Please use this identifier to cite or link to this item:
|Title:||Rupture of Lipid Vesicles by a Broad-Spectrum Antiviral Peptide: Influence of Vesicle Size||Authors:||Zan, Goh Haw
Zhdanov, Vladimir P.
Jackman, Joshua Alexander
|Keywords:||Materials Science and Engineering
Chemical and Biomedical Engineering
|Issue Date:||2013||Source:||Jackman, J. A., Zan, G. H., Zhdanov, V. P., & Cho, N.-J. (2013). Rupture of Lipid Vesicles by a Broad-Spectrum Antiviral Peptide: Influence of Vesicle Size. The Journal of Physical Chemistry B, 117(50), 16117-16128.||Series/Report no.:||The Journal of Physical Chemistry B||Abstract:||An amphipathic α-helical (AH) peptide was recently discovered that can rupture the lipid envelope of many viruses including HIV, hepatitis C, dengue, and herpes simplex. Despite its broad-spectrum activity, the AH peptide specifically targets small viruses only and does not affect large viruses. Indirect observations of virus size-specific targeting have been confirmed in a model system comprised of intact lipid vesicles on a gold substrate. Depending on vesicle size, AH peptide can promote vesicle rupture, but the mechanism by which vesicle size influences the rupture process remains to be elucidated. Herein, using the dynamic light scattering and quartz crystal microbalance with dissipation techniques, we have combined experiment and theory to understand the effects of vesicle size on the interaction between the AH peptide and vesicles. We identified that the AH peptide-binding interaction can induce a structural rearrangement of the vesicle’s lipid bilayer, which occurs independently of vesicle size. Kinetic analysis also revealed that AH peptide-binding occurs cooperatively for small vesicles only. Binding cooperativity is consistent with pore formation leading to vesicle rupture. By contrast, for large vesicles, AH peptide-binding is noncooperative and does not cause vesicle rupture, suggesting that the binding interaction occurs via a different mechanism. Compared to previous estimates that AH peptide is most effective against viruses with a diameter of less than 70 nm, our evidence validates that AH peptide may target a wider size range of enveloped viruses up to 160 nm in diameter. Taken together, our findings provide a quantitative rationale to understand the targeting specificity of AH peptide as a broad-spectrum antiviral drug candidate.||URI:||https://hdl.handle.net/10356/81034
|ISSN:||1520-6106||DOI:||http://dx.doi.org/10.1021/jp409716p||Rights:||© 2013 American Chemical Society||Fulltext Permission:||none||Fulltext Availability:||No Fulltext|
|Appears in Collections:||MSE Journal Articles|
SCBE Journal Articles
Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.