title: Synthesis, preferred conformation, protease stability, and membrane activity of heptaibin, a medium-length peptaibiotic.
abstract: The medium-length peptaibiotics are characterized by a primary structure of 14-16 amino acid residues. Despite the interesting antibiotic and antifungal properties exhibited by these membrane-active peptides, their exact mechanism of action is still unknown. Here, we present our results on heptaibin, a 14-amino acid peptaibiotic found to exhibit antimicrobial activity against Staphylococcus aureus. We carried out the very challenging synthesis of heptaibin on solid phase and a detailed conformational analysis in solution. The peptaibiotic is folded in a mixed 3₁₀-/α-helix conformation which exhibits a remarkable amphiphilic character. We also find that it is highly stable toward degradation by proteolytic enzymes and nonhemolytic. Finally, fluorescence leakage experiments using small unilamellar vesicles of three different compositions revealed that heptaibin, although uncharged, is a selective compound for permeabilization of model membranes mimicking the overall negatively charged surface of Gram-positive bacteria. This latter finding is in agreement with the originally published antimicrobial activity data.
authors.affiliation: ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, via Marzolo 1, 35131 Padova, Italy. marta.dezotti@unipd.it
authors.forename: Marta
authors.initials: M
authors.lastname: De Zotti
authors.forename: Barbara
authors.initials: B
authors.lastname: Biondi
authors.forename: Cristina
authors.initials: C
authors.lastname: Peggion
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Park
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Hahm
authors.forename: Fernando
authors.initials: F
authors.lastname: Formaggio
authors.forename: Claudio
authors.initials: C
authors.lastname: Toniolo
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D004795:Enzyme Stability / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D009842:Oligopeptides; C414189:heptaibin; D010447:Peptide Hydrolases