Medicinal application of intrinsically disordered proteins of unknown function

• Project/Area Number: 26650048
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biophysics
• Research Institution: Nagoya University
• Principal Investigator: HIROAKI Hidekazu 名古屋大学, 創薬科学研究科, 教授 (10336589)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 凍結保護 / バイオ医薬品添加剤 / コールドチェイン / 分子盾効果 / 天然変性タンパク質 / 医薬品添加剤 / 国内優先権による出願 / 国際特許出願 / バイオ医薬品安定化剤 / 凍結保護剤 / 再生・細胞医療 / 原著論文発表 / 医療応用 / 国内優先権に基づく出願

Outline of Final Research Achievements

Intrinsically disordered proteins (IDPs), polypeptides that lack a stable compact structure, are known to exert the two major molecular functions, “fly-casting mechanism” and “coupled folding and binding”. Plant stress-responsible protein dehydrins and silkworm sericins are the examples of IDPs. These exert cryoprotective activity against enzymes and cultivated cells, respectively. If IDP’s molecular functions are originated from their physical properties, similar functions may also exist in human-genome derived IDPs.
Based on the concept, we started to screen several human IDPs using cryoprotective activity against the model enzyme lactose dehydrogenase as an index. Finally, we succeeded in finding a 20 aa IDP peptide that showed cryoprotective activity against NHDF cell.

Research Products

• [Journal Article] Nuclear magnetic resonance evidence for the dimer formation of beta amyloid peptide 1-42 in 1,1,1,3,3,3-hexafluoro-2-propanol. (2016)
  • Author(s): Yoshiki Shigemitsu, Naoko Iwaya, Natsuko Goda, Mizuki Matsuzaki, Takeshi Tenno, Akihiro Narita, Minako Hoshi, Hidekazu Hiroaki
  • Journal Title: Analytical Biochemistry Volume: 498 Pages: 59-67
  • DOI: 10.1016/j.ab.2015.12.021
  • Peer Reviewed
• [Journal Article] A Method for Systematic Assessment of Intrinsically Disordered Protein Regions by NMR (2015)
  • Author(s): Goda, N., Shimizu, K., Kuwahara, Y., Tenno, T., Noguchi,T., Ikegami, T., Ota, M., and Hiroaki, H
  • Journal Title: Intternational Journal of Molecular Sciences Volume: 16 Issue: 7 Pages: 15743-15760
  • DOI: 10.3390/ijms160715743
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An optimized Npro-based method for the expression and purification of intrinsically disordered proteins for an NMR study. (2015)
  • Author(s): Goda, N., Matsuo, N., Tenno, T., Ishino, S., Ishino, Y., Fukuchi, S., Ota, M., and Hiroaki, H
  • Journal Title: Intrinsically Disordere Proteins Volume: 3 Issue: 1 Pages: 1-6
  • DOI: 10.1080/21690707.2015.1011004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 用語解説：天然変性タンパク質 (2015)
  • Author(s): 廣明秀一
  • Journal Title: 日本再生医療学会雑誌-再生医療 Volume: 13 Pages: 52-53
• [Journal Article] 用語解説：天然変性タンパク質 (2015)
  • Author(s): 廣明秀一
  • Journal Title: 日本再生入用学会雑誌-再生医療 Volume: 13
• [Journal Article] Multiple Interactions of the Intrinsically Disordered Region between the N-terminal Helicase and C-terminal Nuclease Domains (2014)
  • Author(s): S. Ishino, T. Yamagami, M. Kitamura, N. Kodera, T. Mori, S. Sugiyama, T. Ando, N. Goda, T. Tenno, H. Hiroaki, and Y. Ishino
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 31 Pages: 21627-21639
  • DOI: 10.1074/jbc.m114.554998
  • Peer Reviewed
• [Presentation] HFIP中におけるβアミロイド(1-42)ペプチドの二量体形成 (2016)
  • Author(s): 重光佳基、岩谷奈央子、天野剛志、合田名都子、松崎瑞季、成田哲博、星美奈子、廣明秀一
  • Organizer: 201５年度生物物物理学会中部地区講演会
  • Place of Presentation: 愛知県岡崎市
  • Year and Date: 2016-02-29
• [Presentation] 化学シフト温度依存性に着目した天然変性タンパク質領域の同定法 (2016)
  • Author(s): 岡崎寛貴、松尾直紀、天野剛志、廣明秀一
  • Organizer: 201５年度生物物物理学会中部地区講演会
  • Place of Presentation: 愛知県岡崎市
  • Year and Date: 2016-02-29
• [Presentation] 医療応用を志向したタンパク質・細胞の凍結保護剤 (2016)
  • Author(s): 廣明秀一
  • Organizer: 第２回メディカルメッセ（中部地区 医療・バイオ系シーズ発表会）
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2016-02-03
• [Presentation] "Use of principal component analysis of 1H-15N NMR spectra of amyloid- (1–42) peptide for characterization of fibril formation inhibitors. " (2015)
  • Author(s): H. Hiroaki*, N. Iwaya, M. Matsuzaki, Y. Shigemitsu, N. Goda, Y. Abe, M. Hoshi, A. Narita
  • Organizer: PACIFICHEM 2015
  • Place of Presentation: Honolulu, Hawaii, USA
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Cryoprotective Activity in Human Genome-derived Intrinsically Disordered Proteins and Their Pharmaceutical Applications (2015)
  • Author(s): H. Hiroaki*
  • Organizer: 2015 The 5th NU-TECH ROUND TABLE
  • Place of Presentation: Raleigh, NC, USA
  • Year and Date: 2015-11-04
  • Int'l Joint Research / Invited
• [Presentation] ヒトゲノム配列に含まれる天然変性タンパク質の医療応用 (2015)
  • Author(s): 松尾直紀、合田名都子、清水佳奈、福地佐斗志、太田元規、廣明秀一
  • Organizer: 第135回日本薬学会年会
  • Place of Presentation: 神戸学院大学（神戸市）
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 天然変性タンパク質に見出されたタンパク質に対する凍結保護活性の研究 (2015)
  • Author(s): 松尾直紀、合田名都子、清水佳奈、福地佐斗志、太田元規、廣明秀一
  • Organizer: 2014年度⽣物物物理学会中部⽀部講演会
  • Place of Presentation: 岡崎カンファレンスホール（岡崎市）
  • Year and Date: 2015-03-10
• [Presentation] 医療応用を志向したタンパク質の凍結・凍結乾燥保護剤 (2014)
  • Author(s): 廣明秀一
  • Organizer: 新技術説明会-中部地区医療・バイオ系シーズ発表会2014
  • Place of Presentation: ウィンクあいち（名古屋市）
  • Year and Date: 2014-12-10
• [Presentation] 天然変性タンパク質がもつ凍結保護作用の発見 (2014)
  • Author(s): 松尾直紀、合田名都子、清水佳奈、福地佐斗志、太田元規、廣明秀一
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 天然変性タンパク質に広く認められた凍結保護作用の評価 (2014)
  • Author(s): 松尾直紀、合田名都子、清水佳奈、福地佐斗志、太田元規、廣明秀一
  • Organizer: 第14回日本蛋白質科学会年会
  • Place of Presentation: ワークピア横浜（横浜市）
  • Year and Date: 2014-06-25 – 2014-06-27
• [Book] Special Periodical Reports; Nuclear Magnetic Resonance Volume 45 (2016)
  • Author(s): Hiroaki, H
  • Total Pages: 22
  • Publisher: Royal Society of Chemistry
• [Remarks] 天然変性タンパク質のNMR解析と医療応用
  • URL: http://presat-vector.org/hiroaki-lab/?p=116
• [Remarks] 【特許出願情報】「タンパク質凍結保護剤」に関する特許出願
  • URL: http://presat-vector.org/hiroaki-lab/?p=1048
• [Remarks] 新規のバイオ医薬品の保存用安定化剤
  • URL: http://www.engg.nagoya-u.ac.jp/techno/techno2015/booth/no23.php
• [Patent(Industrial Property Rights)] タンパク質凍結保存用保護剤 (2015)
  • Inventor(s): 廣明秀一 天野名都子 松尾直紀 太田元規 福地佐斗志 岩村佳奈
  • Industrial Property Rights Holder: 国立大学法人名古屋大学他
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-01-06
  • Overseas