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Science 15 January 1993:
Vol. 259. no. 5093, pp. 361 - 365
DOI: 10.1126/science.8420003
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Articles

Science, Vol 259, Issue 5093, 361-365
Copyright © 1993 by American Association for the Advancement of Science

articles

Molecular mapping and detoxification of the lipid A binding site by synthetic peptides

A Rustici, M Velucchi, R Faggioni, M Sironi, P Ghezzi, S Quataert, B Green, and M Porro

Biosynth Research Laboratories, Siena, Italy.

Endotoxin [lipopolysaccharide (LPS)], the major antigen of the outer membrane of Gram-negative bacteria, consists of a variable-size carbohydrate chain that is covalently linked to N,O-acylated beta-1,6-D-glucosamine disaccharide 1,4'-bisphosphate (lipid A). The toxic activity of LPS resides in the lipid A structure. The structural features of synthetic peptides that bind to lipid A with high affinity, detoxify LPS in vitro, and prevent LPS-induced cytokine release and lethality in vivo were defined. The binding thermodynamics were comparable to that of an antigen-antibody reaction. Such synthetic peptides may provide a strategy for prophylaxis and treatment of LPS-mediated diseases.


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