Peptide stabilized amphotericin B nanodisks

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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

Fingerprint

Amphotericin B
Peptides
Apolipoprotein A-I
Dimyristoylphosphatidylcholine
Tryptophan
Fluorescence
Anti-Bacterial Agents
Polyenes
Apolipoproteins
Quantum yield
Bioactivity
Fungi
Phosphatidylcholines
Yeast
Electron microscopy
Ovum
Assays
Phospholipids
Electron Microscopy
Coloring Agents

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

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

Peptide stabilized amphotericin B nanodisks. / Tufteland, Megan; Pesavento, Joseph B.; Bermingham, Rachelle L.; Hoeprich, Paul D.; Ryan, Robert O.

In: Peptides, Vol. 28, No. 4, 04.2007, p. 741-746.

Research output: Contribution to journalArticle

Tufteland, M, Pesavento, JB, Bermingham, RL, Hoeprich, PD & Ryan, RO 2007, 'Peptide stabilized amphotericin B nanodisks', Peptides, vol. 28, no. 4, pp. 741-746. https://doi.org/10.1016/j.peptides.2007.01.007
Tufteland M, Pesavento JB, Bermingham RL, Hoeprich PD, Ryan RO. Peptide stabilized amphotericin B nanodisks. Peptides. 2007 Apr;28(4):741-746. https://doi.org/10.1016/j.peptides.2007.01.007
Tufteland, Megan ; Pesavento, Joseph B. ; Bermingham, Rachelle L. ; Hoeprich, Paul D. ; Ryan, Robert O. / Peptide stabilized amphotericin B nanodisks. In: Peptides. 2007 ; Vol. 28, No. 4. pp. 741-746.
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AB - 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.

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