Peptide stabilized amphotericin B nanodisks

Peptides. 2007 Apr;28(4):741-6. doi: 10.1016/j.peptides.2007.01.007. Epub 2007 Jan 19.


Nanometer scale apolipoprotein A-I stabilized phospholipid disk complexes (nanodisks; ND) have been formulated with the polyene antibiotic amphotericin B (AMB). The present studies were designed to evaluate if a peptide can substitute for the function of the apolipoprotein component of ND with respect to particle formation and stability. An 18-residue synthetic amphipathic alpha-helical peptide, termed 4F (Ac-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-NH(2)), solubilized vesicles comprised of egg phosphatidylcholine (egg PC), dipentadecanoyl PC or dimyristoylphosphatidylcholine (DMPC) at rates greater than or equal to solubilization rates observed with human apolipoprotein A-I (apoA-I; 243 amino acids). Characterization studies revealed that interaction with DMPC induced a near doubling of 4F tryptophan fluorescence emission quantum yield (excitation 280 nm) and a approximately 7 nm blue shift in emission wavelength maximum. Inclusion of AMB in the vesicle substrate resulted in formation of 4F AMB-ND. Spectra of AMB containing particles revealed the antibiotic is a highly effective quencher of 4F tryptophan fluorescence emission, giving rise to a Ksv=7.7 x 10(4). Negative stain electron microscopy revealed that AMB-ND prepared with 4F possessed a disk shaped morphology similar to ND prepared without AMB or prepared with apoA-I. In yeast and pathogenic fungi growth inhibition assays, 4F AMB-ND was as effective as apoA-I AMB-ND. The data indicate that AMB-ND generated using an amphipathic peptide in lieu of apoA-I form a discrete population of particles that possess potent biological activity. Given their intrinsic versatility, peptides may be preferred for scale up and clinical application of AMB-ND.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amphotericin B / chemistry*
  • Amphotericin B / pharmacology
  • Antifungal Agents / chemistry*
  • Antifungal Agents / pharmacology
  • Apolipoprotein A-I / chemistry
  • Apolipoprotein A-I / pharmacology
  • Aspergillus fumigatus / drug effects
  • Aspergillus fumigatus / growth & development
  • Candida albicans / drug effects
  • Candida albicans / growth & development
  • Cryptococcus neoformans / drug effects
  • Cryptococcus neoformans / growth & development
  • Microscopy, Electron, Transmission
  • Models, Chemical
  • Molecular Sequence Data
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Nanotechnology
  • Peptides / chemistry*
  • Peptides / pharmacology
  • Phospholipids / chemistry
  • Spectrometry, Fluorescence


  • Antifungal Agents
  • Apolipoprotein A-I
  • Peptides
  • Phospholipids
  • Amphotericin B