Synthesis, preferred conformation, protease stability, and membrane activity of heptaibin, a medium-length peptaibiotic
Version of Record online: 14 APR 2011
Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Volume 17, Issue 8, pages 585–594, August 2011
How to Cite
De Zotti, M., Biondi, B., Peggion, C., Park, Y., Hahm, K.-S., Formaggio, F. and Toniolo, C. (2011), Synthesis, preferred conformation, protease stability, and membrane activity of heptaibin, a medium-length peptaibiotic. J. Peptide Sci., 17: 585–594. doi: 10.1002/psc.1364
- Issue online: 15 JUL 2011
- Version of Record online: 14 APR 2011
- Manuscript Accepted: 18 JAN 2011
- Manuscript Received: 11 JAN 2011
- Italian Ministry of University and Research
- α-aminoisobutyric acid;
- helical structure;
- membrane activity;
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. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.