Sunil, A David and Satish, K Awasthi and Balaram, P (2000) The role of polar and facial amphipathic character in determining lipopolysaccharide-binding properties in synthetic cationic peptides. In: Journal of Endotoxin Research, 6 (3). pp. 249-256.
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Two series of peptides, designated K and NK were synthesized and tested for lipid A binding and neutralizing properties. K-2, which has an 11-residue amphiphilic core, and a branched N-terminus bearing two branched lysinyl residues does not bind lipid A, while NK2, also with an 11-residue amphiphilic core comprised entirely of non-ionizable residues, and a similarly branched, cationic N-terminus, binds lipid A very weakly. Both peptides do not inhibit lipopolysaccharide (LPS) activity in the Limulus assay, nor do they inhibit LPS-induced TNF-alpha and NO production in 5774 cells. These results are entirely unlike a homologous peptide with an exclusively hydrophobic core whose LPS-binding and neutralizing properties are very similar to that of polymyxin B [David SA, Awasthi SK, Wiese A et al. Characterization of the interactions of a polycationic, amphiphilic, terminally branched oligopeptide with lipid A and lipopolysaccharide from the deep rough mutant of Salmonella minnesota. J Endotoxin Res 1996; 3: 369-379]. These data suggest that a clear segregation of charged and apolar domains is crucial in molecules designed for purposes of LPS sequestration and that head-tail (polar) orientation of the cationic/hydrophobic regions is preferable to molecules with mixed or facial cationic/amphipathic character.
|Item Type:||Journal Article|
|Additional Information:||Copy right of this article belongs to Sage Publications.|
|Department/Centre:||Division of Biological Sciences > Molecular Biophysics Unit|
|Date Deposited:||30 Apr 2010 04:55|
|Last Modified:||19 Sep 2010 06:01|
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