Total synthesis of Septocylindrin B and C-terminus modified analogues

PLoS One. 2012;7(12):e51708. doi: 10.1371/journal.pone.0051708. Epub 2012 Dec 20.

Abstract

The total synthesis is reported of the peptaibol Septocylindrin B which is related to the well documented channel forming peptaibol antibiotic Alamethicin. Several analogues were synthesized with a modified C-terminus, to investigate the SAR of the terminal residue Phaol. All these peptides were tested for their membrane perturbation properties by fluorescent dye leakage assay and for their antibacterial activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alamethicin / analogs & derivatives*
  • Alamethicin / chemical synthesis
  • Alamethicin / pharmacology
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Cell Membrane / drug effects
  • Chromatography, High Pressure Liquid
  • Magnetic Resonance Spectroscopy
  • Peptaibols / chemical synthesis*
  • Peptaibols / pharmacology
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Peptaibols
  • septocylindrin B
  • Alamethicin

Grants and funding

JN thanks the Institute for the Promotion of Innovation through Science and Technology in Flanders (Belgium, I.W.T., www.iwt.be) for financial support. KN thanks KU Leuven for financial support (Project OT/11/047/TBA). CL is supported by the IOF Knowledge Platform grant (“Functional peptidomics” IOF/KP/09/003) of the KU Leuven. This work was also partly supported by a grant of the FWO Vlaanderen (G.0599.11). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.