Current Topics in Medicinal Chemistry - Volume 4, Issue 11, 2004

The initial systematic investigations of the toxic effects of putrescent material of plant and animal origin by Peter L. Panum (around 1856), led to the conclusion that the toxic principle originates from living microorganisms. Since then research on endotoxin, later defined as lipopolysaccharides (LPS), has become a major subject of immunological and immunochemical research. Great interest in LPS, the integral components of t Read More

Lipopolysaccharide (LPS) is the principal initiator of septic shock and it is to a large extent responsible for post-operative mortality. The use of antibiotics is still the most successful therapy against infection that may lead to sepsis and septic shock. With the advent of antibiotic resistant strains like MRSA the usefulness of conventional antibiotics is declining and new treatment strategies for LPS-mediated septic shock are Read More

Molecules of endotoxin (lipopolysaccharides, LPS), forming a unique molecular class with peculiar physicochemical properties, impart a very important role in the formation and function of the outer membrane (OM). The latter is strictly asymmetric with the LPS monolayer forming the outer leaflet and the phospholipid (PL) monolayer forming the inner leaflet. Thus, the OM builds a functional lipid environment for the O Read More

Endotoxin, from the outer membrane of Gram-negative bacteria, has been implicated as the etiological agent of a variety of pathologies ranging from relatively mild (fever) to lethal (septic shock, organ failure, and death). While endotoxin (also known as lipopolysaccharide or LPS) is a complex heterogeneous molecule, the toxic portion of LPS (the lipid A portion) is relatively similar across a wide variety of pathogenic st Read More

Neutralization and sequestration of bacterial lipopolysaccharide which plays a key role in gram-negative sepsis is required to block the progression of sepsis at early stages in addition to destroying bacteria. Many of the host defense peptides which have antimicrobial activity are also able to bind to and neutralize LPS, however, these two activities do not necessarily correlate. Due to its toxicity application of polymyxin B as the pro Read More

Lipopolysaccharide (LPS) induced Gram-negative sepsis and septic shock remain lethal in up to 60 % of cases, and LPS antagonists that neutralize its endotoxic action are the subject of intensive research. The molecular motifs of specific binding of LPS by antiendotoxin proteins and peptides may lead to an understanding of LPS action at the atomic level and provide clues for the development of new immunomodulatory comp Read More