Synthesis and proinflammatory properties of an analog of Rhizobial lipid A that contains an ether-linked lipid

CARB 42

Mahalakshmi Vasan, mvasan@chem.uga.edu1, Yanghui Zhang1, Margreet A. Wolfert, mwolfert@ccrc.uga.edu2, and Geert-Jan Boons, gjboons@ccrc.uga.edu2. (1) Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602, (2) Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, University of Georgia, Athens, GA 30602
Morbidity and mortality rates associated with the 375,000 cases of Gram-negative sepsis occurring annually in the United States have been strongly linked to the presence of lipopolysaccharide (LPS) in the blood of affected patients. LPS, a structural component of Gram-negative bacteria, is one of the most potent stimulators of the inflammatory system. More specifically, the lipid A region of LPS initiates the production of a variety of host-derived inflammatory mediators that are responsible for systemic inflammatory responses, including fever, hypotension, initiation of intravascular coagulation, metabolic acidosis, and increased susceptibility to pathogens. We have found that Rhizobial LPS does not stimulate human monocytes. More importantly, it significantly inhibits LPS dependent synthesis of TNF. We have developed a facile approach for the synthesis of a rhizobial lipid-A derivative in which an ether linked hydrocarbon chain is attached to the C-3 at the reducing sugar. This ether-linked compound is significantly more stable than the natural ester counter part. The proinflammatory properties of this compound have been studies and the results compared with that of natural rhizobial LPS.
 

General Posters
6:00 PM-8:00 PM, Tuesday, 28 March 2006 Georgia World Congress Center -- Ex. Hall B4, Poster

Division of Carbohydrate Chemistry

The 231st ACS National Meeting, Atlanta, GA, March 26-30, 2006