title: The Sushi peptides: structural characterization and mode of action against Gram-negative bacteria.
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 alpha-helix, while S3 resumed a mixture of alpha-helix and beta-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.
authors.affiliation: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore. dbsdjl@nus.edu.sg
authors.forename: J L
authors.initials: JL
authors.lastname: Ding
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: B
authors.initials: B
authors.lastname: Ho
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D010455:Peptides; D010743:Phospholipids