Structure of a Synthetic Fragment of the LALF Protein When Bound to Lipopolysaccharide

• Published in: Journal of medicinal chemistry Vol. 48; no. 5; pp. 1666 - 1670
• Main Authors: PRISTOVSEK, Primoz, FEHER, Krisztina, SZILAGYI, Laszlo, KIDRIC, Jurka
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 10.03.2005
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimicrobial Cationic Peptides; Antiseptics; Arthropod Proteins; Biological and medical sciences; Invertebrate Hormones - chemistry; Lipopolysaccharides - chemistry; Magnetic Resonance Spectroscopy; Medical sciences; Miscellaneous; Models, Molecular; Peptide Fragments - chemistry; Peptides, Cyclic - chemistry; Pharmacology. Drug treatments; Protein Binding; Solutions; Water; Cyclic peptides; Overhauser effect; NMR spectrometry; Endotoxin; Modeling; Protein; Toxic shock syndrome; Infection; Toxin; Structure activity relation; Peptide fragment; Sulfur peptide; Antiseptic; Molecular model; Bacteriosis; Lipopolysaccharide; Staphylococcal infection; Conjugated compound; Antilipopolysaccharide factor
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm049217k

Peptidic lipopolysaccharide (LPS) antagonists are the subject of intensive research. We report an NMR and modeling study of LALF-14 (GCKPTFRRLKWKYKCG), a synthetic cyclized fragment of the limulus anti-LPS factor (LALF) comprising residues 36−47. In a mixture with LPS we observed the transferred NOE effect and derived the LPS-bound structure of LALF-14. Neither the free nor the LPS-bound peptide displays NOEs indicative of a β-sheet-like structure that is adopted by the fragment in the full-size protein. However, docking calculations show that the former structure is not a prerequisite for binding of LALF-14 to LPS.