Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors

PLoS One. 2015 Jun 25;10(6):e0130417. doi: 10.1371/journal.pone.0130417. eCollection 2015.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antimicrobial Cationic Peptides / administration & dosage
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell-Penetrating Peptides / administration & dosage*
  • Cysteamine / administration & dosage
  • Cysteamine / analogs & derivatives*
  • Furin / antagonists & inhibitors*
  • Furin / metabolism*
  • HIV-1 / chemistry
  • Humans
  • Peptide Fragments / administration & dosage*
  • Peptides / administration & dosage*
  • tat Gene Products, Human Immunodeficiency Virus / administration & dosage*


  • Antimicrobial Cationic Peptides
  • Cell-Penetrating Peptides
  • Pep-1 peptide
  • Peptide Fragments
  • Peptides
  • tat Gene Products, Human Immunodeficiency Virus
  • tat peptide (47-57), Human immunodeficiency virus 1
  • Cysteamine
  • Furin