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Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors.

Ramos-Molina B, Lick AN, Nasrolahi Shirazi A, Oh D, Tiwari R, El-Sayed NS, Parang K, Lindberg I - PLoS ONE (2015)

Bottom Line: These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors.In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%.In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro and also inhibited intracellular convertases.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, School of Medicine, University of Maryland-Baltimore, Baltimore, Maryland, United States of America.

ABSTRACT
Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro and also inhibited intracellular convertases. Our finding that cationic cell-penetrating peptides exert potent effects on cellular convertase activity should be taken into account when biological effects are assessed.

No MeSH data available.


Related in: MedlinePlus

Effect of HIV-1 TAT47-57 peptide on cell migration of fibrosarcoma HT1080 cells.Cells were incubated with either 10 μM of peptide or vehicle (water) for 24 h at 37°C and cell migration was measured as described in “Materials and Methods”. Results represent the mean ± S.D., N = 3. **P<0.05.
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pone.0130417.g002: Effect of HIV-1 TAT47-57 peptide on cell migration of fibrosarcoma HT1080 cells.Cells were incubated with either 10 μM of peptide or vehicle (water) for 24 h at 37°C and cell migration was measured as described in “Materials and Methods”. Results represent the mean ± S.D., N = 3. **P<0.05.

Mentions: Because of its inhibitory potency in vitro against furin, as well as its known cell permeability, we then analyzed the inhibitory capacity of the HIV-1 TAT47-57 peptide against cancer cell migration, a process dependent on the activity of cellular convertases. We incubated HT1080 fibrosarcoma cells together with a non-toxic quantity of the HIV-1 TAT47-57 peptide (10 μM). Fig 2 shows that incubation of cells with HIV-1 TAT47-57 resulted in significant inhibition of cell migration, similar to that obtained with the multi-Leu convertase inhibitor peptide [26,27].


Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors.

Ramos-Molina B, Lick AN, Nasrolahi Shirazi A, Oh D, Tiwari R, El-Sayed NS, Parang K, Lindberg I - PLoS ONE (2015)

Effect of HIV-1 TAT47-57 peptide on cell migration of fibrosarcoma HT1080 cells.Cells were incubated with either 10 μM of peptide or vehicle (water) for 24 h at 37°C and cell migration was measured as described in “Materials and Methods”. Results represent the mean ± S.D., N = 3. **P<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482483&req=5

pone.0130417.g002: Effect of HIV-1 TAT47-57 peptide on cell migration of fibrosarcoma HT1080 cells.Cells were incubated with either 10 μM of peptide or vehicle (water) for 24 h at 37°C and cell migration was measured as described in “Materials and Methods”. Results represent the mean ± S.D., N = 3. **P<0.05.
Mentions: Because of its inhibitory potency in vitro against furin, as well as its known cell permeability, we then analyzed the inhibitory capacity of the HIV-1 TAT47-57 peptide against cancer cell migration, a process dependent on the activity of cellular convertases. We incubated HT1080 fibrosarcoma cells together with a non-toxic quantity of the HIV-1 TAT47-57 peptide (10 μM). Fig 2 shows that incubation of cells with HIV-1 TAT47-57 resulted in significant inhibition of cell migration, similar to that obtained with the multi-Leu convertase inhibitor peptide [26,27].

Bottom Line: These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors.In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%.In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro and also inhibited intracellular convertases.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, School of Medicine, University of Maryland-Baltimore, Baltimore, Maryland, United States of America.

ABSTRACT
Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro and also inhibited intracellular convertases. Our finding that cationic cell-penetrating peptides exert potent effects on cellular convertase activity should be taken into account when biological effects are assessed.

No MeSH data available.


Related in: MedlinePlus