A protein transduction method using oligo-arginine (3R) for the delivery of transcription factors into cell nuclei

Takashi Hitsuda, Hiroyuki Michiue, Mizuki Kitamatsu, Atsushi Fujimura, Feifei Wang, Takahiro Yamamoto, Xiao Jian Han, Hiroshi Tazawa, Atsuhito Uneda, Iori Ohmori, Tei ichi Nishiki, Kazuhito Tomizawa, Hideki Matsui

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Protein transduction with cell-penetrating peptides such as poly-arginine and HIV TAT peptides is widely used to deliver proteins, peptides, siRNA and biologically active compounds It has been thought that poly-arginine peptides transduce proteins in a manner dependent on the number of arginine residues and oligo-peptides such as three arginines (3R) are ineffective Here we showed that 3R-fused proteins were effectively delivered and functioned in cells co-treated with pyrenebutyrate, a counteranion bearing an aromatic hydrophobic moiety Little 3R was transduced in glioma cells without pyrenebutyrate whereas the oligo-arginine was effectively delivered with pyrenebutyrate Enhanced green fluorescence protein (eGFP) fused with 3R was effectively delivered into various kinds of cells including primary cultured cells and suspended cells in the presence of pyrenebutyrate p53 fused with 3R (3R-p53) was delivered into glioma cells without pyrenebutyrate but could not be translocated into the nucleus In contrast, 3R-p53 was observed in nuclei of glioma cells when co-applied with pyrenebutyrate Although 3R-p53 was delivered less effectively than 11R-p53 with pyrenebutyrate, its transcriptional activity was higher than that of 11R-p53 Moreover, a single administration of 3R-p53 with pyrenebutyrate significantly inhibited the growth of cancer cells These results suggest protein transduction using an oligo-arginine (3R) with pyrenebutyrate to be a good tool for the delivery of functional transcription factors and a promising method of treating cancer.

Original languageEnglish
Pages (from-to)4665-4672
Number of pages8
JournalBiomaterials
Volume33
Issue number18
DOIs
Publication statusPublished - Jun 1 2012

Keywords

  • Arginine
  • Drug delivery
  • EGFP
  • P53
  • Protein transduction
  • TAT

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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