharm Bull (Tokyo) 1985 Sep;33(9):4098–4101. doi: 10.1248/cpb.33.4098. [DOI] [PubMed] [Google Scholar]
  12. Nishijima M., Amano F., Akamatsu Y., Akagawa K., Tokunaga T., Raetz C. R. Macrophage activation by monosaccharide precursors of Escherichia coli lipid A. Proc Natl Acad Sci U S A. 1985 Jan;82(2):282–286. doi: 10.1073/pnas.82.2.282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Raetz C. R., Purcell S., Takayama K. Molecular requirements for B-lymphocyte activation by Escherichia coli lipopolysaccharide. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4624–4628. doi: 10.1073/pnas.80.15.4624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Seydel U., Lindner B., Wollenweber H. W., Rietschel E. T. Structural studies on the lipid A component of enterobacterial lipopolysaccharides by laser desorption mass spectrometry. Location of acyl groups at the lipid A backbone. Eur J Biochem. 1984 Dec 17;145(3):505–509. doi: 10.1111/j.1432-1033.1984.tb08585.x. [DOI] [PubMed] [Google Scholar]
  15. Shimizu T., Akiyama S., Masuzawa T., Yanagihara Y., Nakamoto S., Achiwa K. Antitumor activity and lethal toxicity of chemically synthesized tetraacetyl-2-keto-3-deoxyoctonic acid-(alpha 2---6)-D-glucosamine analogues of lipid A. Chem Pharm Bull (Tokyo) 1987 Feb;35(2):873–876. doi: 10.1248/cpb.35.873. [DOI] [PubMed] [Google Scholar]
  16. Shimizu T., Akiyama S., Masuzawa T., Yanagihara Y., Nakamoto S., Achiwa K. Mitogenic activity of chemically synthesized tetraacetyl-2-keto-3-deoxyoctonic acid-(alpha 2----6)-D-glucosamine analogues of lipid A. Chem Pharm Bull (Tokyo) 1986 May;34(5):2310–2313. doi: 10.1248/cpb.34.2310. [DOI] [PubMed] [Google Scholar]
  17. Shimizu T., Akiyama S., Masuzawa T., Yanagihara Y., Nakamoto S., Takahashi T., Ikeda K., Achiwa K. Comparison of biological activities of chemically synthesized monosaccharide analogues of reducing and nonreducing sugar moieties of lipid A. Chem Pharm Bull (Tokyo) 1986 Dec;34(12):5169–5175. [PubMed] [Google Scholar]
  18. Shimizu T., Nitta M., Itoh Y., Yanagihara Y., Mifuchi I. Mitogenicity and adjuvanticity of a marine bacterium, Vibrio anguillarum, in mice. Microbiol Immunol. 1981;25(9):929–937. doi: 10.1111/j.1348-0421.1981.tb00097.x. [DOI] [PubMed] [Google Scholar]
  19. Sidorczyk Z., Zähringer U., Rietschel E. T. Chemical structure of the lipid A component of the lipopolysaccharide from a Proteus mirabilis Re-mutant. Eur J Biochem. 1983 Dec 1;137(1-2):15–22. doi: 10.1111/j.1432-1033.1983.tb07789.x. [DOI] [PubMed] [Google Scholar]

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