The Sushi peptides: structural characterization and mode of action against Gram-negative bacteria |
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Authors: | J L Ding P Li B Ho |
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Institution: | (1) Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore, 117543, Singapore;(2) Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore, 117597, Singapore;(3) Present address: Singapore Immunology Network, A*StAR, Biopolis, 138688, Singapore |
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Abstract: | The compositional difference in microbial and human cell membranes allows antimicrobial peptides to preferentially bind microbes.
Peptides which specifically target lipopolysaccharide (LPS) and palmitoyl-oleoyl-phosphatidylglycerol (POPG) are efficient
antibiotics. From the core LPS-binding region of Factor C, two 34-mer Sushi peptides, S1 and S3, were derived. S1 functions
as a monomer, while S3 is active as a dimer. Both S1 and S3 display detergent-like properties in disrupting LPS aggregates,
with specificity for POPG resulting from electrostatic and hydrophobic forces between the peptides and the bacterial lipids.
During interaction with POPG, the S1 transitioned from a random coil to an α-helix, while S3 resumed a mixture of α-helix
and β-sheet structures. The unsaturated nature of POPG confers fluidity and enhances insertion of the peptides into the lipid
bilayer, causing maximal disruption of the bacterial membrane. These parameters should be considered in designing and developing
new generations of peptide antibiotics with LPS-neutralizing capability.
Received 2 October 2007; received after revision 2 November 2007; accepted 4 December 2007
J. L. Ding, B. Ho: Co-senior authors. |
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Keywords: | Synthetic antimicrobial peptides Sushi peptides LPS-binding and disruption membrane phospholipids |
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