Effect of stereospecificity of chemically synthesized lipid A-subunit analogues GLA-27 and GLA-40 on the expression of immunopharmacological activities
| Autor: | J. Yuzuru Homma, S. Ikeda, Yoshio Kumazawa, Mitsunobu Nakatsuka, Chiaki Nishimura, Makoto Kiso, Akira Hasegawa, Akihiro Yamamoto, Hiroaki Takimoto |
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| Rok vydání: | 1987 |
| Předmět: |
Immunology
Stereoisomerism Lymphocyte Activation Chemical synthesis Lipid A Mice Structure-Activity Relationship Stereospecificity Phagocytosis Viral Interference Immunology and Allergy Structure–activity relationship Animals cardiovascular diseases Glycoproteins chemistry.chemical_classification B-Lymphocytes biology Tumor Necrosis Factor-alpha Acid phosphatase nutritional and metabolic diseases Macrophage Activation Cytostasis Enzyme Biochemistry chemistry Antibody Formation biology.protein lipids (amino acids peptides and proteins) Lysosomes hormones hormone substitutes and hormone antagonists Cell Division |
| Zdroj: | European journal of immunology. 17(5) |
| ISSN: | 0014-2980 |
| Popis: | Tumor necrosis factor (TNF)-inducing, mitogenic, polyclonal B cell activation (PBA), macrophage activation and antiviral activities of chemically synthesized lipid A-subunit analogues, GLA-27 and GLA-40, were investigated. The structure of GLA-27 comprises 4-O-phosphono-D-glucosamine carrying tetradecanoyl and 3-tetradecanoyloxytetradecanoyl [C14-O-(C14)] groups as the 3-O- and 2-N-acyl substituents, respectively. GLA-40 is a 1-deoxy compound of GLA-27. The activities of stereoisomers, (R) and (S) forms at the C3 position of the C14-O-(C14) group, of both compounds were also investigated. TNF-inducing activity of the (S) isomers of GLA-27 and GLA-40 was stronger than that of the (R) isomers while the (R) isomers exhibited stronger mitogenic and PBA activities than the (S) isomers. With respect to macrophage activation such as phagocytosis, acid phosphatase and N-acetyl-beta-D-glucosaminidase activity as cellular lysosomal enzymes and cytostasis, peritoneal macrophages obtained from mice administered i.p. with test samples showed significant activities. Among stereoisomers of GLA-27, the (R) isomer exhibited somewhat stronger phagocytic and lysosomal enzyme activities than those of the (S) isomer while there was no appreciable difference in the activities between the isomers of GLA-40. Significant cytostasis-inducing activity was observed in stereoisomers tested. All of the isomers showed remarkable antiviral activity against vaccinia virus. |
| Databáze: | OpenAIRE |
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