Design and medicinal chemistry research on drugs for difficult diseases based on molecular recognition of proteases

• Project/Area Number: 18209005
• 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 Pharmaceutical University
• Principal Investigator: KISO Yoshiaki Kyoto Pharmaceutical University, 薬学部, 教授 (40089107)
• Co-Investigator(Kenkyū-buntansha): KIMURA Tooru 京都薬科大学, 薬学部, 准教授 (70204980)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥35,620,000 (Direct Cost: ¥27,400,000、Indirect Cost: ¥8,220,000); Fiscal Year 2008: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000); Fiscal Year 2007: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000); Fiscal Year 2006: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
• Keywords: プロテアーゼ / 分子認識 / プロテアーゼ阻害剤 / ドラッグデザイン / 基質遷移状態 / β-セクレターゼ / プラスメプシン / HIVプロテアーゼ

Research Abstract

我々は基質遷移状態概念に基づいて、アスパラギン酸プロテアーゼに属するHIVプロテアーゼ阻害剤のデザインと合成を行い、ヒドロキシメチルカルボニルイソステアが、理想的な遷移状態ミミックであることを見いだし、低分子化にも成功し、耐性と副作用の問題点克服の可能性も示した。このような有用な阻害剤設計の方法論を応用し、様々な難病克服を目指した分子認識に基づく治療薬のデザイン・合成と構造最適化・プロドラッグ等の医薬化学研究を行いその開発への指針を示した。

Research Products

• [Journal Article] New developments for the design, synthesis and biological evaluation of potent SARS-CoV 3Cl^<pro> inhibitors (2009)
  • Author(s): T. Regnier, D. Sarma, K. Hidaka, U. Bacha, E. Freire, Y. Hayashi, Y. Kiso
  • Journal Title: Bioorg. Med. Chem. Lett 19(10) Pages: 2722-2727
  • Peer Reviewed
• [Journal Article] Significance of interactions of BACE1-Arg235 with its ligands and design of BACE1 inhibitors with P2 pyridine scaffold (2009)
  • Author(s): Y. Hamada, H. Ohta, N. Miyamoto, D. Sarma, T. Hamada, T. Nakanishi, M. Yamasaki, A. Yamani, S. Ishiura, Y. Kiso
  • Journal Title: Bioorg. Med. Chem. Lett 19(9) Pages: 2435-2439
  • Peer Reviewed
• [Journal Article] Crystal structure of the histo-aspartic protease (HAP) from Plasmodium falciparum (2009)
  • Author(s): P. Bhaumik, H. Xiao, C. L. Parr, Y. Kiso, A. Gustchina, R. Y. Yada, A. Wlodawer
  • Journal Title: J. Mol. Biol 388(3) Pages: 520-540
  • Peer Reviewed
• [Journal Article] Recent progress in the drug discovery of non-peptidic BACE1 inhibitors (2009)
  • Author(s): Y. Hamada, Y. Kiso
  • Journal Title: Expert Opinion on Drug Discovery 4(4) Pages: 391-416
  • Peer Reviewed
• [Journal Article] Structure of HIV-1 protease in complex with potent inhibitor KNI-272 determined by high resolution X-ray and neutron crystallography, Proc (2009)
  • Author(s): M. Adachi, T. Ohhara, K. Kurihara, T. Tamada, E. Honjo, N. Okazaki, S. Arai, Y. Shoyama, K. Kimura, H. Matsumura, S. Sugiyama, H. Adachi, K. Takano, Y. Mori, K. Hidaka, T. Kimura, Y. Hayashi, Y. Kiso, R. Kuroki
  • Journal Title: Natl. Acad. Sci. USA 106(12) Pages: 4641-4646
  • Peer Reviewed
• [Journal Article] "Click peptide" : pH-triggered in situ production and aggregation of monomer As1-42 (2009)
  • Author(s): A. Taniguchi, Y. Sohma, Y. Hirayama, H. Mukai, T. Kimura, Y. Hayashi, K. Matsuzaki, Y. Kiso
  • Journal Title: Chem Bio Chem 10(4) Pages: 710-715
  • Peer Reviewed
• [Journal Article] Inhibition by KMI-574 leads to dislocalization of BACE1 from lipid rafts (2009)
  • Author(s): M. Ebina, E. Futai, C. Tanabe, N. Sasagawa, Y. Kiso, S. Ishiura
  • Journal Title: J. Neurosci. Res 87(2) Pages: 360-360
  • Peer Reviewed
• [Journal Article] Structure of HIV-1 protease incomplex with potent inhibitor KNI-272 determinedby high-resolution X-ray and neutron crystallography (2009)
  • Author(s): M. Adachi, T. Kimura, Y. Kiso, 他16名
  • Journal Title: Proc.Natl.Acad.Sci.USA 106 Pages: 4641-4646
  • Peer Reviewed
• [Journal Article] Recent progress in the drug discovery of non-peptidic BACE1 inhibitors (2009)
  • Author(s): Y. Hamada, Y. Kiso
  • Journal Title: Expert Opinion on Drug Discovery 4 Pages: 391-416
  • Peer Reviewed
• [Journal Article] Structure of HIV-1 protease in complex with potent inhibitor KNI-272 determined by high resolution X-ray and neutron crystallograhy. (2009)
  • Author(s): Motoyasu Adachi
  • Journal Title: Proceedings of National Academy of Science USA 106 Pages: 4641-4646
  • Peer Reviewed
• [Journal Article] Controlled production of Alzheimer's amyloid β peptide from a photo-triggered, water-soluble precursor "click peptide" (2008)
  • Author(s): A. Taniguchi, M. Skwarczynski, Y. Sohma, T. Nagano, T. Okada, K. Ikeda, H. Prakash, H. Mukai, Y. Hayashi, T. Kimura, S. Hirota, K. Matsuzaki, Y. Kiso
  • Journal Title: Chem Bio Chem 9(18) Pages: 3055-3065
  • Peer Reviewed
• [Journal Article] Antimalarial activity enhancement in hydroxymethylcarbonyl (HMC) isostere-based dipeptidomimetics targeting malarial aspartic protease plasmepsin (2008)
  • Author(s): K. Hidaka, T. Kimura, A.J. Ruben, T. Uemura, M. Kamiya, A. Kiso, T. Okamoto, Y. Tsuchiya, Y. Hayashi, E. Freire, Y. Kiso
  • Journal Title: Bioorg. Med. Chem 16(23) Pages: 10049-10060
  • Peer Reviewed
• [Journal Article] Isopeptide method : Development of S-acyl isopeptide method for the synthesis of difficult sequence-containing peptides (2008)
  • Author(s): T. Yoshiya, N. Ito, T. Kimura, Y. Kiso
  • Journal Title: J. Peptide Sci 14(11) Pages: 1203-1208
  • Peer Reviewed
• [Journal Article] Design of potent aspartic protease inhibitors to treat various diseases (2008)
  • Author(s): J.-T. Nguyen, Y. Hamada, T. Kimura, Y. Kiso
  • Journal Title: Arch. Pharm. Chem. Life Sci 341(9) Pages: 523-535
  • Peer Reviewed
• [Journal Article] Locking the two ends of tetrapeptidic HTLV-1 protease inhibitors inside the enzyme (2008)
  • Author(s): M. Zhang, J.-T. Nguyen, H. Kumada, T. Kimura, M. Cheng, Y. Hayashi, Y. Kiso
  • Journal Title: Bioorg. Med. Chem 16(14) Pages: 6880-6890
  • Peer Reviewed
• [Journal Article] Development of broadspectrum halomethyl ketone inhibitors against coronavirus main protease 3CLpro (2008)
  • Author(s): U. Bacha, J. Barrila, S. B. Gabelli, Y. Kiso, L. M. Amzel, E. Freire
  • Journal Title: Chem. Biol. Drug Design 72(7) Pages: 34-49
  • Peer Reviewed
• [Journal Article] Design, synthesis and biophysical properties of a helical As1-42 analog : inhibition of fibrillogenesis and cytotoxicity (2008)
  • Author(s): K. Matsuzaki, T. Okada, M. Tsukuda ; K. Ikeda ; Y. Sohma ; Y. Chiyomori ; A. Taniguchi ; S. Nakamura ; N. Ito ; Y. Hayashi ; Y. Kiso
  • Journal Title: Biochem. Biophys. Res. Commun 371(4) Pages: 777-780
  • Peer Reviewed
• [Journal Article] Combination of non-natural D-amino acid derivatives and allophenylnorstatine-dimethyl-thioproline scaffold in HIV protease inhibitors have high efficacy in Mutant HIV (2008)
  • Author(s): S. Nakatani, K. Hidaka, E. Ami, K. Nakahara, A. Sato, J.-T. Nguyen, Y. Hamada, Y. Hori, N. Ohnishi, A. Nagai, T. Kimura, Y. Hayashi, Y. Kiso
  • Journal Title: J. Med. Chem 51(10) Pages: 2992-3004
  • Peer Reviewed
• [Journal Article] Synthesis and activity of tetrapeptidic HTLV-I protease inhibitors possessing different P3-cap moieties (2008)
  • Author(s): M. Zhang, J. Nguyen, H. Kumada, T. Kimura, M. Cheng, Y. Hayashi, Y. Kiso
  • Journal Title: Bioorg. Med. Chem 16(10) Pages: 5795-5802
  • Peer Reviewed
• [Journal Article] Novel nonpeptidic and small-sized BACE1 inhibitors (2008)
  • Author(s): Y. Hamada, H. Ohta, N. Miyamoto, R. Yamaguchi, A. Yamani, K. Hidaka, T. Kimura, K. Saito, Y. Hayashi, S. Ishiura, Y. Kiso
  • Journal Title: Bioorg. Med. Chem. Lett 18(5) Pages: 1654-1658
  • Peer Reviewed
• [Journal Article] BACE1 inhibitors : Optimization by replacing the P1' residue with non-acidic moiety (2008)
  • Author(s): Y. Hamada, H. Abdel-Rahman, A. Yamani, J.-T. Nguyen, K. Hidaka, T. Kimura, Y. Hayashi, K. Saito, S. Ishiura, Y. Kiso
  • Journal Title: Bioorg. Med. Chem. Lett 18(5) Pages: 1649-1653
  • Peer Reviewed
• [Journal Article] Truncation and non-natural amino acid substitution studies on HTLV-I protease hexapeptidic inhibitors (2008)
  • Author(s): J-T. Nguyen, M. Zhang, H. Kumada, A. Itami, K. Nishiyama, T. Kimura, M. Cheng, Y. Hayashi, Y. Kiso
  • Journal Title: Bioorg. Med. Chem. Lett 18(1) Pages: 366-370
  • Peer Reviewed
• [Journal Article] Combination of Non-naturalD-amino acid derivatives and allophenylnorstatine-dimethylthioproline scaffold in HIV proteaseinhibitors have high efficacy in mutant HIV (2008)
  • Author(s): S. Nakatani, T. Kimura, Y. Kiso, 他10名
  • Journal Title: J.Med.Chem. 51 Pages: 2992-3004
  • Peer Reviewed
• [Journal Article] Combination of non-natural D-amino acid derivatives and Allophenylnorstatine-dimethylthioproline scaffold in HIV portease inhibitors have high efficacy in mutant HIV. (2008)
  • Author(s): Shingo Nakatani
  • Journal Title: Journal of Medicinal Chemistry 51 Pages: 2992-3004
  • Peer Reviewed
• [Journal Article] Locking the two ends of tetrapeptidic HTLV-1 protease inhibitors inside the enzyme. (2008)
  • Author(s): Meihui Zhang
  • Journal Title: Bioorganic Medicinal Chemistry Letters 16 Pages: 6880-6890
  • Peer Reviewed
• [Journal Article] Novel non-peptidic and small-sized BACE1 inhibitors (2008)
  • Author(s): Yoshio Hamada
  • Journal Title: Bioorganic Medicinal Chemistry Letters 18 Pages: 1654-1658
  • Peer Reviewed
• [Journal Article] "O-Acyl isopeptide method" for peptide synthesis : Solvent effects in the synthesis of As1-42 isopeptide using "O-acyl isodipeptide unit" (2007)
  • Author(s): A. Taniguchi, T. Yoshiya, N. Abe, F. Fukao, Y. Sohma, T. Kimura, Y. Hayashi, Y. Kiso
  • Journal Title: J. Peptide Sci 13(12) Pages: 868-874
  • Peer Reviewed
• [Journal Article] プロテアーゼ阻害剤 : 蛋白質核酸酵素 (2007)
  • Author(s): 濱田芳男、木曽良明、長野哲雄、長田裕之、菊地和也、上杉志成編
  • Journal Title: 増刊号「ケミカルバイオロジー」 Pages: 1702-1707
  • Peer Reviewed
• [Journal Article] アルツハイマー病はどこまで克服されたか-創薬・治療の最前線を聞く (2007)
  • Author(s): 木曽良明
  • Journal Title: 平成19年版人類とバイオ-知の大競争時代をいかに勝ち抜くか-(東京テクノ・フォーラム21編) Pages: 381-402
• [Journal Article] Synthesis and antiviral property of allophenylnorstatine-based HIV protease inhibitors incorporating D-cysteine derivatives as P2/P3 moieties. Bioorg (2007)
  • Author(s): E. Ami, K. Nakahara, A. Sato, J.-T. Nguyen, K. Hidaka, Y. Hamada, S. Nakatani, T. Kimura, Y. Hayashi, Y. Kiso
  • Journal Title: Med. Chem. Lett 17(15) Pages: 4213-4217
  • Peer Reviewed
• [Journal Article] Compensating enthalpic and entropic changes hinder binding affinity optimization (2007)
  • Author(s): V. Lafont, A. A. Armstrong, H. Ohtaka, Y. Kiso, L. M. Amzel, E. Freire
  • Journal Title: Chemical Biology & Drug Design 69(6) Pages: 413-422
  • Peer Reviewed
• [Journal Article] Chipping at large, potent human T-cell leukemia virus type 1 protease inhibitors to uncover smaller, equipotent inhibitors (2007)
  • Author(s): T. Kimura, J.-T. Nguyen, H. Maegawa, K. Nishiyama, Y. Arii, Y. Matsui, Y. Hayashi, Y. Kiso
  • Journal Title: Bioorg. Med. Chem. Lett. 17(12) Pages: 3276-3280
  • Peer Reviewed
• [Journal Article] "O-Acyl isopeptide method" for peptide synthesis : synthesis of forty kinds of "O-acyl isodipeptide unit" Boc-Ser/Thr(Fmoc-Xaa)-OH (2007)
  • Author(s): T. Yoshiya, A. Taniguchi, Y. Sohma, F. Fukao, S. Nakamura, N. Abe, N. Ito, M. Skwarczynski, T. Kimura, Y. Hayashi, Y. Kiso
  • Journal Title: Org. Biomol. Chem 5(11) Pages: 1720-1730
  • Peer Reviewed
• [Journal Article] Additional interaction of allophenylnorstatine containing tripeptidomimetics with malarial aspartic protease plasmepsin II (2007)
  • Author(s): K. Hidaka, T. Kimura, Y. Tsuchiya, M. Kamiya, A. J. Ruben, E. Freire, Y. Hayashi, Y. Kiso
  • Journal Title: Bioorg. Med. Chem. Lett 17(11) Pages: 3048-3052
  • Peer Reviewed
• [Journal Article] Development of "O-Acyl Isopeptide Method" (2007)
  • Author(s): Y. Sohma, T. Yoshiya, A. Taniguchi, T. Kimura, Y. Hayashi, Y. Kiso
  • Journal Title: Biopolymers Peptide Science 88(2) Pages: 253-262
  • Peer Reviewed
• [Journal Article] Design and synthesis of BACE1 inhibitors containing a novel norstatine derivative (2R, 3R)-3-amino-2-hydroxy-4-(phenylthio) butyric acid (2007)
  • Author(s): Z. Ziora, S. Kasai, K. Hidaka, A. Nagamine, T. Kimura, Y. Hayashi, Y. Kiso
  • Journal Title: Bioorg. Med. Chem. Lett 17(6) Pages: 1629-1633
  • Peer Reviewed
• [Journal Article] Additional interaction of allophenylnorstatine-containing tripeptidomimetics with malarial aspartic protease plasmepsin II (2007)
  • Author(s): Koushi Hidaka
  • Journal Title: Bioorganic Medicinal Chemistry Letters 17 Pages: 3048-3052
  • Peer Reviewed
• [Journal Article] Chipping at large,potent human T-cell leukemia virus type 1 protease inhibitors to uncover smaller,equipotent inhibitors (2007)
  • Author(s): Tooru Kimura
  • Journal Title: Bioorganic Medicinal Chemistry Letters 17 Pages: 3276-3280
  • Peer Reviewed
• [Journal Article] Design and synthesis of BACE1 inhibitors containing a novel norstatine derivative (2R, 3R)-3-amino-2-hydroxy-4-(phenylthio)butyric acid. (2007)
  • Author(s): Zyta Ziora
  • Journal Title: Bioorganic Medicinal Chemistry Letters 17・6 Pages: 1629-1633
• [Journal Article] "Click peptide" : a novel "O-acyl isopeptide method" for peptide synthesis and chemical biology-oriented synthesis of amyloid β peptide analogues (2006)
  • Author(s): Y. Sohma, A. Taniguchi, T. Yoshiya, Y. Chiyomori, F. Fukao, S. Nakamura, M. Skwarczynski, T. Okada, K. Ikeda, Y. Hayashi, T. Kimura, S. Hirota, K. Matsuzaki, Y. Kiso
  • Journal Title: J. Peptide Science 12(12) Pages: 823-828
  • Peer Reviewed
• [Journal Article] Views on amyloid hypothesis and secretase inhibitors for treating Alzheimer's disease : Progress and problems (2006)
  • Author(s): J. Nguyen, A. Yamani, Y. Kiso
  • Journal Title: Current Pharm. Des 12(33) Pages: 4295-4312
  • Peer Reviewed
• [Journal Article] Chemical biology-oriented synthesis of Alzheimer's disease-related amyloid β peptide (Aβ) analogues based on the "O-acyl isopeptide method" (2006)
  • Author(s): Y. Sohma, Y. Kiso : "Click peptide"
  • Journal Title: Chem-Bio Chem 7(10) Pages: 1549-1557
  • Peer Reviewed
• [Journal Article] "O-Acyl isopeptide method" : racemization- free segment condensation in solid phase peptide synthesis (2006)
  • Author(s): T. Yoshiya, Y. Sohma, T. Kimura, Y. Hayashi, Y. Kiso
  • Journal Title: Tetrahedron Lett 47(45) Pages: 7905-7909
  • Peer Reviewed
• [Journal Article] Synthesis of glutamic acid and glutamine peptides possessing a trifluoromethyl ketone group as SARS-CoV 3CL protease inhibitors (2006)
  • Author(s): M. O. Sydnes, Y. Hayashi, V. K. Sharma, T. Hamda, U. Bacha, J. Barrila, E. Freire, Y. Kiso
  • Journal Title: Tetrahedron 62(36) Pages: 8601-8609
  • Peer Reviewed
• [Journal Article] β-Secretase inhibitors : Modification at the P4 position and improvement of inhibitory activity in cultured cell (2006)
  • Author(s): Y. Hamada, N. Igawa, H. Ikari, Z. Ziora, J.-T. Nguyen, A. Yamani, K. Hidaka, T. Kimura, K. Saito, Y. Hayashi, M. Ebina, S. Ishiura, Y. Kiso
  • Journal Title: Bioorg. Med. Chem. Lett 16(16) Pages: 4354-4359
  • Peer Reviewed
• [Journal Article] 今エイズ薬研究はどうなっているか (2006)
  • Author(s): 日高興士, 木曽良明
  • Journal Title: 化学 61(5) Pages: 25-29
  • NAID: 40007270962
• [Journal Article] Design and synthesis of potent s-secretase (BACE1) inhibitors with P1' carboxylic acid bioisosteres (2006)
  • Author(s): T. Kimura, Y. Hamada, M. Stochaj, H. Ikari, A. Nagamine, H. Abdel-Rahman, N. Igawa, K. Hidaka, J.-T. Nguyen, K. Saito, Y. Hayashi, Y. Kiso
  • Journal Title: Bioorg. Med. Chem. Lett 16(9) Pages: 2380-2386
  • Peer Reviewed
• [Journal Article] "O-Acyl isopeptide method" for the efficient synthesis of difficult sequence-containing peptides : use of "O-acyl isodipeptide unit" (2006)
  • Author(s): Y. Sohma, A. Taniguchi, M. Skwarczynski, T. Yoshiya, F. Fukao, T. Kimura, Y. Hayashi, Y. Kiso
  • Journal Title: Tetrahedron Lett 47(18) Pages: 3013-3017
  • Peer Reviewed
• [Journal Article] アルツハイマー病の治療薬をつくる (2006)
  • Author(s): 石浦章一, 木曽良明
  • Journal Title: 日経サイエンス 36(4) Pages: 64-69
  • Peer Reviewed
• [Journal Article] Views onamyloid hyupothesis and secretase inhibitors fortreating Alzheimer's disease : Progress andproblems (2006)
  • Author(s): J.-T. Nguyen, A. Yamani, Y. Kiso
  • Journal Title: Current Pharmaceutical Design 12 Pages: 4295-4312
  • Peer Reviewed
• [Journal Article] "Click peptide" : chemicalbiology-oriented synthesis of Alzheimer's disease-related amyloid β peptide(Aβ)analogues based on the"O-acyl isopeptide method" (2006)
  • Author(s): Y. Sohma, Y. Kiso
  • Journal Title: ChemBioChem 7 Pages: 1549-1557
  • Peer Reviewed
• [Journal Article] アルツハイマー病の治療薬をつくる. (2006)
  • Author(s): 石浦章一
  • Journal Title: 日経サイエンス 36・4 Pages: 64-69
• [Journal Article] 今エイズ薬研究はどうなっているか. (2006)
  • Author(s): 日高興士
  • Journal Title: 化学 61・5 Pages: 25-29
• [Journal Article] β-Secretase inhibitors : Modification at the P4 position and improvement of inhibitory activity in cultured cell. (2006)
  • Author(s): Yoshio Hamada
  • Journal Title: Bioorganic Medicinal Chemistry Letters 16・16 Pages: 4354-4359
• [Journal Article] Synthesis of glutamic acid and glutamine peptides possessing a trifluoromethyl ketone group as SARS-CoV 3CL protease inhibitors. (2006)
  • Author(s): Magne O. Sydnes
  • Journal Title: Tetrahedron 62・36 Pages: 8601-8609
• [Journal Article] Views on amyloid hypothesis and secretase inhibitors for treating Alzheimer's disease : Progress and problems. (2006)
  • Author(s): Jeffrey-Tri Nguyen
  • Journal Title: Current Pharmaceutical Design 12・33 Pages: 4295-4312
• [Presentation] Defying difficult diseases : design and synthesis of protease inhibitors, prodrug forms and click peptides. PSJ-AAPS Joint Symposium : New Trends of Medicinal Chemistry (2009)
  • Author(s): Y. Kiso
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] P2位に2, 6-ピリジンジカルボキサミド骨格を有する低分子型BACE1阻害剤の構造活性相関研究 (2008)
  • Author(s): 〓田芳男
  • Organizer: 第27回メディシナルケミストリーシンポジウム
  • Place of Presentation: メルパルク大阪、大阪市
  • Year and Date: 2008-11-26
• [Presentation] 生物分子システムを基盤とする創薬科学 (2008)
  • Author(s): 木曽良明
  • Organizer: 統合創薬科学フロンティアシンポジウム~伝承薬から生物分子システムまでを基盤として~
  • Place of Presentation: 京都
• [Presentation] Defying difficult diseases : peptide chemistry in medicinal science (2008)
  • Author(s): Y. Kiso
  • Organizer: 45th Japanese Peptide Symposium
  • Place of Presentation: Tokyo, Japan
• [Presentation] Effect of dipeptidomimetics on malaria parasite proliferation inhibition targeting plasmepsin (2008)
  • Author(s): K. Hidaka, T. Kimura, T. Uemura, A. J. Ruben, E. Freire, Y. Kiso
  • Organizer: 45th Japanese Peptide Symposium
  • Place of Presentation: Tokyo, Japan
• [Presentation] SAR study of BACE1 inhibitors containing pyridine derivatives (2008)
  • Author(s): H. Ohta, Y. Hamada, N. Miyamoto, R. Yamaguchi, A. Yamani, K. Hidaka, T. Kimura, K. Saito, S. Ishiura, Y. Kiso
  • Organizer: 45th Japanese Peptide Symposium
  • Place of Presentation: Tokyo, Japan
• [Presentation] BACE1阻害剤の設計-ペプチドから非ペプチドへ (2008)
  • Author(s): 濱田芳男、大田博子、宮本奈緒子、山口亮司、A. Yamani、日高興士、木村徹、齋藤一樹、石浦章一、木曽良明
  • Organizer: 第13回病態と治療におけるプロテアーゼとインヒビター学会
  • Place of Presentation: 吹田
• [Presentation] Synthesis of transition-state mimic protease inhibitors and click peptides based on O-N acyl shift (2008)
  • Author(s): Y. Kiso
  • Organizer: 10th Chinese International Peptide Symposium(CPS-2008)
  • Place of Presentation: Xi'an, China
• [Presentation] β-セクレターゼをターゲットとするアミロイド生成阻害薬開発の展望 (2008)
  • Author(s): 木曽良明
  • Organizer: 日本薬学会第128年会シンポジウム「アルツハイマー病の画期的創薬」
  • Place of Presentation: 横浜
• [Presentation] 難病克服を目指した生物分子を基盤とする創薬科学 (2008)
  • Author(s): 木曽良明
  • Organizer: 第1回熊本創薬シンポジウム
  • Place of Presentation: 熊本
• [Presentation] Defying difficult diseases : Synthesisof peptidomimetic protease inhibitors, prodrugforms and click peptides (2007)
  • Author(s): Y. Kiso
  • Organizer: Modern Solid Phase Peptide Synthesis &amp; Its Applications
  • Place of Presentation: Port Douglas, Australia
  • Year and Date: 2007-10-17
• [Presentation] Challenging difficult diseases:protease inhibitors and prodrug forms (2007)
  • Author(s): Y.Kiso
  • Organizer: 2nd European Conference on Chemistry for Life Sciences
  • Place of Presentation: Wroclaw,Poland
  • Year and Date: 2007-09-04
• [Presentation] Click peptide : pHor photo-triggered in situ production of Alzheimer's disease-related amyloid β peptide 1-42. 4th Takeda Sci. Found. Symp. PharmaSciences (2007)
  • Author(s): A. Taniguchi, Y. Sohma, Y. Hayashi, S. Hirota, K. Matsuzaki, Y. Kiso
  • Organizer: On the Frontiers of Chem. Biol
  • Place of Presentation: Tokyo
• [Presentation] HIV protease and malarial plasmepsin inhi bitors with hydroxylmethylcarbonyl isostere (2007)
  • Author(s): K. Hidaka, T. Kimura, Y. Tsuchiya, M. Kamiya, E. Freire, B. M. Dunn, Y. Hayashi, Y. Kiso
  • Organizer: 5th General Meeting of the International Proteolysis Society
  • Place of Presentation: Patras, Greece
• [Presentation] Defying difficult diseases : Synthesis of peptidomimetic protease inhibitors, prodrug forms and click peptides (2007)
  • Author(s): Y. Kiso
  • Organizer: Modern Solid Phase Peptide Synthesis & Its Applications
  • Place of Presentation: Port Douglas, Australia
• [Presentation] Challenging difficult diseases : protease inhibitors and prodrug forms (2007)
  • Author(s): Y. Kiso
  • Organizer: 2nd European Conference on Chemistry for Life Sciences
  • Place of Presentation: Wroclaw, Poland
• [Presentation] Challenging difficult diseases : synthesis of protease inhibitors and click peptides (2007)
  • Author(s): Y. Kiso
  • Organizer: The 6th International Symposium on Frontiers in Protein Chemistry and Biotechnology (ISFPCB'07)
  • Place of Presentation: Changchun, China
• [Presentation] Non-peptidic small-sized BACE1 inhibitors : optimazation based on the docked inhibitor's conformer in BACE1 (2007)
  • Author(s): Y. Hamada, N. Miyamoto, R. Yamaguchi, A. Yamani, K. Hidaka, H. Kumada, T. Kimura, K. Saito, Y. Hayashi, S. Ishiura, Y. Kiso
  • Organizer: 20th American Peptide Symposium : Peptides for Youth
  • Place of Presentation: Montreal, Canada
• [Presentation] Defying difficult diseases : peptidomimetic protease inhibitors, prodrug forms and click peptides (2007)
  • Author(s): Y. Kiso
  • Organizer: First Indian Peptide Symposium
  • Place of Presentation: Hyderabad, India
• [Presentation] Challenging difficult diseases : peptide mimetic inhibitors and click peptides (2006)
  • Author(s): Y. Kiso
  • Organizer: 10th Korean Peptide Symposium Frontiers in Peptide Science
  • Place of Presentation: Korea,Seoul
  • Year and Date: 2006-11-12
• [Presentation] Application of intramolecular migration reaction in peptide chemistry to chemical biology based on "click peptide", and chemical pharmaceutics (2006)
  • Author(s): Y. Hayashi, Y. Sohma, A. Taniguchi, M. Skwarczynski, T. Kimura, Y. Kiso
  • Organizer: The 11th Akabori Conf. 2006Japanese-German Symp. Peptide Sci
  • Place of Presentation: Kloster Banz, Germany
• [Presentation] Novel thio-derivative of phenylnorstatine and its application to the BACE1 inhibitors design (2006)
  • Author(s): Z. Ziora, S. Kasai, K. Hidaka, A. Nagamine, T. Kimura, Y. Hayashi, Y. Kiso
  • Organizer: 29th European Peptide Symposium
  • Place of Presentation: Gdansk, Poland
• [Presentation] Defying difficult diseases : design of protease inhibitors and prodrug forms (2006)
  • Author(s): Y. Kiso
  • Organizer: ICOB-5 & ISCNP-25 IUPAC International Conference on Biodiversity and Natural Products
  • Place of Presentation: Kyoto, Japan
• [Presentation] Challenging intractable diseases : protease inhibitors and O-N acyl migration-type prodrug forms (2006)
  • Author(s): Y. Kiso
  • Organizer: 9th Chinese International Peptide Symposium (CPS-9)-New Age of Peptide Biology and Chemistry
  • Place of Presentation: Shanghai, China
• [Presentation] Substrate transition-state mimetic inhibitors and prodrug forms using O-N intramolecular acyl migration (2006)
  • Author(s): Y. Kiso
  • Organizer: 7th Tetrahedron Symposium. Challenges in Organic Chemistry
  • Place of Presentation: Kyoto, Japan
• [Book] Wiley Encyclopedia of Chemical Biology(ed. Tadhg P. Begley) (2009)
  • Author(s): Y. Kiso, A. Taniguchi, Y. Sohma
  • Publisher: Click peptides : design and applications
• [Book] Click peptides : design and applications (2009)
  • Author(s): Y. Kiso, A. Taniguchi, Y. Sohma
  • Publisher: Wiley Encyclopedia of Chemical Biology(Ed.T.P.Begley)
• [Book] Wiley Encyclopedia of Chemical Biology (2009)
  • Author(s): Yoshiaki Kiso
  • Publisher: Wiley & Sons Inc.
• [Book] 化学フロンティア19, 創薬をめざす有機合成戦略-進化する医薬品づくり(宍戸宏造、新藤充編) (2007)
  • Author(s): 木曽良明、日高興士
  • Publisher: ペプチドと創薬研究
• [Book] 遺伝子医学MOOK, 8「ペプチドと創薬」 (2007)
  • Author(s): 木曽良明、濱田芳男
  • Publisher: プロテアーゼインヒビターからの創薬
• [Book] 化学フロンティア19.創薬をめざす有機合成戦略-進化する医薬品づくり (2007)
  • Author(s): 木曽 良明
  • Publisher: 化学同人
• [Remarks] 新聞掲載 : 2009年3月10日「HIV増殖の必須たんぱく質全原子構造を解明」などの見出しで、HIVプロテアーゼとKNI-272の複合体の構造解明研究が日本経済新聞、京都新聞などの新聞に掲載された。
• [Remarks] 新聞掲載 : 2009年3月10日「HIV増殖の必須たんぱく質全原子構造を解明」などの見出しで、HIVプロテアーゼとKNI-272の複合体の構造解明研究が日本経済新聞、京都新聞などの新聞に掲載された。
• [Patent(Industrial Property Rights)] βセクレターゼ阻害活性を有する新規化合物 (2007)
  • Inventor(s): 木曽良明
  • Industrial Property Rights Holder: 木曽良明
  • Industrial Property Number: 2007-164845
  • Filing Date: 2007-06-22
• [Patent(Industrial Property Rights)] Preparation of 3-amino-2-hydroxybutanamide deriva-tives as β-secretase inhibitors (2006)
  • Inventor(s): Yoshiaki Kisoほか
  • Industrial Property Rights Holder: 大日本住友製薬
  • Filing Date: 2006-08-31
  • Acquisition Date: 2007-03-15
• [Patent(Industrial Property Rights)] βセクレターゼ阻害活性を有する新規化合物
  • Inventor(s): 木曽良明
  • Industrial Property Rights Holder: 木曽良明
  • Industrial Property Number: 2007-164845