Document Detail

The influence of the long chain fatty acid on the antagonistic activities of Rhizobium sin-1 lipid A.
MedLine Citation:
PMID:  17513113     Owner:  NLM     Status:  MEDLINE    
The lipid A from nitrogen-fixing bacterial species Rhizobium sin-1 is structurally unusual due to lack of phosphates and the presence of a 2-aminogluconolactone and a very long chain fatty acid, 27-hydroxyoctacosanoic acid (27OHC28:0), moiety. This structurally unusual lipid A can antagonize TNF-alpha production by human monocytes induced by Escherichia coli LPS. To establish the relevance of the unusual long chain 27-hydroxyoctacosanoic acid for antagonistic properties, a highly convergent strategy for the synthesis of several derivatives of the lipid A of R. sin-1 has been developed. Compound 1 is a natural R. sin-1 lipid A having a 27-hydroxyoctacosanoic acid at C-2', compound 2 contains an octacosanoic acid moiety at this position, and compound 3 is modified by a short chain tetradecanoic acid. Cellular activation studies with a human monocytic cell line have shown that the octacosanoic acid is important for optimal antagonistic properties. The hydroxyl of the natural 27-hydroxyoctacosanoic moiety does, however, not account for inhibitory activity. The resulting structure-activity relationships are important for the design of compounds for the treatment of septic shock.
Yanghui Zhang; Margreet A Wolfert; Geert-Jan Boons
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-05-06
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  15     ISSN:  0968-0896     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-06     Completed Date:  2007-08-08     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  4800-12     Citation Subset:  IM    
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MeSH Terms
Cell Line
Fatty Acids / chemical synthesis,  chemistry*,  pharmacology*
Lipid A / antagonists & inhibitors*,  metabolism
Molecular Structure
Monocytes / drug effects,  metabolism
Rhizobium / metabolism*
Structure-Activity Relationship
Grant Support
Reg. No./Substance:
0/Fatty Acids; 0/Lipid A

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