Design and Medicinal Chemistry Research on Therapeutics ofDifficult Diseases based on Molecular Recognition

• Project/Area Number: 21249007
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Nagahama Institute of Bio-Science and Technology (2011-2012); Kyoto Pharmaceutical University (2009-2010)
• Principal Investigator: KISO Yoshiaki 長浜バイオ大学, バイオサイエンス学部, 教授 (40089107)
• Co-Investigator(Kenkyū-buntansha): KIMURA Tooru 京都薬科大学, 薬学部, 准教授 (70204980) ; SOHMA Youhei 東京大学, 薬学研究科(研究院), 研究員 (10565518) ; MUKAI Hidehito 長浜バイオ大学, バイオサイエンス学部, 准教授 (20251027) ; HIDAKA Koushi 神戸学院大学, 薬学部, 講師 (30445960)
• Project Period (FY): 2009 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥46,410,000 (Direct Cost: ¥35,700,000、Indirect Cost: ¥10,710,000); Fiscal Year 2012: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000); Fiscal Year 2010: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2009: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
• 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 / ss-セクレターゼ / クリプタイド / クリックペプチド / 酵素阻害剤 / β-セクレターゼ

Research Abstract

In order to develop therapeutics of difficult diseases based on molecular recognition, design of protease inhibitors based on the substrate transition state concept, elucidation of pathological mechanism of Alzheimer’s disease, its application to development of the therapeutics, identification of new physiologically active peptide, cryptides hidden in the protein sequences, and analysis of their signal transduction mechanism were carried out.

Research Products

• [Journal Article] Comparative properties of Aβ1-42, Aβ11-42, and [Pyr^<11>]Aβ11-42 generated from O-acyl isopeptides (2013)
  • Author(s): 相馬洋平
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 23巻 Issue: 5 Pages: 1326-1329
  • DOI: 10.1016/j.bmcl.2012.12.082
  • Peer Reviewed
• [Journal Article] Design and synthesis of new tripeptide-type SARS-CoV 3CL protease inhibitors containing an electrophilic arylketone moiety (2013)
  • Author(s): S. Konno, P. Thanigaimalai, Shen-En Chen, Ernesto Freire, Y. Hayashi, 他9名
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 21 Issue: 2 Pages: 412-424
  • DOI: 10.1016/j.bmc.2012.11.017
  • Peer Reviewed
• [Journal Article] Advances in the identification of beta-secretase inhibitors. (2013)
  • Author(s): Yoshio Hamada
  • Journal Title: Expert Opinion on Drug Discovery Volume: 8 Issue: 6 Pages: 1-23
  • DOI: 10.1517/17460441.2013.784267
  • Peer Reviewed
• [Journal Article] Synthesis of O-Acyl Isopeptides. (2013)
  • Author(s): Youhei Sohma
  • Journal Title: Chemical Record Volume: 13 Issue: 2 Pages: 218-223
  • DOI: 10.1002/tcr.201200023
  • Peer Reviewed
• [Journal Article] Tripeptidic BACE1 inhibitors devised by in-silico conformational structure- based design. (2012)
  • Author(s): Yoshio Hamada, Harichandra D. Tagad, Yoshinori Nishimura, Shoichi Ishiura, Yoshiaki Kiso
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 22(2) Issue: 2 Pages: 1130-1135
  • DOI: 10.1016/j.bmcl.2011.11.102
  • Peer Reviewed
• [Journal Article] BACE1 inhibitor peptides: Can an infinitely small kcat value turn the substrate of an enzyme into its inhibitor? (2012)
  • Author(s): Yoshio Hamada, Shoichi Ishiura, Yoshiaki Kiso
  • Journal Title: ACS Med Chem Lett. Volume: 3(3) Issue: 3 Pages: 193-197
  • DOI: 10.1021/ml2002373
  • Peer Reviewed
• [Journal Article] Isolation and Identification of Novel Neutrophil-Activating Cryptides Hidden in Mitochondrial Cytochromec. (2012)
  • Author(s): Yoshinori Hokari, Tetsuo Seki, Hiroko Nakano, Yuko Matsuo, Akiyoshi Fukarnizu, Eisukc Munekata, Yoshiaki Kiso, Hidehito Mukai
  • Journal Title: Protein Peptide Letters Volume: 19 Issue: 6 Pages: 680-687
  • DOI: 10.2174/092986612800494048
  • Peer Reviewed
• [Journal Article] The application of bioisosteres in drug design for novel drug discovery: focusing on acid protease inhibitors. (2012)
  • Author(s): Yoshio Hamada, Yoshiaki Kiso
  • Journal Title: Expert Opinion on Drug Discovery Volume: 7(10) Issue: 10 Pages: 903-922
  • DOI: 10.1517/17460441.2012.712513
  • Peer Reviewed
• [Journal Article] The application of bioisosteres in drug design for novel drug discovery: focusing on acid protease inhibitors. (2012)
  • Author(s): Yoshio Hamada
  • Journal Title: Expert Opinion on Drug Discovery Volume: 7 Pages: 903-922
  • Peer Reviewed
• [Journal Article] 'Click peptide' using production of monomer Ab from the O-acyl isopeptide: Application to assay system of aggregation inhibitors and cellular cytotoxicity. (2011)
  • Author(s): Youhei Sohma, Yuta Hirayama, AtsuhikoTaniguchi, Hidehito Mukai, Yoshiaki Kiso
  • Journal Title: Bioorg. Med. Chem. Volume: 19 Issue: 5 Pages: 1729-1733
  • DOI: 10.1016/j.bmc.2011.01.021
  • Peer Reviewed
• [Journal Article] Maintaining potent HTLV-I protease inhibition without the P3-cap moiety in small tetrapeptidic inhibitors. (2011)
  • Author(s): Jeffrey-Tri Nguyen, Keiko Kato, Henri-Obadja Kumada, Koushi Hidaka, Tooru Kimura, Yoshiaki Kiso
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 21 Issue: 6 Pages: 1832-1837
  • DOI: 10.1016/j.bmcl.2011.01.048
  • Peer Reviewed
• [Journal Article] Mitocryptide-2, a neutrophil-activating cryptide, is a specific endogenous agonist for formyl-peptide receptor-like 1. Biochem. (2011)
  • Author(s): Tesuo Seki, Akiyoshi Fukamizu, Yoshiaki Kiso, Hidehito Mukai
  • Journal Title: Biophys. Res. Commun. Volume: 404(1) Issue: 1 Pages: 482-487
  • DOI: 10.1016/j.bbrc.2010.12.007
  • Peer Reviewed
• [Journal Article] "Click Peptide" Concept: O-Acyl Isopeptide of Islet Amyloid Poly- peptide As a non-aggregative precursor molecule. (2011)
  • Author(s): Taku Yoshiya, Ayano Higa, Naoko Abe, Fukue Fukao, Tomomi Kuruma, Youhei Sohma, Yoshiaki Kiso
  • Journal Title: ChemBioChem. Volume: 12(8) Issue: 8 Pages: 1216-1222
  • DOI: 10.1002/cbic.201100025
  • Peer Reviewed
• [Journal Article] Design and synthesis of several small-size HTLV-I protease inhibitors with different hydrophilicity profiles. (2011)
  • Author(s): Jeffrey-Tri Nguyen, Keiko Kato, Koushi Hidaka, Henri-Obadja Kumada, Tooru Kimura, Yoshiaki Kiso
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 21 Issue: 8 Pages: 2425-2429
  • DOI: 10.1016/j.bmcl.2011.02.066
  • Peer Reviewed
• [Journal Article] The E22SS-type mutant of amyloid SS peptide (ASS) adopts distinct selfassembly mechanisms from wild- type ASS. (2011)
  • Author(s): Youhei Sohma, Hui Wang, Atsuhiko Taniguchi, Yuta Hirayama, Taeko Kakizawa, Hidehito Mukai, Yoshiaki Kiso
  • Journal Title: Bioorg. Med. Chem. Volume: 19 Issue: 12 Pages: 3787-3792
  • DOI: 10.1016/j.bmc.2011.04.056
  • Peer Reviewed
• [Journal Article] Crystal structure of the free and inhibited plasmepsin I from Plasmodium falciparum. (2011)
  • Author(s): Prasenjit Bhaumik, Yasumi Horimoto, Huogen Xiao, Alexander Wlodawer, Yoshiaki Kiso, Rickey Y. Yada, Alla Gustchina
  • Journal Title: J. Structural Biol. Volume: 175(1) Issue: 1 Pages: 73-84
  • DOI: 10.1016/j.jsb.2011.04.009
  • Peer Reviewed
• [Journal Article] Development of L40I HTLV-I protease inhibition assay using novel fluorogenic and chromogenic substrate. (2011)
  • Author(s): Henri-Obadja Kumada, Jeffrey-Tri Nguyen, Keiji Nishiyama, Taeko Kakizawa, Yasuhiro Arii, Koushi Hidaka, Tooru Kimura, Yoshio Hayashi, Yoshiaki Kiso
  • Journal Title: J. Peptide Science Volume: 17(8) Issue: 8 Pages: 569-575
  • DOI: 10.1002/psc.1375
  • Peer Reviewed
• [Journal Article] Structure-guided design and synthesis of P1' position 1-phenylcycloalkyl-amine-derived pentapeptidic BACE1 inhibitors. (2011)
  • Author(s): Harichandra D. Tagad, Yoshio Hamada, Jeffrey-Tri Nguyen, Koushi Hidaka, Takashi Hamada, Youhei Sohma, Tooru Kimura, Yoshiaki Kiso
  • Journal Title: Bioorg. Med. Chem. Volume: 19 Issue: 17 Pages: 5238-5246
  • DOI: 10.1016/j.bmc.2011.07.002
  • Peer Reviewed
• [Journal Article] Structural insights into activation and inhibition of histo-aspartic protease (HAP) from Plasmodium falciparum. (2011)
  • Author(s): Prasenjit Bhaumik, Huogen Xiao, Koushi Hidaka, Alla Gustchin, Yoshiaki Kiso, Rickey Y. Yada, Alexander Wlodawer
  • Journal Title: Biochemistry. Volume: 50(41) Issue: 41 Pages: 8862-8879
  • DOI: 10.1021/bi201118z
  • Peer Reviewed
• [Journal Article] Synthesis of an O-acyl isopeptide by using native chemical ligation to efficiently construct a hydrophobic polypeptide. (2011)
  • Author(s): Youhei Sohma, Hitomi Kitamura, Hiroyuki Kawashima, Hironobu Hojo, Masayuki Yamashita, Kenichi Akaji, Yoshiaki Kiso
  • Journal Title: Tetrahedron Letters Volume: 52(52) Issue: 52 Pages: 7146-7148
  • DOI: 10.1016/j.tetlet.2011.10.116
  • NAID: 10030204148
  • Peer Reviewed
• [Journal Article] Mitocryptide-2, a neutrophil-activating cryptide, is a specific endogenous agonist for formyl-peptide receptor-like 1. (2011)
  • Author(s): Tetsuo Seki
  • Journal Title: Biochem.Biophys.Res.Comm. Volume: 404 Pages: 482-487
  • Peer Reviewed
• [Journal Article] Synthesis of the sphingolipid activator protein, saposin C, using an azido-protected O-acyl isopeptide as an aggregation-disrupting element. (2011)
  • Author(s): Hironobu Hojo
  • Journal Title: Tetrahedron Letters Volume: 52 Pages: 635-639
  • Peer Reviewed
• [Journal Article] Click peptide' using production of monomer Aβ from the O-acyl isopeptide : Application to assay system of aggregation inhibitors and cellular cytotoxicity. (2011)
  • Author(s): Youhei Sohma
  • Journal Title: Bioorg.Med.Chem. Volume: 19 Pages: 1729-1733
  • Peer Reviewed
• [Journal Article] Maintaining potent HTLV-I protease inhibition without the P3-cap moiety in small tetrapeptidic inhibitors. (2011)
  • Author(s): Jeffrey-Tri Nguyen
  • Journal Title: Bioorg.Med.Chem.Lett. Volume: 21 Pages: 1832-1837
  • Peer Reviewed
• [Journal Article] How much binding affinity can be gained by filling a cavity? (2010)
  • Author(s): Yuko Kawasaki, Eduardo E. Chufan, Virginie Lafont, Koushi Hidaka, Yoshiaki Kiso, L. Mario Amzel, Ernesto Freire
  • Journal Title: Chem.Biol. Drug Design Volume: 75(2) Issue: 2 Pages: 143-151
  • DOI: 10.1111/j.1747-0285.2009.00921.x
  • Peer Reviewed
• [Journal Article] Design of pentapeptidic BACE1 inhibitors with carboxylic acid bioisosteres at P1' and P4 positions. (2010)
  • Author(s): Harichandra D. Tagad, Yoshio Hamada, Jeffrey-Tri Nguyen, Takashi Hamada, Hamdy Abdel-Rahman, Abdellah Yamani, Ayaka Nagamine, Hayato Ikari, Naoto Igawa, Koushi Hidaka, Youhei Sohma, Tooru Kimura, Yo shiaki Kiso
  • Journal Title: Bioorg.Med. Chem. Volume: 18(9) Issue: 9 Pages: 3175-3186
  • DOI: 10.1016/j.bmc.2010.03.032
  • Peer Reviewed
• [Journal Article] Tetrapeptides, as small-sized peptidic inhibitors; synthesis and their inhibitory activity against (2010)
  • Author(s): Taeko Kakizawa, Koushi Hidaka, Daisuke Hamada, Ryoji Yamaguchi, Tsuyoshi Uemura, Hitomi Kitamura, Harichandra D. Tagad, Takashi Hamada, Zyta Ziora, Yoshio Hamada, Tooru Kimura, Yoshiaki Kiso
  • Journal Title: BACE1. J. Peptide Science Volume: 16 Issue: 6 Pages: 257-262
  • DOI: 10.1002/psc.1238
  • Peer Reviewed
• [Journal Article] Reversible modification of peptides containing the O-acyl iso-prolyl- seryl motif. (2010)
  • Author(s): Michael Beiswenger, Taku Yoshiya, Yoshiaki Kiso, Chiara Cabrele
  • Journal Title: J. Peptide Science Volume: 16 Pages: 303-308
  • Peer Reviewed
• [Journal Article] Crystal growth proce- dure of HIV-1 protease-inhibitor KNI-272 com-plex for neutron structural analysis at 1.9A re- solution. (2010)
  • Author(s): Noriko Shimizu, Shigeru Sugiyama, Mihoko Maruyama, Yoshinori Takahashi, Motoyasu Adachi, Taro Tamada, Koushi Hidaka, Yoshio Hayashi, Tooru Kimura, Yoshiaki Kiso, Hiroaki Adachi, Kazufumi Takano, Satoshi Murakami, Tsuyoshi Inoue, Ryota Kuroki, Yusuke, Mori, Hiroyoshi Matsumura
  • Journal Title: Crystal Growth Design Volume: 10 Issue: 6 Pages: 2990-2994
  • DOI: 10.1002/psc.1239
  • Peer Reviewed
• [Journal Article] Racemization- free synthesis of cyclic peptide by use of the O-acyl isopeptide method. (2010)
  • Author(s): Taku Yoshiya, Hiroyuki Kawashima, Yuka Hasegawa, Kazuhiro Okamoto, Tooru Kimura, Youhei Sohma, Yoshiaki Kiso
  • Journal Title: J. Peptide Science. Volume: 16(8) Issue: 8 Pages: 437-442
  • DOI: 10.1002/psc.1261
  • Peer Reviewed
• [Journal Article] Improvement of both plasmepsin inhibitory activity and Antimalarial activity by 2-aminoethylamino substitution. (2010)
  • Author(s): Takuya Miura, Koushi Hidaka, Tsuyoshi Uemura, Keisuke Kashimoto, Yuto Hori, Yuko Kawasaki, Adam J. Ruben, Ernesto Freire, Tooru Kimura, Yoshiaki Kiso
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 20(16) Issue: 16 Pages: 4836-4839
  • DOI: 10.1016/j.bmcl.2010.06.099
  • Peer Reviewed
• [Journal Article] Crystal structures of the inhibitor com- plexes of human T cell leukemia virus (HTLV-1) protease. (2010)
  • Author(s): Tadashi Satoh, Mi Li, Jeffrey-Tri Nguyen, Yo shiaki Kiso, Alla Gustchina, Alexander Wlo- dawer
  • Journal Title: J. Mol. Biol. Volume: 401 Issue: 4 Pages: 626-641
  • DOI: 10.1016/j.jmb.2010.06.052
  • Peer Reviewed
• [Journal Article] Design of pentapeptidic BACE1 inhibitors with carboxylic acid bioisosteres at P1' and P4 positions. (2010)
  • Author(s): Harichandra D.Tagad
  • Journal Title: Bioorg.Med.Chem. Volume: 18 Pages: 3175-3186
  • Peer Reviewed
• [Journal Article] Tetrapeptides, as small-sized peptidic inhibitors ; synthesis and their inhibitory activity against BACE1. (2010)
  • Author(s): Taeko Kakizawa
  • Journal Title: J.Peptide Science Volume: 16 Pages: 257-262
  • Peer Reviewed
• [Journal Article] Reversible modification of peptides containing the O-acyl iso-prolyl-seryl motif. (2010)
  • Author(s): Michael Beisswenger
  • Journal Title: J.Peptide Science Volume: 16 Pages: 303-308
  • Peer Reviewed
• [Journal Article] クリプタイドの発見と新しい生体情報伝達機構 (2010)
  • Author(s): 向井秀仁
  • Journal Title: 生化学 Volume: 82 Pages: 524-532
  • NAID: 10026900043
  • Peer Reviewed
• [Journal Article] Crystal growth procedure of HIV-1 protease-inhibitor KNI-272 complex for neutron structural analysis at 1.9A resolution. (2010)
  • Author(s): Noriko Shimizu
  • Journal Title: Crystal Growth & Design Volume: 10 Pages: 2990-2994
  • Peer Reviewed
• [Journal Article] Racemization-free synthesis of cyclic peptide by use of the O-acyl isopeptide method. (2010)
  • Author(s): Taku Yoshiya
  • Journal Title: J.Peptide Science Volume: 20 Pages: 4836-4839
  • Peer Reviewed
• [Journal Article] Crystal structures of the inhibitor complexes of human T cell leukemia virus (HTLV-1) protease. (2010)
  • Author(s): Tadashi Satoh
  • Journal Title: J.Mol.Biol. Volume: 401 Pages: 626-641
  • Peer Reviewed
• [Journal Article] Mito- cryptide-2: purification, identification, and characterization of a novel cryptide that activates neutrophils. (2009)
  • Author(s): Hidehito Mukai, Tetsuo Seki, Hiroko Nakano, Yoshinori Hokari, Toshifumi Takao, Masanori Kawanami, Hiroyuki Tsukagoshi, Hirokazu Kimura, Yoshiaki Kiso, Yasutsugu Shimonishi, Yoshisuke Nishi, Eisuke Munekata
  • Journal Title: J. Immunology Volume: 182(8) Issue: 8 Pages: 5072-5080
  • DOI: 10.4049/jimmunol.0802965
  • Peer Reviewed
• [Journal Article] Recent progress in the drug discovery of non-peptidic BACE1 inhibitors (2009)
  • Author(s): Yoshio Hamada, Yoshiaki Kiso
  • Journal Title: Expert Opinion on Drug Discovery Volume: 4(4) Issue: 4 Pages: 391-416
  • DOI: 10.1517/17460440902806377
  • 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): Yoshio Hamada, Hiroko Ohta, Naoko Miyamoto, Diganta Sarma, Takashi Hamada, Tomoya Nakanishi, Moe Yamasaki, Abdellah Yamani, Shoichi Ishiura, Yoshiaki Kiso
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 19(9) Issue: 9 Pages: 2435-2439
  • DOI: 10.1016/j.bmcl.2009.03.049
  • Peer Reviewed
• [Journal Article] Crystal structure of the histo-aspartic protease from Plasmodium falciparum. (2009)
  • Author(s): Prasenjit Bhaumik, Huogen Xiao, Charity L. Parr, Yoshiaki Kiso, Alla Gustchina, Rickey Y. Yada, Alexander Wlodawer
  • Journal Title: J. Mol. Biol. Volume: 388 Issue: 3 Pages: 520-540
  • DOI: 10.1016/j.jmb.2009.03.011
  • Peer Reviewed
• [Journal Article] efficient synthesis of isopeptide segment and application to racemization-free segment condensation. (2009)
  • Author(s): Taku Yoshiya, Hiroyuki Kawashima, YouheiSohma, Tooru Kimura, Yoshiaki Kiso: O-Acylisopeptide method
  • Journal Title: Org. Biomol. Chem. Volume: 7(14) Issue: 14 Pages: 2894-2904
  • DOI: 10.1039/b903624e
  • Peer Reviewed
• [Journal Article] Synthesis of amyloid SS peptide1-42 (E22〓) click peptide: pH-triggered in situ production of its native form. (2009)
  • Author(s): Hui Wang, Taeko Kakizawa, Atsuhiko Taniguchi, Takaaki Mizuguchi, Tooru Kimura, Yoshiaki Kiso
  • Journal Title: Bioorg. Med. Chem. Volume: 17 (14) Issue: 14 Pages: 4881-4887
  • DOI: 10.1016/j.bmc.2009.06.017
  • Peer Reviewed
• [Journal Article] Small-sized HIV-1 protease inhibitors containing allo- phenylnorstatine to explore S2' pocket. (2009)
  • Author(s): Koushi Hidaka, Tooru Kimura, Hamdy M. Abdel-Rahman, Jeffrey-Tri Nguyen, Keith F. McDaniel, William E. Kohlbrenner, Akhteru- zzaman Molla, Motoyasu Adachi, Taro Tamada, Ryota Kuroki, Noriko Katsuki, Yoshiaki Tanaka, Hikaru Matsumoto, Jun Wang, Yoshio Hayashi, Dale J. Kempf, Yoshiaki Kiso
  • Journal Title: J. Med. Chem. Volume: 52(23) Issue: 23 Pages: 7604-7617
  • DOI: 10.1021/jm9005115
  • 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): Yoshio Hamada
  • Journal Title: Bioorg.Med.Chem.Lett. 19 Pages: 2435-2439
  • Peer Reviewed
• [Journal Article] Crystal structure of the histo-aspartic protease(HAP)from Plasmodium falciparum. (2009)
  • Author(s): Prasenjit Bhaumik
  • Journal Title: J.Mol.Biol. 388 Pages: 520-540
  • Peer Reviewed
• [Journal Article] Synthesis of amyloid β peptide 1-42(E22△)click peptide : pH-triggered in situ production of its native form. (2009)
  • Author(s): Hui Wang
  • Journal Title: Bioorg.Med.Chem. 17 Pages: 4881-4887
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): Jeffrey-Tri Nguyen
  • Journal Title: Protease in Biology and Disease. Vol.8.Viral proteases and antiviral protease inhibitor therapy(Springer) Pages: 83-100
• [Presentation] Defying difficult diseases: Pro- tease inhibitors and the click peptide concept using O-acyl isopeptides. (2013)
  • Author(s): Yoshiaki Kiso
  • Organizer: AsiaTIDES Oligo- nucleotides and Peptides
  • Place of Presentation: Tokyo
  • Year and Date: 2013-02-26
• [Presentation] Harichandra D.Tagad、木曽良明:Ritter反応を用いた低分子BACEl阻害ペプチドの合成 (2013)
  • Author(s): 濱田芳男
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
• [Presentation] Defying Difficult Diseases: Protease Inhibitors and the Click Peptide Concept Using O-Acyl Isopeptides. (2013)
  • Author(s): Yoshiaki Kiso
  • Organizer: AsiaTIDES Oligonucleotides and Peptides: Research, Technology and Product Development
  • Place of Presentation: 東京
  • Invited
• [Presentation] ペプチド化学を基盤とする統合創薬科学研究：難病克服をめざして (2013)
  • Author(s): 木曽良明
  • Organizer: 長崎大学創薬シンポジウム「アカデミア創薬と探索医療」
  • Place of Presentation: 長崎
  • Invited
• [Presentation] Substrate Mimetic Inhibitors of Aspartic Proteases and Click Peptides via O-N Acyl Migration. (2012)
  • Author(s): Yoshiaki Kiso
  • Organizer: 12th Chinese International Pe- ptide Symposium
  • Place of Presentation: Shenyang, China
  • Year and Date: 2012-07-04
• [Presentation] 生物分子を基盤とした統合創薬科学。 (2012)
  • Author(s): 木曽良明
  • Organizer: 日本化学会第92春季年会「未来志向の挑戦型バイオケミカルズ」
  • Place of Presentation: 横浜
  • Year and Date: 2012-03-27
• [Presentation] Functional analysis of mito- cryptides with their monoclonal antibodies (2012)
  • Author(s): Tatsuya Hattori, Shunsuke Shirota, Takayuki Marutani, Yoshiaki Kiso, Yoshisuke Nishi, Hidehito Mukai
  • Organizer: 49th Japanese Peptide Symposium
  • Place of Presentation: Kagoshima
• [Presentation] Design and synthesis of small BACE1 inhibitor peptides. (2012)
  • Author(s): Y. Hamada, H. T. Tagad, Y. Kiso
  • Organizer: 32nd European Peptide Symposium
  • Place of Presentation: Athens, Greece
• [Presentation] Defying difficult diseases: design and synthesis of aspartic protease in- hibitors and click peptides based on the O-acyl isopeptide method. (2012)
  • Author(s): Yoshiaki Kiso
  • Organizer: 32nd European Peptide Symposium
  • Place of Presentation: Athens, Greece
• [Presentation] アロフェニルノルスタチン含有プロテアーゼ阻害剤を用いたプローブ設計。 (2012)
  • Author(s): 日高興士、木曽良明、渡海智子、赤路健一、津田裕子
  • Organizer: 日本ケミカルバイオロジー研究会第7回年会
  • Place of Presentation: 京都
• [Presentation] Substrate Mimetic Inhibitors of Aspartic Proteases and Click Peptides via O-N Acyl Migration. (2012)
  • Author(s): Yoshiaki Kiso
  • Organizer: 12th Chinese International Peptide Symposium
  • Place of Presentation: Shenyang, China
  • Invited
• [Presentation] Defying difficult diseases: design and synthesis of aspartic protease inhibitors and click peptides based on the O-acyl isopeptide method. (2012)
  • Author(s): Yoshiaki Kiso
  • Organizer: 32nd European Peptide Symposium
  • Place of Presentation: Athens, Greece
  • Invited
• [Presentation] Oxamide replacement in pseudo-symmetric HIV protease inhibitor involving multiple bridging water molecules. (2012)
  • Author(s): Koushi Hidaka
  • Organizer: 49th Japanese Peptide Symposium
  • Place of Presentation: 鹿児島市
• [Presentation] Defying Difficult Diseases: Design and Synthesis of Transition-State Mimetic Protease Inhibitors. (2011)
  • Author(s): Yoshiaki Kiso
  • Organizer: 8th AFMC International Medicinal Chemistry Symposium
  • Place of Presentation: Tokyo
  • Year and Date: 2011-12-02
• [Presentation] Defying Difficult Diseases: Aspartic Protease Inhibitors, Prodrug Forms and Click Peptides. (2011)
  • Author(s): Yoshiaki Kiso
  • Organizer: 7th General Meeting of International Proteolysis Society
  • Place of Presentation: San Diego, USA
  • Year and Date: 2011-10-19
• [Presentation] Defying difficult diseases : aspartic protease inhibitors, prodrug forms and click peptides (2011)
  • Author(s): Yoshiaki Kiso
  • Organizer: Seventh General Meeting of the International Proteolysis Society
  • Place of Presentation: San Diego, USA
  • Year and Date: 2011-10-19
• [Presentation] Design and SAR study of tripeptide BACE1 inhibitors (2011)
  • Author(s): Yoshio Hamada, Harichandra Tagad, Yo shiaki Kiso
  • Organizer: 48th Japanese Peptide Symposium
  • Place of Presentation: Sapporo
• [Presentation] BACE1阻害活性を有するペプチドの設計 (2011)
  • Author(s): 濱田芳男、濱田貴司、木曽良明
  • Organizer: 第16回日本病態プロテアーゼ学会学術集会
  • Place of Presentation: 豊中市
• [Presentation] a novel regulatory mechanism by functional peptides hidden in protein structure. (2011)
  • Author(s): Hidehito Mukai, Yoshiaki Kiso: Cryptides and their accumulative signaling
  • Organizer: 22nd American Peptide Symposium
  • Place of Presentation: San Diego
• [Presentation] タンパク質に隠された生理活性ペプチド「クリプタイド」が関わる新しい生体調節機構 (2011)
  • Author(s): 向井秀仁、保苅義則、関哲郎、深水昭吉、木曽良明
  • Organizer: 日本ケミカルバイオロジー学会第6回年会
  • Place of Presentation: 東京
• [Presentation] Cryptide : receptors and signaling mechanisms for novel neutrophil-activating peptides hidden in mitochondrial proteins (2010)
  • Author(s): H.Mukai
  • Organizer: 31st European Peptide Symposium
  • Place of Presentation: コペンハーゲン、デンマーク
  • Year and Date: 2010-09-09
• [Presentation] Use of ester-containing peptides toward understanding the functions of amyloid beta peptide and human insulin. (2010)
  • Author(s): Y.Sohma
  • Organizer: 31st European Peptide Symposium
  • Place of Presentation: コペンハーゲン、デンマーク
  • Year and Date: 2010-09-09
• [Presentation] In situ production of Alzheimer's Assmutants from water-soluble click peptide precursors. (2010)
  • Author(s): Hui Wang
  • Organizer: 11th Chinese International Peptide Symposium
  • Place of Presentation: 蘭州市、中国
  • Year and Date: 2010-07-08
• [Presentation] Mitocryptides : a novel family of neutrophil-activating peptides derived from mitochondrial proteins and their regulatory mechanisms. (2010)
  • Author(s): H.Mukai
  • Organizer: 11th Chinese International Peptide Symposium
  • Place of Presentation: 蘭州市、中国
  • Year and Date: 2010-07-07
• [Presentation] Peptidomimetic chemistry : design of protease inhibitors, prodrug forms and click peptides.12th Napes Workshop on Bioactive Peptides (2010)
  • Author(s): Y. Kiso
  • Organizer: 12th Naples Workshop on Bioactive Peptides/2nd Italy-Korea Symposium on Antimicrobial Peptides
  • Place of Presentation: ナポリ、イタリア
  • Year and Date: 2010-06-06
• [Presentation] Clarification of signaling mechanisms for mitocryptides, novel neutrophil-activating peptides hidden in mitochondrial proteins. (2010)
  • Author(s): H.Mukai
  • Organizer: 12th Naples Workshop on Bioactive Peptides/2nd Italy-Korea Symposium on Antimicrobial Peptides
  • Place of Presentation: ナポリ、イタリア
  • Year and Date: 2010-06-06
• [Presentation] Cryptides: Non-classical bioactive peptides hidden in protein structures. (2010)
  • Author(s): Hidehito Mukai, Tetsuo Seki, Yohinori Hokari, Akiyoshi Fukamizu, Yoshiaki Kiso
  • Organizer: 5th International Peptide Symposium/47th Japanese Peptide Symposium
  • Place of Presentation: Kyoto
• [Presentation] Tripeptidic BACE1 inhibitors by confor- mational structure-based design. (2010)
  • Author(s): Yoshio Hamada, Harichandra Tagad, Takashi Hamada, Tooru Kimura, Yoshiaki Kiso
  • Organizer: 5th Inter- national Peptide Symposium/ 47th Japanese Peptide Symposium
  • Place of Presentation: Kyoto
• [Presentation] ロピナビル耐性株由来の変異を導入したHIVプロテアーゼ誘導体の解析. (2010)
  • Author(s): 日高興士、安達基泰、黒木良太、濱田貴司、Sankara Rajesh、木村徹、木曽良明
  • Organizer: 第24回日本エイズ学会学術集会・総会
  • Place of Presentation: 東京
• [Presentation] アミロイドベータペプチドの機能解明を目指したO-アシルイソペプチドの利用. (2010)
  • Author(s): 相馬洋平、平山雄太、谷口敦彦、向井秀仁、木曽良明
  • Organizer: 第36回反応と合成の進歩シンポジウム-ライフサイエンスを志向した理論、反応および合成-
  • Place of Presentation: 名古屋
• [Presentation] ロピナビル耐性株由来のHIVプロテアーゼ変異体とアロフェニルノルスタチン阻害剤の相互作用解析. (2010)
  • Author(s): 日高興士、安達基泰、黒木良太、濱田貴司、Rajesh Narayanan、木村徹、木曽良明
  • 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
• [Presentation] Cryptides: receptors and signaling mechanisms for novel neutrophil-activating peptides hidden in mitochondrial proteins. (2010)
  • Author(s): H. Mukai, T. Seki, Y. Hokari, A. Fukamizu, Y. Kiso
  • Organizer: 31st European Peptides Symposium
  • Place of Presentation: Copenhagen, Denmark
• [Presentation] In situ production of Alzheimer's Aβ mutants from water-soluble click peptide precursors. (2010)
  • Author(s): Hui Wang, Taeko Kakizawa, Atsuhiko Taniguchi, Takaaki Mizuguchi, Youhei Sohma, Hidehito Mukai, Tooru Kimura, Yoshiaki Kiso
  • Organizer: 11th Chinese International Peptide Symposium
  • Place of Presentation: Lanzhou, China
• [Presentation] Peptidomimetic chemistry: design of protease inhibitors, prodrug forms and click peptides. (2010)
  • Author(s): Y. Kiso
  • Organizer: 12th Napes Workshop on Bioactive Peptides / 2nd Italy-Korea Symposium on Antimicrobial Peptides
  • Place of Presentation: Napoli, Italy
• [Presentation] アミロイドβペプチドおよびインスリンの機能解明を目指したエステル含有ペプチドの利用. (2010)
  • Author(s): 相馬洋平、谷口敦彦、向井秀仁、StephenKent、木曽良明
  • Organizer: 日本ケミカルバイオロジー学会第5回年会
  • Place of Presentation: 横浜
• [Presentation] "クリックペプチド":水溶性プレカーサーによるアルツハイマー病関連Aβ変異体の産生. (2010)
  • Author(s): 王惠、柿澤多惠子、谷口敦彦、水口貴章、相馬洋平、向井秀仁、木村徹、木曽良明
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] 新規抗マラリア治療薬を目指したプラスメプシン阻害剤研究:酵素ポケット外での新たな相互作用. (2010)
  • Author(s): 三浦拓也、日高興士、上村剛史、柏本啓介、Ernesto Freire、木村徹、木曽良明
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] O-Acyl isopeptide method : an efficient preparation of amyloidogenic peptide by use of racemization-free segment condensation. (2010)
  • Author(s): A.Higa
  • Organizer: 31st European Peptide Symposium
  • Place of Presentation: コペンハーゲン、デンマーク
• [Presentation] S-Acyl isopeptide method : preparation of thioester-containing isopeptide by Fmoc-based SPPS with Alov group. (2010)
  • Author(s): T.Yoshiya
  • Organizer: 31st European Peptide Symposium
  • Place of Presentation: コペンハーゲン、デンマーク
• [Presentation] "Click peptide" based on"O-acyl isopeptide method" : in situ production of monomer amyloid β peptide from water-soluble precursor analogs. (2009)
  • Author(s): Atsuhiko Taniguchi
  • Organizer: 21st American Peptide Symposium
  • Place of Presentation: Bloomington, USA
  • Year and Date: 2009-06-09
• [Presentation] Characterization of signaling mechanisms for mitocryptides, novel neutorphil-activating cryptides isolated from porcine heart. (2009)
  • Author(s): Tetsuo Seki, Yoshinori Hokari, Akiyoshi Fukamizu, Yoshiaki Kiso, Hidehito Mukai
  • Organizer: The 32nd Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Yokohama
• [Presentation] 架橋水および水和を利用するHIVプロテアーゼ阻害剤研究. (2009)
  • Author(s): 日高興士、Jeffrey-TriNguyen、濱田貴司、安達基泰、黒木良太、木村徹、木曽良明
  • Organizer: 第23回日本エイズ学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] プラスメプシンを標的とした新規抗マラリア治療薬の開発:酵素ポケット外へのアミノ置換基の伸長. (2009)
  • Author(s): 三浦拓也、日高興士、上村剛史、柏本啓介、木村徹、木曽良明、Ernesto Freire
  • Organizer: 第28回メディシナルケミストリーシンポジウム
  • Place of Presentation: 東京
• [Presentation] Defying difficult diseases:Peptidomimetic protease inhibitors, prodrug forms and click peptides. (2009)
  • Author(s): Yoshiaki Kiso
  • Organizer: 3rd Asia-Pacific International Peptide Symposium/ 13th Korean Peptide & Protein Symposium
  • Place of Presentation: Jeju Island, Korea
• [Presentation] Significance of wild-type APP sequence in developing the BACE1 inhibitors. (2009)
  • Author(s): Yoshio Hamada, Daisuke Shuto, Ping Liu, Takashi Hamada, Koushi Hidaka, Tooru Kimura, Yoshiaki Kiso
  • Organizer: 46th Japanese Peptide Symposium
  • Place of Presentation: Kitakyushu, Japan
• [Presentation] HIV protease inhibitor design to employ water molecules. (2009)
  • Author(s): K. Hidaka, T. Hamada, M. Adachi, R. Kuroki, T. Kimura, Y. Kiso
  • Organizer: Sixth General Meeting of the International Proteo- lysis Society
  • Place of Presentation: Gold Coast, Australia
• [Presentation] 非ペプチド型BACE1阻害剤の設計と構造活性相関. (2009)
  • Author(s): 濱田芳男、大田博子、Diganta Sarma、中西智哉、Abdellah Yamani、山口亮司、日高興士、木村徹、石浦章一、木曽良明
  • Organizer: 第14回日本病態プロテアーゼ学会
  • Place of Presentation: 吹田
• [Presentation] In situ production of Alzheimer's disease-related amyloid s peptide from water- soluble precursor analogs. (2009)
  • Author(s): Atsuhiko Taniguchi, Youhei Sohma, Mariusz Skwarczynski, Yuta Hirayama, Takuma Okada, Keisuke Ikeda, Halan Prakash, Hidehito Mukai, Tooru Kimura, Yoshio Hayashi, Shun Hirota, Katsumi Matsuzaki, Yoshiaki Kiso: Click peptide
  • Organizer: 238th American Chemical Society National Meeting
  • Place of Presentation: Washington DC, USA
• [Presentation] discovery of functional cryptic peptides hidden in protein structures and identification of their signaling mechanisms (2009)
  • Author(s): H. Mukai, T. Seki, E. Munekata, Y. Kiso: Cryptides
  • Organizer: 21st American Peptide Symposium
  • Place of Presentation: Bloomington, USA
• [Book] Handbook of Proteolytic Enzymes3rd Edition. (2013)
  • Author(s): Jeffrey-Tri Nguyen, Yoshiaki Kiso
  • Publisher: Human T-cell leukemia virus type I (HTLV-I) retropepsin.
• [Book] Handbook of Proteolytic Enzymes 3rd Edition (2013)
  • Author(s): Jeffrey-Tri Nguyen
  • Publisher: Elsevier
• [Book] ペプチド医薬の最前線 (2013)
  • Author(s): 木曽良明
  • Total Pages: 240
  • Publisher: シーエムシー出版
• [Book] 遺伝子医学MOOK21号最新ペプチド合成技術とその創薬研究への応用(木曽良明編集)O-アシルイソペプチドの合成. (2012)
  • Author(s): 相馬洋平・木曽良明
  • Publisher: メディカル・ドゥ
• [Book] アルツハイマー病治療薬をめざしたBACE1阻害剤の設計と合成.遺伝子医学MOOK21号最新ペプチド合成技術とその創薬研究への応用(木曽良明編集) (2012)
  • Author(s): 濱田芳男・木曽良明
  • Publisher: メディカル・ドゥ
• [Book] クリプタイド:タンパク質に隠された新しい生理活性ペプチド-その発見と存在意義および効率的スクリーニング。遺伝子医学MOOK21号最新ペプチド合成技術とその創薬研究への応用(木曽良明編集) (2012)
  • Author(s): 向井秀仁・木曽良明
  • Publisher: メディカル・ドゥ
• [Book] 遺伝子医学MOOK 21号最新ペプチド合成技術とその創薬研究への応用 (2012)
  • Author(s): 木曽良明
  • Total Pages: 316
  • Publisher: メディカル・ドゥ
• [Book] 最新ペプチド合成技術とその創薬研究への応用 (2012)
  • Author(s): 濱田芳男・木曽良明
  • Publisher: メディカル・ドゥ
• [Book] Amino Acids Peptides & Proteins in Organic Chemistry, Vol. 4 (ed. By Andrew Hughes) Wiley-VCH (2011)
  • Author(s): Zyta Ziora, Mariusz Skwarczynski, Yoshiaki Kiso
  • Publisher: Medicinal chemistry of α-hydroxy-SS- amino acids.
• [Book] Methods and Principles in Medicinal Chemistry, Volume 45 (Aspartic Acid Proteases as Therapeutic Targets) (2010)
  • Author(s): Adam J. Ruben, Yoshiaki Kiso
  • Publisher: The plasmepsin family as antimalarial drugtargets.
• [Book] Aspartic Acid Proteases as Therapeutic Targets. (2010)
  • Author(s): Adam J.Ruben
  • Publisher: Wiley-VCH Verlag GmbH & Co
• [Book] Wiley Encyclopedia of Chemical Biology, Volume 1 (Tadhg P. Begley, Chief Advisor) (2009)
  • Author(s): Yoshiaki Kiso, Atsuhiko Taniguchi, Youhei Sohma
  • Publisher: Click Peptides: Design and Applica- tions.
• [Book] Viral Proteases and Antiviral Protease Inhibitor Therapy: Proteases in Biology and Disease (Uwe Lendeckel & Nigel M. Hooper, eds.) (2009)
  • Author(s): Jeffrey-Tri Nguyen, Yoshiaki Kiso
  • Publisher: Rational Drug Design of HTLV-1 Protease Inhibitors.