title: Hairpin structure stability plays a role in the activity of two antimicrobial peptides.
abstract: Many naturally occurring antimicrobial peptides (AMPs) are amphipathic with a β-hairpin conformation stabilized by cross-strand disulfides across the associated β-strands. Here, we show that the disulfides are not essential. Other structuring means such as better β-turns and noncovalent cross-strand interactions can, with proper design, replace the disulfides with no loss in antimicrobial activity. Our results also demonstrate that the hairpin turn region may play a role in membrane recognition for at least one member of this class, since a homodimeric turnless β-sheet analog showed no antimicrobial activity. We also examined the effects of N-terminal fatty acid adducts on AMPs. Surprisingly, the large hydrophobic carboxylic moieties examined completely eliminated the antimicrobial activity of previously active β-hairpin peptides.
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA, USA.
authors.forename: Kalkena
authors.initials: K
authors.lastname: Sivanesam
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA, USA.
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Kier
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA, USA.
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Whedon
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA, USA.
authors.forename: Champak
authors.initials: C
authors.lastname: Chatterjee
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA, USA.
authors.forename: Niels H
authors.initials: NH
authors.lastname: Andersen
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D048230:Corynebacterium glutamicum / Q000187:drug effects / Q000254:growth & development; D004268:DNA-Binding Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004220:Disulfides / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D055550:Protein Stability; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D004220:Disulfides; D010456:Peptides, Cyclic; C415987:gomesin; C057636:tachyplesin peptide, Tachypleus tridentatus
keywords: antimicrobial; gomesin; hairpin peptides; tachyplesin