Employing an Amphipathic Viral Peptide to Create a Lipid Bilayer on Au and TiO<sub>2</sub>

Cho, Nam‐Joon; Cho, Sang-Joon; Cheong, Kwang Ho; Glenn, Jeffrey S.; Frank, Curtis W.

doi:10.1021/ja0701412

Cited by 111 publications

(164 citation statements)

References 18 publications

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“…Second, proteinaceous components may modulate the properties of the lipid membrane itself, thus affecting the binding interaction of the AH peptide to lipid and/or other protein biologically relevant for studying macromolecular interaction kinetics. Recent studies have investigated how AH peptide affects the film properties of the intact vesicle platform [40,42]. With the collection of characterization data, there is an increasing amount of information about the molecular determinants of the target interaction.…”

Section: Fundamental Characterization Of Model Biological Systemmentioning

confidence: 99%

“…In this outlook, we introduce areas where we envision engineering strategies may further aid antiviral drug development. By assembling an in situ assay to predict virus particle rupture [40][41][42][43], the work reviewed here has established a cost-effective tool to rapidly screen and functionally characterize antiviral drug candidates in minutes rather than days. Based on this preliminary format, the system can be improved by increasing sensitivity to reduce the amount of peptide material required and/or adapting the signal response to a more readily high-throughput measurement technique.…”

Section: Outlook On Engineering Strategies For Antiviral Drug Developmentioning

confidence: 99%

“…As a case study example of a viral pathogen target, we have selected the hepatitis C virus (HCV) and discuss how engineering strategies identified a previously unknown functional activity encoded within the HCV nonstructural 5A (NS5A) protein. By employing a model membrane platform to mimic the host cell membrane interface upon which viral genome replication occurs, a striking ability to lyse lipid vesicles was discovered within the NS5A N-terminal amphipathic, a-helix (AH) [40][41][42][43].…”

Section: Introductionmentioning

confidence: 99%

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Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

Jackman

Cho

2012

Biointerphases

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As one of the most important interfaces in cellular systems, biological membranes have essential functions in many activities such as cellular protection and signaling. Beyond their direct functions, they also serve as scaffolds to support the association of proteins involved in structural support, adhesion, and transport. Unfortunately, biological processes sometimes malfunction and require therapeutic intervention. For those processes which occur within or upon membranes, it is oftentimes difficult to study the mechanism in a biologically relevant, membranous environment. Therefore, the identification of direct therapeutic targets is challenging. In order to overcome this barrier, engineering strategies offer a new approach to interrogate biological activities at membrane interfaces by analyzing them through the principles of the interfacial sciences. Since membranes are complex biological interfaces, the development of simplified model systems which mimic important properties of membranes can enable fundamental characterization of interaction parameters for such processes. We have selected the hepatitis C virus (HCV) as a model viral pathogen to demonstrate how model membrane platforms can aid antiviral drug discovery and development. Responsible for generating the genomic diversity that makes treating HCV infection so difficult, viral replication represents an ideal step in the virus life cycle for therapeutic intervention. To target HCV genome replication, the interaction of viral proteins with model membrane platforms has served as a useful strategy for target identification and characterization. In this review article, we demonstrate how engineering approaches have led to the discovery of a new functional activity encoded within the HCV nonstructural 5A protein. Specifically, its N-terminal amphipathic, α-helix (AH) can rupture lipid vesicles in a size-dependent manner. While this activity has a number of exciting biotechnology and biomedical applications, arguably the most promising one is in antiviral medicine. Based on the similarities between lipid vesicles and the lipid envelopes of virus particles, experimental findings from model membrane platforms led to the prediction that a range of medically important viruses might be susceptible to rupturing treatment with synthetic AH peptide. This hypothesis was tested and validated by molecular virology studies. Broad-spectrum antiviral activity of the AH peptide has been identified against HCV, HIV, herpes simplex virus, and dengue virus, and many more deadly pathogens. As a result, the AH peptide is the first in class of broad-spectrum, lipid envelope-rupturing antiviral agents, and has entered the drug pipeline. In summary, engineering strategies break down complex biological systems into simplified biomimetic models that recapitulate the most important parameters. This approach is particularly advantageous for membrane-associated biological processes because model membrane platforms provide more direct characterization of target interactions than is possible with other methods. Consequently, model membrane platforms hold great promise for solving important biomedical problems and speeding up the translation of biological knowledge into clinical applications.

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Section: Fundamental Characterization Of Model Biological Systemmentioning

confidence: 99%

Section: Outlook On Engineering Strategies For Antiviral Drug Developmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

Jackman

Cho

2012

Biointerphases

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“…[12][13][14] Recently, Shiraki group suggested a simple test method for adsorption and disruption of lipid bilayers by nanoscale protein aggregation.…”

Section: 11mentioning

confidence: 99%

Simple Analysis for Interaction between Nanoparticles and Dye-Containing Vesicles as a Biomimetic Cell-Membrane

Shin

Umh²,

Kim³

2013

Bulletin of the Korean Chemical Society

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Some cytotoxicity studies for the interpretation of the interaction between nanoparticles and cells are nonmechanistic and time-consuming. Therefore, non-biological screening methods, which are faster and simpler than in-vivo and in-vitro methods, are required as alternatives to current cytotoxicity tests. Here, we proposed a simple screening method for the analysis of the interaction between several AgNPs (bare-, citrate-, and polyvinylpyrrolidone-coating) and dye-containing vesicles acting as a biomimetic cell-membrane. The interaction between AgNPs and vesicles could be evaluated readily by UV-vis spectra. Absorbance deviation in UV-vis spectra revealed a large attraction between neighboring particles and vesicles. This was confirmed by (Derjagin, Landau, Verwey, and Overbeek) theory and DMF (dark-field microscopy) analysis. This proposed method might be useful for analyzing the cytotoxicity of nanoparticles with cell-membranes instead of in vitro or in vivo cytotoxicity tests.

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“…As shown in Scheme 1(a), PC consists of a long double carbon chain, and the zwitterions pair headgroup is composed of phosphate and choline. Phospholipids have been adsorbed on various matrixes [22][23][24][25][26], Scheme 1. Diagrams of (a) the chemical structure of PC and (b) supported lipid bilayers on magnetic nanoparticle for target analytes adsorption.…”

Section: Introductionmentioning

confidence: 99%

Biocompatible phosphatidylcholine bilayer coated on magnetic nanoparticles and their application in the extraction of several polycyclic aromatic hydrocarbons from environmental water and milk samples

Zhang

Niu

Zhang

et al. 2012

Journal of Chromatography A

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Employing an Amphipathic Viral Peptide to Create a Lipid Bilayer on Au and TiO₂

Cited by 111 publications

References 18 publications

Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

Simple Analysis for Interaction between Nanoparticles and Dye-Containing Vesicles as a Biomimetic Cell-Membrane

Biocompatible phosphatidylcholine bilayer coated on magnetic nanoparticles and their application in the extraction of several polycyclic aromatic hydrocarbons from environmental water and milk samples

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Employing an Amphipathic Viral Peptide to Create a Lipid Bilayer on Au and TiO2

Cited by 111 publications

References 18 publications

Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

Simple Analysis for Interaction between Nanoparticles and Dye-Containing Vesicles as a Biomimetic Cell-Membrane

Biocompatible phosphatidylcholine bilayer coated on magnetic nanoparticles and their application in the extraction of several polycyclic aromatic hydrocarbons from environmental water and milk samples

Contact Info

Product

Resources

About

Employing an Amphipathic Viral Peptide to Create a Lipid Bilayer on Au and TiO₂