Lipopolysaccharide (LPS) neutralizing peptides reveal a lipid A binding site of LPS binding protein.
Endotoxic shock follows a cascade of events initiated by release of lipopolysaccharide during infection with Gram-negative organisms. Two overlapping 15-mer peptides were identified, corresponding to residues 91-108 of human lipopolysaccharide binding protein that specifically bound the lipid A moiety of lipopolysaccharide with high affinity. The peptides inhibited binding of lipopolysaccharide to lipopolysaccharide binding protein, inhibited the chromogenic Limulus amebocyte lysate reaction, and blocked release of tumor necrosis factor alpha following lipopolysaccharide challenge both in vitro and in vivo. These results suggest lipopolysaccharide binding protein residues 91-108 form at least part of the lipopolysaccharide binding site. Moreover, derivatives of lipopolysaccharide binding protein residues 91-108 might modulate lipopolysaccharide toxicity in the clinical setting.
Taylor
A H
AH
Department of Pharmaceutical Research, Centocor, Inc., Malvern, Pennsylvania 19355-1307, USA.
Heavner
G
G
Nedelman
M
M
Sherris
D
D
Brunt
E
E
Knight
D
D
Ghrayeb
J
J
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008050:Lipid A / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D008050:Lipid A; D008562:Membrane Glycoproteins; D010455:Peptides; D000099231:Lipopolysaccharide-Binding Protein