1995 Fiscal Year Final Research Report Summary
Elucidation of the chemical structure possessing antagonistic activity of endotoxin using chemical synthesis
| Project/Area Number |
06670313
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
TANAMOTO Kenich National Institute of Health Sciences Microbiology, Head, 衛生微生物部, 室長 (60107430)
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| Co-Investigator(Kenkyū-buntansha) |
HAISHIMA Yuji National Institute of Health Sciences Microbiology, Researcher, 衛生微生物部, 研究員 (80228379)
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| Project Period (FY) |
1994 – 1995
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| Keywords | endotoxin / lipid A / antagonist / synthetic lipid A / succinylation |
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| Research Abstract |
In the present study, the rple of the free hydroxyl groups of some representative lipid A preperations synthesized chemically, E.coli type 506, Salmonella type 516 and disaccharide lipid A precursor 406, for their endotoxic activity was studied with the aim to clarify the chemical factors which convert the biological active structures to inactive and antagonistic form. The results show that neither complete lipid A structure (506 and 516) lost its biological activity as a result of succinylation or acetylation, indicating that the hydroxyl groups in these lipid As need not present in free form. In contrast, the disaccharide precursor 406 loses all of its biological activity completely upon chemical modification and is converted to an endotoxin antagonist. These findings suggest taat, regardless of the nature of the substituent, substitution of the hydroxyl groups of 406 is important both in changing the endotoxically active lipid A struture to an inactive form and to an endotoxin antagonist. The difference in chemical structure between the succinylated form of E.coli type lipid A and 406 is only the substitution of two hydroxyl residues of 3-hydroxy myristic acid of the nonreducing glucosamine. Therefore it was indicated that the substitution of the hydroxyl redidues at these positions play an important role in its activity in transformation to an antagonistic structure.
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