Development of new BACE1 inhibitors : an approach for downsizing molecules

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790119
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Drug development chemistry
• Research Institution: Kogakuin University (2011); Kyoto Prefectural University of Medicine (2010)
• Principal Investigator: KAKIZAWA Taeko 工学院大学, 工学部, 講師 (60445963)
• Project Period (FY): 2010 – 2011
• Keywords: アルツハイマー病

Research Abstract

The enzyme BACE1 is a major target for developing drugs for the treatment of Alzheimer's disease, because it catalyzes the production of amyloid β peptide. We designed and synthesized several low-molecular-weight tetrapeptidic BACE1 inhibitors with high potency from KMI-927.

Research Products

• [Journal Article] Development of [Ile^<40>] HTLV-I protease inhibition assay using novel fluorogenic and chromogenic substrate (2011)
  • Author(s): H-O. Kumada, J-T. Nguyen, K. T. Kakizawa, K. Hidaka, T. Kimura, Y. Hayashi, and Y. Kiso
  • Journal Title: Journal of Peptide Science Volume: 17 Pages: 569-575
  • DOI: DOI:10.1002/psc.1375
  • Peer Reviewed
• [Journal Article] Self-assembly pathways of E22D-type amyloid β peptide mutants generated from non-aggregative O-acyl isopeptide precursors (2011)
  • Author(s): Y. Sohma, H. Wang, A. Taniguchi, Y. Hirayama, T. Kakizawa, M. Yamasaki, H. Mukai, and Y. Kiso
  • Journal Title: Bioorganic and Medicinal Chemistry Volume: 19 Pages: 3787-3792
  • DOI: doi:10.1016/j.bmc.2011.04.056
  • Peer Reviewed
• [Journal Article] Evaluation of superior BACE1 cleavage sequences containing unnatural amino acids (2011)
  • Author(s): T. Kakizawa, A. Sanjoh, A. Kobayashi, Y. Hattori, K. Teruya, and K. Akaji
  • Journal Title: Bioorganic and Medicinal Chemistry Volume: 19 Pages: 2785-2789
  • DOI: doi:10.1016/j.bmc.2011.03.056
  • Peer Reviewed
• [Journal Article] Dehydrocoupling reactions of secondary and primary amine-borane adducts catalyzed by half-sandwich carbonyl complexes, [CpMn(CO)_3], [(η^6-C_6H_6) Cr(CO)_3], and [CpV(CO)_4] (2011)
  • Author(s): T. Kakizawa, Y. Kawano, K. Naganeyama, and M. Shimoi
  • Journal Title: Chemistry Letters Volume: 40 Pages: 171-173
  • DOI: doi:10.1246/cl.2011.171
  • Peer Reviewed
• [Journal Article] Tetrapeptides, as small-sized peptidic inhibitors ; synthesis and their inhibitory activity against BACE1 (2010)
  • Author(s): T. Kakizawa, K. Hidaka, D. Hamada, R. Yamaguchi, T. Uemura, H. Kitamura, H. D. Tagad, T. Hamada, Z. Ziora, Y. Hamada, T. Kimura, and Y. Kiso
  • Journal Title: Journal of Peptide Science Volume: 16 Pages: 257-262
  • DOI: DOI:10.1002/psc.1238
  • Peer Reviewed
• [Presentation] Design and Preparation of the Tetrapeptides as Low Molecular Sized BACE1 Inhibitors (2010)
  • Author(s): Taeko Kakizawa・Koushi Hidaka・Daisuke Hamada・Ryoji Yamaguchi・Tsuyoshi Uemura・Hitomi Kitamura・Harichandra D. Tagad・Takeshi Hamada・Zyta Ziora・Yoshio Hamada・Tooru Kimura・Yoshiaki Kiso
  • Organizer: 5th International Peptide Symposium
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20101204-09
• [Presentation] Click Peptide : Application to E22Δ-type Mutant of Amyloid β Peptide (2010)
  • Author(s): Hui Wang・Youhei Sohma・Atsuhiko Taniguchi・Yuta Hirayama・Taeko Kakizawa・Hidehito Mukai・Yoshiaki Kiso
  • Organizer: 5th International Peptide Symposium
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20101204-09
• [Presentation] Evaluation of substrate specificities for BACE1 using synthetic peptide libraries (2010)
  • Author(s): Taeko Kakizawa・Yasunao Hattori・Kenta Teruya・Akira Sanjoh・Kenichi Akaji
  • Organizer: 5th International Peptide Symposium
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20101204-09
• [Presentation] ペプチドライブラリーを用いたBACE 1基質特異性の検討 (2010)
  • Author(s): 柿澤多惠子・服部恭尚・照屋健太・三城明・赤路健一
  • Organizer: 第29回メディシナルケミストリーシンポジウム
  • Place of Presentation: 京都テルサ
  • Year and Date: 20101117-19
• [Presentation] LC-MSを用いたペプチドライブラリーからのBACE 1基質特異性のスクリーニング (2010)
  • Author(s): 柿澤多惠子・服部恭尚・照屋健太・三城明・赤路健一
  • Organizer: 第6回3大学連携研究フォーラム
  • Place of Presentation: 京都府立大学
  • Year and Date: 2010-12-07
• [Remarks] 国際会議のプロシーディング等(1) T. Kakizawa, K. Hidaka, D. Hamada, R. Yamaguchi, T. Uemura, H. Kitamura, H. D. Tagad, T. Hamada, Z. Ziora, Y. Hamada, T. Kimura, and Y. Kiso, Japanese Peptide Society,「Design and Preparation of the Tetrapeptides as Low Molecular Sized BACE1 Inhibitors」Peptide Science 2010, ed. N. Fujii and Y. Kiso, p.252(2011).
• [Remarks] (2) H. Wang, Y. Sohma, A. Taniguchi, Y. Hirayama, T. Kakizawa, H. Mukai, and Y. Kiso, Japanese Peptide Society,「Click Peptide : Application to E22Δ-type Mutant of Amyloid β Peptide」Peptide Science 2010, ed. N. Fujii and Y. Kiso, p.221(2011).
• [Remarks] (3) T. Kakizawa, Y. Hattori, K. Teruya, A. Sanjoh, and K. Akaji, Japanese Peptide Society,「Evaluation of substrate specificities for BACE1 using synthetic peptide libraries」Peptide Science 2010, ed. N. Fijii and Y. Kiso, p.121(2011).
• [Remarks] (4) H. Wang, T. Kakizawa, A. Taniguchi, T. Mizuguchi, Y. Sohma, H. Mukai, T. Kimura, and Y. Kiso, Japanese Peptide Society,「Investigation of Aβ1.42 Mutants Based on O-Acyl Isopeptide Method ; Synthesis of O-Acyl Isopeptides and in Situ Production of their