title: Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors.
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.
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, University of Maryland-Baltimore, Baltimore, Maryland, United States of America.
authors.forename: Bruno
authors.initials: B
authors.lastname: Ramos-Molina
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, University of Maryland-Baltimore, Baltimore, Maryland, United States of America.
authors.forename: Adam N
authors.initials: AN
authors.lastname: Lick
authors.affiliation: Chapman University, School of Pharmacy, Irvine, California, United States of America.
authors.forename: Amir
authors.initials: A
authors.lastname: Nasrolahi Shirazi
authors.affiliation: Chapman University, School of Pharmacy, Irvine, California, United States of America.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Oh
authors.affiliation: Chapman University, School of Pharmacy, Irvine, California, United States of America.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Tiwari
authors.affiliation: Chapman University, School of Pharmacy, Irvine, California, United States of America.
authors.forename: Naglaa Salem
authors.initials: NS
authors.lastname: El-Sayed
authors.affiliation: Chapman University, School of Pharmacy, Irvine, California, United States of America.
authors.forename: Keykavous
authors.initials: K
authors.lastname: Parang
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, University of Maryland-Baltimore, Baltimore, Maryland, United States of America.
authors.forename: Iris
authors.initials: I
authors.lastname: Lindberg
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage*; D003543:Cysteamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045683:Furin / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry; D006801:Humans; D010446:Peptide Fragments / Q000008:administration & dosage*; D010455:Peptides / Q000008:administration & dosage*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage*
chemical_list: D023181:Antimicrobial Cationic Peptides; D057846:Cell-Penetrating Peptides; C503924:Pep-1 peptide; D010446:Peptide Fragments; D010455:Peptides; D054322:tat Gene Products, Human Immunodeficiency Virus; C497137:tat peptide (47-57), Human immunodeficiency virus 1; D003543:Cysteamine; D045683:Furin