Development of intracellular delivery method of proteins by hetero-dimerized leucine zippers

• Project/Area Number: 25410181
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Kinki University
• Principal Investigator: KITAMATSU Mizuki 近畿大学, 理工学部, 講師 (60379716)
• Co-Investigator(Kenkyū-buntansha): MICHIUE Hiroyuki 岡山大学, 大学院医歯薬学総合研究科, 助教 (20572499)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ペプチド / DDS / 細胞 / ロイシンジッパー / 細胞内運搬ペプチド / p53タンパク質 / Nanogタンパク質 / ペプチド核酸 / p53 / Nanog / Beclin-1

Outline of Final Research Achievements

For purpose of treatment of disease, we develop a method for delivering a functional proteins or functional peptides into cells. In this work, we synthesized an autophagy-inducing peptide (Beclin 1) modified with a hetero-dimerization leucine zipper peptide (LzK). We also synthesized a cell-penetrating peptide modified with a pair of LzK (LzE). When these peptides were mixed, Beclin 1 was successfully delivered into the cell, and the peptide induced autophagy.

Research Products

• [Journal Article] Novel leucine zipper motif-based hybrid peptide delivers functional peptide cargo inside cells. (2015)
  • Author(s): Hakata, Y., S. Tsuchiya, H. Michiue, T. Ohtsuki, H. Matsui, M. Miyazawa, and M. Kitamatsu
  • Journal Title: Chem. Comm. Volume: 51 Issue: 2 Pages: 413-416
  • DOI: 10.1039/c4cc07459a
  • Peer Reviewed / Open Access
• [Presentation] Peptide nucleic acid that conjugates with a cell-penetrating peptide via a disulfide bond for detecting a specific small RNA inside cells (2015)
  • Author(s): Mizuki Kitamatsu and Takashi Ohtsuki
  • Organizer: Pacifichem2015
  • Place of Presentation: Honolulu, Hawaii, USA
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] ペプチドハイブリッド法によるオートファジー誘導ペプチドの細胞内輸送 (2014)
  • Author(s): 鷺森直人、北松瑞生、博多義之、宮澤正顯
  • Organizer: 第29回関西地区ペプチドセミナー
  • Place of Presentation: 大阪府・吹田市・関西大学（千里山キャンパス）
  • Year and Date: 2014-11-29
• [Presentation] ペプチド‐ペプチド ハイブリッド法によるオートファジー誘導ペプチドの効果的輸送 (2014)
  • Author(s): 鷺森直人、博多義之、北松瑞生
  • Organizer: 第46回若手ペプチド夏の勉強会
  • Place of Presentation: 京都府・宮津市・京都府立青少年海洋センター
  • Year and Date: 2014-08-05
• [Presentation] Delivery of peptides into cells by peptide-peptide hybrid method (2014)
  • Author(s): M. Kitamatsu, T. Ohtsuki
  • Organizer: 15th Tetrahedron Symposium
  • Place of Presentation: London, UK
  • Year and Date: 2014-06-26