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Plasmid DNA delivery using fluorescein-labeled arginine-rich peptides


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Title: Plasmid DNA delivery using fluorescein-labeled arginine-rich peptides
Authors: Oba, Makoto / Demizu, Yosuke / Yamashita, Hiroko / Kurihara, Masaaki / Tanaka, Masakazu
Issue Date: 1-Aug-2015
Publisher: Elsevier Limited
Citation: Bioorganic & Medicinal Chemistry, 23(15), pp.4911-4918; 2015
Abstract: Arginine (Arg)-rich peptides exhibit an effective cell-penetrating ability and deliver membrane-impermeable compounds into cells. In the present study, three types of Arg-rich peptides, R9 containing nine Arg residues, (RRG)3 containing six Arg and three glycine (Gly) residues, and (RRU)3 containing six Arg and three α-aminoisobutyric acid (Aib) residues, were evaluated for their plasmid DNA (pDNA) delivery and cell-penetrating abilities. The transfection efficiency of R9/pDNA complexes was much higher than those of (RRG)3 and (RRU)3/pDNA complexes, and was derived from the enhanced cellular uptake of R9/pDNA complexes. The replacement of three Arg residues with the neutral amino acid Gly and hydrophobic amino acid Aib drastically changed the cell-penetrating ability and physicochemical properties of peptide/pDNA complexes, resulting in markedly reduced transfection efficiency. A comparison of the R9 peptide administration forms between a peptide alone and peptide/pDNA complex revealed that the uptake of R9 peptides was more efficient for the complex than the peptide alone, but occurred through the same internalization mechanism. The results of the present study will contribute to the design of novel Arg-rich cell-penetrating peptides for pDNA delivery.
Keywords: Arginine / Cell-penetrating peptide / Drug delivery system / Gene transfer
URI: http://hdl.handle.net/10069/35783
ISSN: 09680896
DOI: 10.1016/j.bmc.2015.05.025
Rights: © 2015 Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/35783

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