Anti-endotoxin agents. 2. Pilot high-throughput screening for novel lipopolysaccharide-recognizing motifs in small molecules.

ABSTRACT: Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are an integral part of the outer leaflet of the outer-membrane of Gram-negative bacteria. Lipopolysaccharides play a pivotal role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient, worldwide. The sequestration of circulatory endotoxin may be a viable therapeutic strategy for the prophylaxis and treatment of Gram-negative sepsis. We have earlier shown that the pharmacophore necessary for small molecules to bind LPS is simple, comprising of two protonatable cationic functions separated by about 15 A, permitting the simultaneous interaction with the negatively charged phosphates on lipid A, the toxically active center of endotoxin. In this report, we employ high-throughput screening method

SUBMITTER: Wood SJ 

PROVIDER: S-EPMC1360204 | biostudies-literature | 2004 Dec

REPOSITORIES: biostudies-literature