Chemical Biology in internalization of membrane-permeable peptides

• Project/Area Number: 19209004
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Kyoto University
• Principal Investigator: FUTAKI Shiroh Kyoto University, 化学研究所, 教授 (50199402)
• Co-Investigator(Kenkyū-buntansha): NAKASE Ikuhiko 京都大学, 化学研究所, 助教 (40432322)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥51,350,000 (Direct Cost: ¥39,500,000、Indirect Cost: ¥11,850,000); Fiscal Year 2009: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2008: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000); Fiscal Year 2007: ¥36,920,000 (Direct Cost: ¥28,400,000、Indirect Cost: ¥8,520,000)
• Keywords: アルギニンペプチド / 膜透過ペプチド / マクロピノサイトーシス / 受容体 / 細胞内移行 / 細胞膜 / 光反応性架橋団 / 薬物送達 / アルギニン / 細胞内情報伝達 / アクチン重合化

Research Abstract

Involvement of macropinocytosis to the internalization of arginine-rich membrane-permeable peptides has been suggested. In this study, using an R12 peptide bearing diazirine-based photo-reactive crosslinkers, a potential receptor to induce macropinocytosis by the interaction with R12 was identified. It was also elucidated that internalization efficiency of arginine-rich peptides are greatly affected by the peptide concentration, presence of serum, addition of hydrophobic segments and so on.

Research Products

• [Journal Article] Cell-surface accumulation of flock house virus-derived peptide leads to efficient internalization via macropinocytosis. (2009)
  • Author(s): Nakase I, Hirose H, Tanaka G, Tadokoro A, Kobayashi S, Takeuchi T, Futaki S.
  • Journal Title: Mol. Ther. 17 Pages: 1868-76
• [Journal Article] Enhanced intracellular delivery using arginine-rich peptides by the addition of penetration accelerating sequences (Pas). (2009)
  • Author(s): Takayama K, Nakase I, Michiue H, Takeuchi T, Tomizawa K, Matsui H, Futaki S.
  • Journal Title: J. Control. Release 138 Pages: 128-33
  • NAID: 120002723158
• [Journal Article] Cellular uptake, distribution and cytotoxicity of the hydrophobic cell penetrating peptide sequence PFVYLI linked to the proapoptotic domain peptide PAD. (2009)
  • Author(s): Watkins CL, Brennan P, Fegan C, Takayama K, Nakase I, Futaki S, Jones AT.
  • Journal Title: J. Control. Release 140 Pages: 237-44
• [Journal Article] Low concentration thresholds of plasma membranes for rapid energy-independent translocation of a cell-penetrating peptide. (2009)
  • Author(s): Watkins CL, Schmaljohann D, Futaki S, Jones AT.
  • Journal Title: Biochem. J. 420 Pages: 179-89
• [Journal Article] Novel system to achieve one-pot modification of cargo molecules with oligoarginine vectors for intracellular delivery. (2009)
  • Author(s): Takayama K, Tadokoro A, Pujals S, Nakase I, Giralt E, Futaki S.
  • Journal Title: Bioconjug. Chem. 20 Pages: 249-57
• [Journal Article] Cell-surface accumulation of flock house virus-derived peptide leads to efficient internalization via macropinocytosis (2009)
  • Author(s): Nakase I, Hirose H, Tanaka G, Tadokoro A, Kobayshi S, Takeuchi T, Futaki S.
  • Journal Title: Mol. Ther 17 Pages: 1868-1876
  • Peer Reviewed
• [Journal Article] Enhanced intracellular delivery using arginine-rich peptides by the addition of penetration accelerating sequences (Pas) (2009)
  • Author(s): Takayama K, Nakase I, Michiue H, Takeuchi T, Tomizawa K, Matsui H, Futaki S.
  • Journal Title: J. Control. Release 138 Pages: 128-133
  • NAID: 120002723158
  • Peer Reviewed
• [Journal Article] Cellular uptake, distribution and cytotoxicity of the hydrophobic cell penetrating peptide sequence PFVYLI linked to the proapoptotic domain peptide (2009)
  • Author(s): Watkins CL, Brennan P, Fegan C, Takayama K, Nakase I, Futaki S, Jones AT.
  • Journal Title: J. Control. Release 140 Pages: 237-244
  • Peer Reviewed
• [Journal Article] Low concentration thresholds of plasma membranes for rapid energy-independent translocation of a cel penetrating peptide (2009)
  • Author(s): Watkins CL, Schmaljohann D, Futaki S, Jones AT
  • Journal Title: Biochem J
  • Peer Reviewed
• [Journal Article] Novel system to achieve one-pot modification of cargo molecules with oligoarginine vectors for intracellular delivery (2009)
  • Author(s): Takayama K, Tadokoro A, Pujals S, Nakase I, Giralt E, Futaki S.
  • Journal Title: Bioconjug Chem 20 Pages: 249-257
  • Peer Reviewed
• [Journal Article] Low Concentration Thresholds of Plasma Membranes for Rapid Rnergy-Independent Translocation of a Cell Penetrating Peptide (2009)
  • Author(s): Watkins CL
  • Journal Title: Biochem. J. (印刷中)
  • Peer Reviewed
• [Journal Article] Cellular internalization and distribution of arginine-rich peptides as a function of extracellular peptide concentration, serum, and plasma membrane associated proteoglycans. (2008)
  • Author(s): Kosuge M, Takeuchi T, Nakase I, Jones AT, Futaki S.
  • Journal Title: Bioconjug. Chem. 19 Pages: 656-64
• [Journal Article] Cellular Internalization and Distribution of Arginine-Rich Peptides as a Function of Extracellular Peptide Concentration, Serum, and Plasma Membrane Associated Proteoglycans (2008)
  • Author(s): Kosuge M
  • Journal Title: Bioconjug. Chem. 19 Pages: 656-664
  • Peer Reviewed
• [Presentation] Cellular dynamics involved in the internalization of arginine-rich cell penetrating peptides (2009)
  • Author(s): Futaki S.
  • Organizer: 3rd Asia-Pacific International Peptide Symposium
  • Place of Presentation: Jeju, Korea
  • Year and Date: 2009-11-10
• [Presentation] Chemical and Biological Factors that Affect the Internalization of Arginine-Rich Cell-Penetrating Peptides (2009)
  • Author(s): Futaki S.
  • Organizer: Fifth Peptide Engineering Meeting (PEM5)
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2009-10-27
• [Presentation] Chemical and Biological Factors that Affect the Internalization of Arginine-Rich Cell-Penetrating Peptides (2009)
  • Author(s): Shiroh Futaki
  • Organizer: Fifth Peptide Engineering Meeting (PEM5)
  • Place of Presentation: Barchlona, Spain
  • Year and Date: 2009-10-27
• [Presentation] アルギニンペプチドと細胞膜との相互作用 (2009)
  • Author(s): 二木史朗
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-22
• [Presentation] Chemical and Biological Factors that Affect the Internalization of Arginine-Rich Cell-Penetrating Peptides (2009)
  • Author(s): Futaki S.
  • Organizer: PepVec2009 Meeting on "Intracellular Delivery of Therapeutic Molecules: From Bench to Bedside"
  • Place of Presentation: Montpellier, France
  • Year and Date: 2009-09-01
• [Presentation] Chemical and Biological Factors that Affect the Internalization of Arginine-Rich Cell-Penetrating Peptides (2009)
  • Author(s): Shiroh Futaki
  • Organizer: PepVec2009 Meeting on "Intracellular Delivery of Therapeutic Molecules : From Bench to Bedside"
  • Place of Presentation: Montpellier, France
  • Year and Date: 2009-09-01
• [Presentation] アルギニンペプチドを用いた蛋白質の細胞内導入 (2009)
  • Author(s): 二木史朗
  • Organizer: 第15回日本遺伝子治療学会
  • Place of Presentation: 大阪大学
  • Year and Date: 2009-07-09
• [Presentation] Arginine-rich peptides as a vector of intracellular delivery (2008)
  • Author(s): Futaki S.
  • Organizer: 3rd International Workshop on Approaches to Single-Cell Analysis
  • Place of Presentation: Zurich, Switzerland
  • Year and Date: 2008-09-12
• [Presentation] Cellular dynamics of cell penetrating peptides (2008)
  • Author(s): Futaki S.
  • Organizer: 2nd International Symposium "Cellular Delivery of Therapeutic Macromolecules 2008"
  • Place of Presentation: Cardiff, UK
  • Year and Date: 2008-06-24
• [Presentation] アルギニンペプチドの細胞内移行のダイナミクス (2008)
  • Author(s): 二木史朗
  • Organizer: 第14回日本遺伝子治療学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2008-06-14
• [Presentation] Arginine-rich peptides and their internalization mechanisms (2007)
  • Author(s): Futaki S.
  • Organizer: Biochemical Society Focused Meeting
  • Place of Presentation: Telford, UK
  • Year and Date: 2007-05-10
• [Remarks] 新聞掲載知の最前線13・京大附置研究所センターの人々(読売新聞平成20年2月29日)
  • URL: http://www.scl.kyoto-u.ac.jp/~bfdc/index.html
• [Remarks]
  • URL: http://www.scl.kyoto-u.ac.jp/~bfdc/index.html
• [Remarks]
  • URL: http://www.scl.kyoto-u.ac.jp/~bfdc/index.html
• [Remarks]
  • URL: http://www.kuicr.kyoto-u.ac.jp/icr-bin/KUICR_info.pl?user=futaki+shiroh