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.
Highlights
Cationic peptides present within envelope proteins are used by many viruses to gain entry into host cells
In order to assess the possibility that cell-penetrating peptides (CPPs) used for the intracellular delivery of proteins and drugs might exert side effects on cellular proprotein convertases, in the study reported below we have investigated their inhibitory effects on convertase activity, both in vitro and within cells
The Chariot reagent inhibited furin at micromolar concentrations (~20% at 10 μM; ~60% at 100 μM), much less potently than the human immunodeficiency virus type 1 (HIV-1) TAT47-57 peptide (Fig 1B). This difference may be attributable to the greater number of arginine residues present in the HIV-1 TAT47-57 peptide sequence (Table 1)
Summary
Cationic peptides present within envelope proteins are used by many viruses to gain entry into host cells. In addition to the TAT peptide, numerous natural and synthetic CPPs have been described in the literature (i.e. penetratrin [7], Pep-1/Chariot [8], and polyarginine-containing peptides [9,10,11]) and are commercially available. Variants on this theme include certain cyclic polyarginine peptides with high cell permeability and stability which have been recently used for the delivery of a PLOS ONE | DOI:10.1371/journal.pone.0130417. Variants on this theme include certain cyclic polyarginine peptides with high cell permeability and stability which have been recently used for the delivery of a PLOS ONE | DOI:10.1371/journal.pone.0130417 June 25, 2015
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
