Interactions of a designed peptide with lipopolysaccharide: Bound conformation and anti-endotoxic activity

Anirban Bhunia, Geok Lin Chua, Prerna N. Domadia, Hemamali Warshakoon, Jens R. Cromer, Sunil A. David, Surajit Bhattacharjya

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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, H2N-YVKLWRMIKFIR-CONH2 (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.

Original languageEnglish (US)
Pages (from-to)853-857
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume369
Issue number3
DOIs
StatePublished - May 9 2008

Bibliographical note

Funding Information:
This work is supported by a research Grant, No. 06/1/22/19/446, from A∗Star BMRC Singapore. The atomic coordinates of an ensemble of LPS bound structures and chemical shifts of YW12D are deposited to BioMagResBank (Accession Code: 15413).

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

  • Drug design
  • Endotoxin
  • LPS
  • Lipopolysaccharide
  • NMR
  • Peptide design
  • Sepsis
  • Transferred nuclear Overhauser effect
  • tr-NOESY

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