Science · 1995 · 323 citations · 20 references
Veterinary MedicineImmunologyMicrobiologyInflammationInnate ImmunitySepsisAntibacterial PharmacologyBacterial PathogenesisBacterial ToxinsInnate Immune RecognitionInnate Immune ResponseSepsis PathophysiologyAcute Inflammatory InjuryAcute Inflammatory ResponseBacterial Lipopolysaccharide RecognitionEndotoxin ToxicityEndotoxin-mediated DiseaseEndotoxin-mediated InflammationEscherichia ColiOuter Membrane Proteins
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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Total synthesis of escherichia coli lipid A
Masahiro Imoto, Hiroyuki Yoshimura, Nobuki Sakaguchi et al. · Tetrahedron Letters · 1985 · 179 citations