title: Interactions of a designed peptide with lipopolysaccharide: Bound conformation and anti-endotoxic activity.
abstract: Designed peptides that would selectively interact with lipopolysaccharide (LPS) or endotoxin and fold into specific conformations could serve as important scaffolds toward the development of antisepsis compounds. Here, we describe solution structure of a designed amphipathic peptide, H(2)N-YVKLWRMIKFIR-CONH(2) (YW12D) in complex with endotoxin as determined by transferred nuclear Overhauser effect spectroscopy. The conformation of the isolated peptide is highly flexible, but undergoes a dramatic structural stabilization in the presence of LPS. Structure calculations reveal that the peptide presents two amphipathic surfaces in its bound state to LPS whereby each surface is characterized by two positive charges and a number of aromatic and/or aliphatic residues. ITC data suggests that peptide interacts with two molecules of lipid A. In activity assays, YW12D exhibits neutralization of LPS toxicity with very little hemolysis of red blood cells. Structural and functional properties of YW12D would be applicable in designing low molecular weight non-toxic antisepsis molecules.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Anirban
authors.initials: A
authors.lastname: Bhunia
authors.forename: Geok Lin
authors.initials: GL
authors.lastname: Chua
authors.forename: Prerna N
authors.initials: PN
authors.lastname: Domadia
authors.forename: Hemamali
authors.initials: H
authors.lastname: Warshakoon
authors.forename: Jens R
authors.initials: JR
authors.lastname: Cromer
authors.forename: Sunil A
authors.initials: SA
authors.lastname: David
authors.forename: Surajit
authors.initials: S
authors.lastname: Bhattacharjya
mesh_terms: D002460:Cell Line; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D021381:Protein Transport
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D009842:Oligopeptides; C528174:YW12d peptide