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Science 7 April 1995:
Vol. 268. no. 5207, pp. 80 - 83
DOI: 10.1126/science.7701344
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Articles

Science, Vol 268, Issue 5207, 80-83
Copyright © 1995 by American Association for the Advancement of Science

articles

E5531, a pure endotoxin antagonist of high potency

WJ Christ, O Asano, AL Robidoux, M Perez, Y Wang, GR Dubuc, WE Gavin, LD Hawkins, PD McGuinness, MA Mullarkey, and al. et

Elsai Research Institute, Andover, MA 01810-2441, USA.

Shock due to Gram-negative bacterial sepsis is a consequence of acute inflammatory response to lipopolysaccharide (LPS) or endotoxin released from bacteria. LPS is a major constituent of the outer membrane of Gram-negative bacteria, and its terminal disaccharide phospholipid (lipid A) portion contains the key structural features responsible for toxic activity. Based on the proposed structure of nontoxic Rhodobacter capsulatus lipid A, a fully stabilized endotoxin antagonist E5531 has been synthesized. In vitro, E5531 demonstrated potent antagonism of LPS-mediated cellular activation in a variety of systems. In vivo, E5531 protected mice from LPS-induced lethality and, in cooperation with an antibiotic, protected mice from a lethal infection of viable Escherichia coli.


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