Structure of a Synthetic Fragment of the Lipopolysaccharide (LPS) Binding Protein When Bound to LPS and Design of a Peptidic LPS Inhibitor

Peptidic lipopolysaccharide (LPS) antagonists are the subject of intensive research. We report an NMR and modeling study of LBP-14 (RVQGRWKVRASFFK), a synthetic fragment of the LPS binding protein (LBP). In a mixture with LPS we observed the transferred nuclear Overhauser effect and determined the L...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2005-12, Vol.48 (24), p.7911-7914
Main Authors: Pristovšek, Primož, Simčič, Saša, Wraber, Branka, Urleb, Uroš
Format: Article
Language:English
Subjects:
Acute-Phase Proteins - chemistry
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Carrier Proteins - chemistry
Cells, Cultured
General aspects
Humans
Leukocytes, Mononuclear - drug effects
Leukocytes, Mononuclear - metabolism
Lipopolysaccharides - antagonists & inhibitors
Lipopolysaccharides - pharmacology
Magnetic Resonance Spectroscopy
Medical sciences
Membrane Glycoproteins - chemistry
Models, Molecular
Molecular Structure
Peptide Fragments - chemical synthesis
Peptide Fragments - chemistry
Peptide Fragments - pharmacology
Pharmacology. Drug treatments
Tumor Necrosis Factor-alpha - metabolism
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Summary:Peptidic lipopolysaccharide (LPS) antagonists are the subject of intensive research. We report an NMR and modeling study of LBP-14 (RVQGRWKVRASFFK), a synthetic fragment of the LPS binding protein (LBP). In a mixture with LPS we observed the transferred nuclear Overhauser effect and determined the LPS-bound structure of LBP-14 that was used for docking calculations to LPS. The derived complex was used to design a peptide that displayed more than 50% increase in LPS inhibition in vitro.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm050762a