Lipopolysaccharide sequestrants: structural correlates of activity and toxicity in novel acylhomospermines.

ABSTRACT: Lipopolysaccharides (LPS), otherwise termed "endotoxins", are outer membrane constituents of Gram-negative bacteria. Lipopolysaccharides play a key role in the pathogenesis of "septic shock", a major cause of mortality in the critically ill patient. Therapeutic options aimed at limiting downstream systemic inflammatory processes by targeting lipopolysaccharide do not exist at the present time. We have defined the pharmacophore necessary for small molecules to specifically bind and neutralize LPS and, using animal models of sepsis, have shown that the sequestration of circulatory LPS by small molecules is a therapeutically viable strategy. In this paper, the interactions of a series of acylated homologated spermine compounds with LPS have been characterized. The optimal acyl chain length fo

SUBMITTER: Miller KA 

PROVIDER: S-EPMC1360202 | biostudies-literature | 2005 Apr

REPOSITORIES: biostudies-literature