title: Xentry, a new class of cell-penetrating peptide uniquely equipped for delivery of drugs.
abstract: Here we describe an entirely new class of cell-penetrating peptide (CPP) represented by the short peptide Xentry (LCLRPVG) derived from an N-terminal region of the X-protein of the hepatitis B virus. Xentry permeates adherent cells using syndecan-4 as a portal for entry, and is uniquely restricted from entering syndecan-deficient, non-adherent cells, such as resting blood cells. Intravenous injection of Xentry alone or conjugated to β-galactosidase led to its delivery to most tissues in mice, except circulating blood cells. There was a predilection for uptake by epithelia. Anti-B-raf antibodies and siRNAs linked to Xentry were capable of killing B-raf-dependent melanoma cells. Xentry represents a new class of CPP with properties that are potentially advantageous for life science and therapeutic applications.
authors.affiliation: Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1005, New Zealand.
authors.forename: Kristopher
authors.initials: K
authors.lastname: Montrose
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Xueying
authors.initials: X
authors.lastname: Sun
authors.forename: Siouxsie
authors.initials: S
authors.lastname: Wiles
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Krissansen
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D008657:Metabolic Clearance Rate; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000378:metabolism*
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers