The Influence of the Long Chain Fatty Acid on the Antagonistic Activities of Rhizobium sin-1 Lipid A

Yanghui Zhang, Margreet A Wolfert, Geert-Jan Boons

Bioorg Med Chem. 2007 Jul 15;15(14):4800-12.

PMID: 17513113

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP506489	Octacosanoic acid		506-48-9	Price