Peptide stabilized amphotericin B nanodisks

Megan Tufteland, Joseph B. Pesavento, Rachelle L. Bermingham, Paul D. Hoeprich, Robert O. Ryan

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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 α-helical peptide, termed 4F (Ac-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-NH2), 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 ∼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 × 104. 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.

Original languageEnglish (US)
Pages (from-to)741-746
Number of pages6
JournalPeptides
Volume28
Issue number4
DOIs
StatePublished - Apr 2007
Externally publishedYes

Keywords

  • Amphotericin B
  • Apolipoprotein A-I
  • Dimyristoylphosphatidylcholine
  • Electron microscopy
  • Nanodisk
  • Peptide

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Tufteland, M., Pesavento, J. B., Bermingham, R. L., Hoeprich, P. D., & Ryan, R. O. (2007). Peptide stabilized amphotericin B nanodisks. Peptides, 28(4), 741-746. https://doi.org/10.1016/j.peptides.2007.01.007