Virus replication inhibitory peptide inhibits the conversion of phospholipid bilayers to the hexagonal phase

1986 ◽  
Vol 6 (7) ◽  
pp. 647-653 ◽  
Author(s):  
Richard M. Epand
Keyword(s):  
Phase Transition ◽  
Transition Temperature ◽  
Viral Replication ◽  
Membrane Fusion ◽  
Phase Transition Temperature ◽  
Virus Replication ◽  
Hexagonal Phase ◽  
Specific Inhibitor ◽  
Viral Glycoprotein ◽  
Inhibitory Peptide

Virus replication inhibitory peptide (carbobenzoxy-D-Phe-L-PheGly) was shown to be a potent specific inhibitor of the replication of paramyxovirus and myxovirus (Richardson, Scheid and Choppin (1980), Virology105, 205–222). This peptide inhibits the membrane fusing activity of a viral glycoprotein. Many agents which promote the formation of the hexagonal phase in membranes also accelerate membrane fusion. At a mole fraction of 0.1, viral replication inhibitory peptide can raise the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine by almost 10°. Two related peptides, carbobenzoxy-L-PheGly and carbobenzoxy-L-GlyPhe, are less potent in raising the bilayer to hexagonal phase transition temperature, with the latter peptide being the least effective of the three. This order of potency is the same as the order of potency in inhibiting viral replication. Substances which inhibit hexagonal phase formation of pure lipids may also inhibit membrane fusion.

Bilayer stabilizing peptides and the inhibition of viral infection: antimeasles activity of carbobenzoxy-Ser-Leu-amide

1987 ◽  
Vol 7 (9) ◽  
pp. 745-749 ◽  
Author(s):  
Richard M. Epand ◽  
Thomas J. Lobl ◽  
H. E. Renis
Keyword(s):  
Phase Transition ◽  
Transition Temperature ◽  
Phase Transition Temperature ◽  
Measles Virus ◽  
Cytopathic Effect ◽  
Hexagonal Phase ◽  
Vero Cells ◽  
Time Parameter ◽  
Scanning Calorimetry ◽  
Hplc Retention Time

A number of carbobenzoxy-dipeptide-amides raise the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine (stabilizes the bilayer). The potency of the peptides in stabilizing the bilayer phase is Z-Tyr-Leu-NH2>Z-Gly-Phe-NH2>Z-Ser-Leu-NH2>Z-Gly-Leu-NH2>Z-Gly-Gly-NH2. A linear correlation was found between the respective HPLC retention time parameter k′ for the peptide and the slope of the bilayer stabilization curve determined with model membranes by differential scanning calorimetry. One dipeptide, Z-Ser-Leu-NH2, reduces measles virus cytopathic effect (CPE) in Vero cells. The mechanism by which this peptide reduces the CPE is not known, although some peptides which raise the bilayer to hexagonal phase transition temperature of phospholipids inhibit membrane fusion.

Comparison of the interaction of the anti-viral chemotherapeutic agents amantadine and tromantadine with model phospholipid membranes

1987 ◽  
Vol 7 (3) ◽  
pp. 225-230 ◽  
Author(s):  
James J. Cheetham ◽  
Richard M. Epand
Keyword(s):  
Phase Transition ◽  
Plasma Membrane ◽  
Transition Temperature ◽  
Cyclosporin A ◽  
Membrane Fusion ◽  
Cell Fusion ◽  
Viral Infections ◽  
Hexagonal Phase ◽  
Chemotherapeutic Agents ◽  
Hydrophilic Group

Amantadine and tromantadine are agents used against influenza and herpes infections, respectively. Tromantadine raises the bilayer to hexagonal phase transition temperature of synthetic phosphatidylethanolamines and is less disruptive to phospholipid packing. Tromantadine acts similar to cyclosporin A, previously demonstrated to inhibit viral-induced cell-cell fusion. We suggest the balance between the hydrophobic and hydrophilic group sizes would allow tromantadine to prevent membrane fusion more than amantadine and thus inhibit infection by viruses such as Herpes, which fuse with the plasma membrane. Study of agents which stabilize the bilayer phase of membranes may lead to efficacious inhibitors of viral infections requiring cell fusion events.

The relationship between the bilayer to hexagonal phase transition temperature in membranes and protein kinase C activity

1988 ◽  
Vol 8 (1) ◽  
pp. 49-54 ◽  
Author(s):  
Richard M. Epand ◽  
Alan R. Stafford ◽  
James J. Cheetham ◽  
Remo Bottega ◽  
Eric H. Ball
Keyword(s):  
Phase Transition ◽  
Protein Kinase C ◽  
Transition Temperature ◽  
Protein Kinase ◽  
Phase Transition Temperature ◽  
Hexagonal Phase ◽  
Protein Kinase C Inhibitors ◽  
Kinase C ◽  
Protein Kinase C Activity ◽  
Protein Kinase C Activators

A number of substances affect the activity of protein kinase C. Among uncharged and zwitterionic compounds, those which activate protein kinase C also lower the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine while substances which inhibit protein kinase C raise this transition temperature. Using this criteria, we have identified 3β-chloro-5-cholestene, 5β-cholan-24-ol and eicosane as new protein kinase C activators and have shown that Z-Ser-Leu-NH2, Z-Gly-Leu-NH2, Z-Tyr-Leu-NH2, cyclosporin A and cholestan-3β, 5α, 6β-triol are protein kinase C inhibitors.

Evidence for the regulation of the activity of protein kinase C through changes in membrane properties

1991 ◽  
Vol 11 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Richard M. Epand ◽  
Raquel F. Epand ◽  
Bryan T.-C. Leon ◽  
Fredric M. Menger ◽  
J. F. Kuo
Keyword(s):  
Phase Transition ◽  
Protein Kinase C ◽  
Transition Temperature ◽  
Protein Kinase ◽  
Phase Transition Temperature ◽  
Hexagonal Phase ◽  
Lipid Phase ◽  
Kinase C ◽  
Protein Kinase C Activity ◽  
Lipid Polymorphism

We measured the effects of two branched-chain analogs of distearoyl-phosphatidylcholine, containing either a methyl or an n-butyl group at the 8 position, on the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine. The former compound raised the bilayer to hexagonal phase transition temperature while the latter compound lowered it. The opposite effects of these amphiphiles on protein kinase C activity (inhibition and activation, respectively) correlated with their effects on lipid polymorphism. Because of the similarity of the structures of these two compounds, it seems likely that their opposite effects on the activity of protein kinase C is a result of their alteration of the lipid environment of the membrane rather than to binding to a specific site on the protein. We also compared the effects of hexachlorophene on lipid polymorphism and protein kinase C activity at high and at low calcium concentrations. We also found that the effect of hexachlorophene forming a complex with Ca2+ is to increase both the hexagonal phase forming propensity of the membrane as well as to increase the activity of protein kinase C, again demonstrating the correlation between lipid phase propensity and effects on protein kinase C activity.

The structure of membranes and membrane proteins embedded in amorphous ice

1992 ◽  
Vol 50 (1) ◽  
pp. 432-433
Author(s):  
Uwe Lücken ◽  
Joachim Jäger
Keyword(s):  
Phase Transition ◽  
Transition Temperature ◽  
Membrane Proteins ◽  
Phase Transition Temperature ◽  
Lipid Vesicles ◽  
Freezing Stress ◽  
Amorphous Ice ◽  
Different Temperatures ◽  
Band Pass ◽  
Lipid Polymorphism

TEM imaging of frozen-hydrated lipid vesicles has been done by several groups Thermotrophic and lyotrophic polymorphism has been reported. By using image processing, computer simulation and tilt experiments, we tried to learn about the influence of freezing-stress and defocus artifacts on the lipid polymorphism and fine structure of the bilayer profile. We show integrated membrane proteins do modulate the bilayer structure and the morphology of the vesicles.Phase transitions of DMPC vesicles were visualized after freezing under equilibrium conditions at different temperatures in a controlled-environment vitrification system. Below the main phase transition temperature of 24°C (Fig. 1), vesicles show a facetted appearance due to the quasicrystalline areas. A gradual increase in temperature leads to melting processes with different morphology in the bilayer profile. Far above the phase transition temperature the bilayer profile is still present. In the band-pass-filtered images (Fig. 2) no significant change in the width of the bilayer profile is visible.

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