title: X-pep, a novel cell-penetrating peptide motif derived from the hepatitis B virus.
abstract: Cell-penetrating peptides (CPPs) are able to penetrate the plasma membrane and gain access to the interior of any replicating or non-replicating cell, and are being considered as drug delivery agents. Here we describe the serendipitous discovery of a novel CPP motif (MAARLCCQ), designated X-pep, located at the extreme N-terminus of the X-protein of the hepatitis B virus. X-pep, and a C-terminally truncated form of the peptide (MAARL), readily penetrated HepG2 cells. Further truncation by removal of the terminal leucine residue impaired the cell-penetrating activity of peptide, indicating that MAARL is the active core of the peptide. X-pep is located adjacent to another CPP, namely Xentry, and like Xentry is unable to penetrate unactivated resting lymphocytes suggesting selective cell uptake. A D-isomeric form of the MAARL peptide was not cell-permeable, indicating that the cell-penetrating function of the peptide involves stereoselective interaction with a chiral receptor. The discovery of X-pep, which bears no resemblance to known CPPs, allows studies to be undertaken to determine additional characteristics of this novel CPP.
authors.affiliation: Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Kristopher
authors.initials: K
authors.lastname: Montrose
authors.affiliation: Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. Electronic address: gw.krissansen@auckland.ac.nz.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Krissansen
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active; D002460:Cell Line; D002463:Cell Membrane Permeability; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D016503:Drug Delivery Systems; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D013237:Stereoisomerism; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D057846:Cell-Penetrating Peptides; D015534:Trans-Activators; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: Cell-penetrating peptide; Cell-permeability; Hepatitis B virus; Stereoisomer; X-protein