title: Identification and characterization of a novel cell-penetrating peptide.
abstract: Cell-penetrating peptides (CPPs) are short amino acid sequences that promote their own translocation across cell plasma membrane. When linked with cargo such as polypeptides, nucleic acid, or liposomes, CPPs can facilitate the transport of these entities across the cell membrane. Therefore, CPPs are receiving increased interest in drug delivery and gene therapy. The majority of CPPs identified so far are polycationic peptides which interact with heparin sulfate chains of plasma membrane for internalization. Here, we report the identification and characterization of a conformationally constrained 13 amino acid peptide (CVQWSLLRGYQPC, designated as S41) which is clearly distinct from classical polycationic peptides. Immunofluorescence assay was employed to test the cellular uptake of S41 in mouse neuroblastoma cell line Neuro2A (N2A) and rat cerebellar granule neurons (CGNs). Internalization of S41 was further examined in N2A cells by means of mutational analysis, flow cytometry and confocal microscopy. Our results demonstrate that S41 can enter cells through lipid rafts dependent endocytosis.
authors.affiliation: Department of Biomedical Sciences, Division of Infectious Disease, Tufts Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Sheng
authors.forename: George
authors.initials: G
authors.lastname: Oyler
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Kim
authors.initials: K
authors.lastname: Janda
authors.forename: Charles B
authors.initials: CB
authors.lastname: Shoemaker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004705:Endocytosis; D005434:Flow Cytometry; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D051381:Rats
chemical_list: D019151:Peptide Library; D010455:Peptides