Researcher Database


HIGUCHI Tsunehiko

FacultyGraduate School of Pharmaceutical Sciences Department of Bioorganic-inorganic Chemistry
Last Updated :2020/07/02

Researcher Profile and Settings


  • Ph D, The University of Tokyo

Association Memberships

  • The American Chemical Society
  • Society for Free Radical Research JAPAN
  • The Chemical Society of Japan
  • The Pharmaceutical Society of Japan

Research Activities

Research Areas

  • Life sciences, Bioorganic chemistry, bioorganic chemistry
  • Nanotechnology/Materials, Structural/physical organic chemistry, bioorganic chemistry
  • Nanotechnology/Materials, Inorganic and coordination chemistry, bioinorganic chemistry
  • Life sciences, Pharmaceuticals - chemistry and drug development
  • Life sciences, Pharmaceuticals - chemistry and drug development

Published Papers

  • Methylene chain ruler for evaluating the regioselectivity of a substrate-recognising oxidation catalyst., Teramae S, Kito A, Shingaki T, Hamaguchi Y, Yano Y, Nakayama T, Kobayashi Y, Kato N, Umezawa N, Hisamatsu Y, Nagano T, Higuchi T, Chemical communications (Cambridge, England), 55, (58) 8378 - 8381, 07 , Refereed
  • Stable Iron Porphyrin Intramolecularly Coordinated by Alcoholate Anion: Synthesis and Evaluation of Axial Ligand Effect of Alcoholate on Spectroscopy and Catalytic Activity., Shirakawa Y, Yano Y, Niwa Y, Inabe K, Umezawa N, Kato N, Hisamatsu Y, Higuchi T, Inorganic chemistry, 58, (7) 4268 - 4274, 04 , Refereed
  • Effect of the o-Acetamido Group on pH-Dependent Light Emission of a 3-Hydroxyphenyl-Substituted Dioxetane Luminophore., Hisamatsu Y, Fukiage T, Honma K, Balia AG, Umezawa N, Kato N, Higuchi T, Organic letters, 21, (5) 1258 - 1262, 03 , Refereed
  • Repulsive/attractive interaction among compact DNA molecules as judged through laser trapping: difference between linear- and branched-chain polyamines, Kashiwagi Yusuke, Nishio Takashi, Ichikawa Masatoshi, Shew Chwen-Yang, Umezawa Naoki, Higuchi Tsunehiko, Sadakane Koichiro, Yoshikawa Yuko, Yoshikawa Kenichi, COLLOID AND POLYMER SCIENCE, 297, (3) 397 - 407, 03 , Refereed
  • Distinct modulation of group I ribozyme activity among stereoisomers of a synthetic pentamine with structural constraints., Gulshan MA, Tsuji K, Matsumura S, Higuchi T, Umezawa N, Ikawa Y, Biochemical and biophysical research communications, 504, (4) 698 - 703, 10 , Refereed
  • Hydrogen sulfide bypasses the rate-limiting oxygen activation of heme oxygenase, oshitaka Matsui, Ryota Sugiyama, Kenta Sakanashi, Yoko Tamura, Masaki Iida, Yukari Nambu, Tsunehiko Higuchi, Makoto Suematsu, Masao Ikeda-Saito, Journal of Biological Chemistry, 293, (43) 16931 - 16939, 10 , Refereed
  • Branched-Chain Polyamine Found in Hyperthermophiles Induces Unique Temperature-Dependent Structural Changes in Genome-Size DNA, Takashi Nishio, Yuko Yoshikawa, Wakao Fukuda, Naoki Umezawa, Tsunehiko Higuchi, Shinsuke Fujiwara, Tadayuki Imanaka, Kenichi Yoshikawa, ChemPhysChem, 19, (18) 2299 - 2304, 09 , Refereed
  • Comparative study of polyethylene polyamines as activator molecules for a structurally unstable group I ribozyme., Gulshan MA, Matsumura S, Higuchi T, Umezawa N, Ikawa Y, Bioscience, biotechnology, and biochemistry, 82, (8) 1404 - 1407, 08 , Refereed
  • A small-molecule inhibitor of SOD1-Derlin-1 interaction ameliorates pathology in an ALS mouse model, Naomi Tsuburaya, Kengo Homma, Tsunehiko Higuchi, Andrii Balia, Hiroyuki Yamakoshi, Norio Shibata, Seiichi Nakamura, Hidehiko Nakagawa, Shin-ichi Ikeda, Naoki Umezawa, Nobuki Kato, Satoshi Yokoshima, Masatoshi Shibuya, Manabu Shimonishi, Hirotatsu Kojima, Takayoshi Okabe, Tetsuo Nagano, Isao Naguro, Keiko Imamura, Haruhisa Inoue, Takao Fujisawa, Hidenori Ichijo, Nature Communications, 9, (1) , 07 , Refereed
  • Biogenic triamine and tetraamine activate core catalytic ability of Tetrahymena group I ribozyme in the absence of its large activator module, Mst Ara Gulshan, Md Motiar Rahman, Shigeyoshi Matsumura, Tsunehiko Higuchi, Naoki Umezawa, Yoshiya Ikawa, Biochemical and Biophysical Research Communications, 496, (2) 594 - 600, 02 , Refereed
  • Nitrous Oxide Reduction-Coupled Alkene-Alkene Coupling Catalysed by Metalloporphyrin, Shunsuke Saito, Hiro Ohtake, Naoki Umezawa, Yuko Kobayashi, Nobuki Kato, Masaaki Hirobe, Tsunehiko Higuchi, Chemical Communications, 49, (79) 8979 - 8981, 10 , Refereed
  • Manganese Salen Complexes with Acid-Base Catalytic Auxiliary: Functional Mimetics of Catalase, Yukinobu Noritake, Naoki Umezawa, Nobuki Kato, Tsunehiko Higuchi, Inorganic Chemistry, 52, (7) 3653 - 3662, 04 , Refereed
  • Synthesis of the Carbon Framework of Scholarisine A by Intramolecular Oxidative Coupling, Tsugunori Watanabe, Nobuki Kato, Naoki Umezawa, Tsunehiko Higuchi, Chemistry - A European Journal, 19, (13) 4255 - 4261, 03 , Refereed
  • Effective Chiral Discrimination of Tetravalent Polyamines on Single-DNA Compaction, Yuko Yoshikawa, Naoki Umezawa, Yuki Imamura, Toshio Kanbe, Nobuki Kato, Kenichi Yoshikawa, Tadayuki Imanaka, Tsunehiko Higuchi, Angewandte Chemie International Edition, 52, (13) 3712 - 3716, 03 , Refereed
  • Effect of Helical Conformation and Side Chain Structure on gamma-Secretase Inhibition by beta-Peptide Foldamers: Insight into Substrate Recognition, Yuki Imamura, Naoki Umezawa, Satoko Osawa, Naoaki Shimada, Takuya Higo, Satoshi Yokoshima, Tohru Fukuyama, Takeshi Iwatsubo, Nobuki Kato, Taisuke Tomita, Tsunehiko Higuchi, JOURNAL OF MEDICINAL CHEMISTRY, 56, (4) 1443 - 1454, 02 , Refereed, Substrate-selective inhibition or modulation of the activity of gamma-secretase, which is responsible for the generation of amyloid-beta peptides, might be an effective strategy for prevention and treatment of Alzheimer's disease. We have shown that helical beta-peptide foldamers are potent and specific inhibitors of gamma-secretase. Here we report identification of target site of the foldamers by using a photoaffinity probe. The photoprobe directly and specifically labeled the N-terminal fragment of presenilin 1, in which the initial substrate docking site is predicted to be located. We also optimized the foldamer structure by preparing a variety of derivatives and obtained two highly potent foldamers by incorporation of a hydrophilic and neutral functional group into the parent structure. The class of side chain functional group and the position of incorporation were both important for gamma-secretase-inhibitory activity. The substrate selectivity of the inhibitory activity was also quite sensitive to the class of side chain group incorporated.
  • Inhibition of gamma-Secretase Activity by Helical beta-Peptide Foldamers, Yuki Imamura, Naoto Watanabe, Naoki Umezawa, Takeshi Iwatsubo, Nobuki Kato, Taisuke Tomita, Tsunehiko Higuchi, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 131, (21) 7353 - 7359, 06 , Refereed, Alzheimer's disease (AD) is a neurodegenerative disorder pathologically characterized by extensive extracellular deposition of amyloid-beta (A beta) peptides as senile plaques, and inhibition of "amyloidogenic" amyloid precursor protein (APP) processing by gamma-secretase is an important strategy for prevention and treatment of AD. Here we show that beta-peptide foldamers designed to adopt a 12-helical conformation in solution are potent and specific inhibitors of gamma-secretase. Subtle modifications that disrupt helicity substantially reduce inhibitory potency, suggesting that helical conformation is critical for effective inhibition. These beta-peptides competed with helical peptide-type inhibitor, suggesting that they interact with the substrate binding site of gamma-secretase. The beta-peptide with inhibitory activity at nanomolar concentration should be a useful lead compound for development of gamma-secretase-specific inhibitors and molecular tools to explore substrate recognition by intramembrane proteases.
  • [Fluorescent detection of protein kinase activity: methodology to visualize "phosphate"]., Umezawa N, Higuchi T, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme, 52, (13 Suppl) 1601 - 1607, 10 , Refereed
  • Evaluation of 3-Substituted Arginine Analogs as Selective Inhibitors of Human Nitric Oxide Synthase Isozymes, Ijuin, Ryosuke, Umezawa, Naoki, Nagai, Shin-ichi, Higuchi,Tsunehiko, Bioorg. Med. Chem. Lett., 15, (11) 2881 - 2885, 06 , Refereed
  • Intramolecular fluorescence resonance energy transfer system with coumarin donor included in beta-cyclodextrin, H Takakusa, K Kikuchi, Y Urano, T Higuchi, T Nagano, ANALYTICAL CHEMISTRY, 73, (5) 939 - 942, 03 , In aqueous solutions, the fluorescence of the intramolecular fluorescence resonance; energy-transfer (FRET) system 1 mas strongly quenched, because of close contact between the donor and acceptor moieties, FRET occurred, and the acceptor fluorescence was increased, by adding beta -cyclodextrin (beta -CD) to aqueous solutions of 1. Spectral analysis supported the idea that the FRET enhancement was due to the formation of an inclusion complex of the coumarin moiety in beta -CD, resulting in separation of the fluorophores, On the basis of this result, we propose that covalent binding of coumarin to beta -CD will provide a FRET cassette molecule. So, compound 2 bearing beta -CD covalently was designed and synthesized. Fluorescence intensity of 2 was enhanced markedly compared to the intensity of 3. Applying this FRET system, various FRET probes that will be useful for ratio imaging and also the high-throughput screening will be provided.
  • Rational Design of Fluorescein-Based Fluorescence Probes. Mechanism-Based Design of a Maximum Fluorescence Probe for Singlet Oxygen, Tanaka, Kumi, Miura, Tetsuo, Umezawa, Naoki, Urano, Yasuteru, Kikuchi, Kazuya, Higuchi, Tsunehiko, Nagano, Tetsuo, J. Am. Chem. Soc., 123, (11) 2530 - 2536
  • Selective Inhibition of Human Inducible Nitric Oxide Synthase by S-alkyl-L-isothiocitrulline-containing Dipeptides, Park, Jung-Min, Higuchi, Tsunehiko, Kikuchi, Kazuya, Urano, Yasuteru, Hori, Hiroyuki, Nishino, Takeshi, Aoki, Junken, Inoue, Keizo, Nagano, Tetsuo, Br. J. Pharamacol., 132, (8) 1876 - 1882
  • Synthesis of 5, 10, 15, 20-Tetrakis(4-┣DBtert(/)-┫DB-buty1-2, 6-dicarboxyphenyl)porphyrin : A Versatile Bis-Fased Porphyrin Synthon hof D, Nakagawa, Hiroshi, Nagano, Tetsuo, Higuchi, Tsunehiko, Org. Lett., 3, (12) 1805 - 1807
  • Design and synthesis of intramolecular resonance-energy transfer probes for use in ratiometric measurements in aqueous solution, Kawanishi, Yasutomo, Kikuchi, Kazuya, Takakusa,Hideo, Mizukami, Shin, Urano, Yasuteru, Higuchi, Tsunehiko, Nagano, Tetsuo, Angew. Chem. Int. Ed., 39, (19) 3438 - 3440
  • Fluorescence switching by O-dearylation of 7-aryloxycoumarins. Development of novel fluorescence probes to detect reactive oxygen species with high selectivity, Setsukinai, Ken-ichi, Urano, Yasuteru, Kikuchi, Kazuya, Higuchi, Tsunehiko, Nagano, Tetsuo, Perkin 2, (12) 2453 - 2457
  • Novel Zinc Fluorescent Probes Excitable with Visible Light for Biological Applications, Hirano T, Kikuchi K, Urano Y, Higuchi T, Nagano T, Angew. Chem. Int. Ed., 39, (6) 1052 - 1054
  • First Synthetic NO-heme-thiolate Complex Relevant to Nitric Oxide Synthase and Cytochrome P450nor, Suzuki, Noriyuki, Higuchi, Tsunehiko, Urano, Yasuteru, Kikuchi, Kazuya, Uchida, Takeshi, Mukai, Masahiro, Kitagawa, Teizo, Nagano, Tetsuo, J. Am. Chem. Soc., 122, (48) 12059 - 12060
  • Fluorescent Indicators for Imaging Nitric Oxide Production, Kojima, Hirotatsu, Urano, Yasuteru, Kikuchi, Kazuya, Higuchi, Tsunehiko, Hirata, Yasunobu, Nagano, Tetsuo, Angew. Chem. Int. Ed., 38, (21) 3209 - 3212
  • Dipeptides Containing L-Arginine Analogs : New Isozyme-Selective Inhibitors of Nitric Oxide Synthase, Kobayashi, Nobutaka, Higuchi, Tsunehiko, Urano, Yasuteru, Kikuchi, Kazuya, Hirobe, Masaaki, Nagano, Tetsuo, Biol. Pharm. Bull., 22, (9)
  • Novel Iron Porphyrin-alkanethiolate Complex with Intramolecular NH…S Hydrogen Bond : Synthesis, Spectroscopy and Reactivity, Suzuki, Noriyuki, Higuchi, Tsunehiko, Urano, Yasuteru, Kikuchi, Kazuya, Uekusa, Hidehiro, Ohashi, Yuji, Uchida, Takeshi, Kitagawa, Teizo, Nagano, Tetsuo, J. Am. Chem. Soc., 121, (49) 11571 - 11572
  • Improved nitric oxide detection using 2,3-diaminonaphthalene and its application to the evaluation of novel nitric oxide synthase inhibitors, Nakatsubo, Naoki, Kojima, Hirotatsu, Sakurai, Kuniko, Kikuchi, Kazuya, Nagoshi, Hiroshi, Hirata, Yasunobu, Akaike, Takaaki, Maeda, Hiroshi, Urano, Yasuteru, Higuchi, Tsunehiko, Nagano, Tetsuo, Chem. Pharm. Bull., 21, (12) 1247 - 1250
  • 酵素機能に対するポルフィリン配位構造の必然性, 樋口恒彦, 化学と生物, 36, (2)
  • Pronounced Axial Thiolate Ligand Effect on the Reactivity of High-Valent Oxo-Iron Porphyrin Intermediate, Urano, Yasuteru, Higuchi, Tsunehiko, Hirobe, Masaaki, Nagano, Tetsuo, J. Am. Chem. Soc., 119, (49)
  • Regio-and Stereo-selective Oxidation of Steroids Using 2,6-Dichloropyridine N-Oxide Catalysed by Ruthenium Porphyrins, Shigeaki, Tomoteru, Miura, Keiko, Higuchi, Tsunehiko, Hirobe, Masaaki, Nagano, Tetsuo, Chem. Commun., (9)
  • シトクロムP450における反応性とチオレート軸配位子との関わり:モデルからのアプローチ, 樋口恒彦, ポルフィリン, 6, (2)
  • 生体類似型酸化反応系[銅-アスコルビン酸-酸素]系-フェノール、アニソール類の選択的酸化とその反応機構および生理活性物質創製への応用, Aihara, Kazuhiro, Urano, Yasuteru, Higuchi, Tsunehiko, Hirobe, Masaaki, 有機合成化学協会誌, 55, (3) 196 - 206
  • Four Recent Studies in Cytochrome P450 Modelings : A Stable Iron Porphyrin Coordinated by a Thiolate Ligand ; A Robust Ruthenium Porphyrin-Pyridine N-Oxide derivatives System ; Polypeptide-bound Iron Porphyrin ; Application to Drug Metabolism Studies, Higuchi, Tsunehiko, Hirobe, Masaaki, J. Mol. Cat. A Chemical, 113
  • Substrate-dependentChanges of Oxidative Ο-Dealkylation Mechanism of Several Chemical and Biological Oxidizing System, Urano, Yasuteru, Higuchi, Tsunehiko, Hirobe, Masaaki, J. Chem.l Soc. Perkin 2, (6) 1169 - 1173
  • Application of chemical P-450 model systems to studies on drug metabolism. Part X. Novel hydroxylactonization of γ,δ- and β,γ-unsaturated carboxylic acids with an iron porphyrin-iodosylbenzenesystem, Komuro, Masakatsu, Higuchi, Tsunehiko, Hirobe, Masaaki, J. Chem. Soc. Perkin 1, (18) 2309 - 2313
  • Application of Chemical Cytochrome P-450 Model Systems to Studies on Drug Metabolism-VIII. Novel Metabolism of Carboxylic Acids via Oxidative Decarboxylation, Komuro, Masakatsu, Higuchi, Tsunehiko, Hirobe, Masaaki, Bioorg. Med. Chem., 3, (1) 55 - 65
  • シンクロムP450のO-O結合開裂機構をめぐる論争, 樋口恒彦, ファルマシア, 31
  • 含窒素芳香族複素環N-オキシドールテニウムポルフィリン触媒系による多様な高効率酸化反応, 樋口恒彦, 有機合成化学協会誌, 53, (7) 633 - 644
  • Mechanistic Studies of Selective Catechol Formation from o-Methoxyphenols Using A Copper(II)-Ascorbic Acid-Dioxygen System, Aihara, Kazuhiro, Urano, Yasuteru, Higuchi, Tsunehiko, Hirobe, Masaaki, J. Chem.l Soc. Perkin 2, (11) 2165 - 2170
  • Highly Efficient Oxidation of Alkanes and Alkyl Alcohols with Heteroaromatic N-Oxides Catalyzed by Ruthenium Porphyrins, Ohtake, Hiro, Higuchi, Tsunehiko, Hirobe, Masaaki, J. Am. Chem. Soc., 114, 10660 - 11661
  • Oxidative Decarboxylation of Carboxylic Acids by Iron Porphyrin-Iodosylbenzene System, Komuro, Masakatsu, Higuchi, Tsunehiko, Hirobe, Masaaki, Tetrahedron Lett., 33, (34)
  • Comformation and Stereoselective Reduction of Hapten Side Chains in the Antibody Combining Site., Kim, Jae Il, Nagano, Tetsuo, Higuchi, Tsunehiko, Hirobe, Masaaki, Shimada, Ichio, Arata, Yoji, J. Am. Chem. Soc., 113, (24) 9392 - 9394
  • 3-Hydroxycoumarins: first direct preparation from coumarins using a copper(2+)-ascorbic acid-oxygen system, and their potent bioactivities, Aihara, Kazuhiro, Higuchi, Tsunehiko, Hirobe, Masaaki, Biochem Biophys Res Commun., 168, (1) 169 - 175
  • Application of chemical P-450model systems to study drug metabolism. III. Metabolism of 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine, Nagatsu, Yoshio, Higuchi, Tsunehiko, Hirobe, Masaaki, Chem. Pharm. Bull., 38, (2) 400 - 403
  • Synthesis of a highly stable iron porphyrin coordinated by alkylthiolate anion as a model for cytochrome P-450 and its catalytic activity in oxygen-oxygen bond cleavage, Higuchi, Tsunehiko, Uzu, Shinobu, Hirobe, Masaaki, J. Am. Chem. Soc., 112, (19) 7051 - 7053
  • Increasing 5-Lipoxygenase Inhibitory Activities by Oxidative Conversion of o-Methoxyphenols to Catechols Using Cu, Aihara, Kazuhiro, Higuchi, Tsunehiko, Hirobe, Masaaki, Chem. Pharm. Bull., 38, (3)
  • Highly efficient epoxidation of olefins with pyridine N-oxides catalyzed by ruthenium porphyrins, Higuchi, Tsunehiko, Ohtake, Hiro, Hirobe, Masaaki, Tetrahedron Lett., 30, (47) 6545 - 6547
  • Identification and Quantification of p-Hydroxyethylamphetamine as a Novel Metabolite of Ethylamphetamine in Rat by Gas Chromato-graphy-Mass Spectrometry, Makino, Yukiko, Higuchi, Tsunehiko, Ohta, Shigeru, Hirobe, Masaaki, Forensic Science International, 41
  • Facile Preparation of Unstable Metabolic Intermediates : Epoxide(s) of Pyrazolo[1,5-a]pyridine Derivatives by Cytochrome P-450 Chemical Model, Nagatsu, Yoshio, Higuchi, Tsunehiko, Hirobe, Masaaki, Chem. Pharm. Bull., 37
  • Versatile chiral synthons for vic-amino alcohols. Facile synthesis of (2S,3R)-3-hydroxyglutamic acid and (+)-statine, Kunieda, Takehisa, Ishizuka, Tadao, Higuchi, Tsunehiko, Hirobe, Masaaki, J. Org. Chem., 53, (14) 3381 - 3383
  • Highly Efficient Oxazolone-derived Reagents for β-Lactam Formation from β-Amino Acids, Kunieda, Takehisa, Nagamatsu, Tomohisa, Higuchi, Tsunehiko, Hirobe, Masaaki, Tetrahedron Lett., 29, (18)
  • Oxygen-copper(2+)-ascorbic acid: a novel oxidation system for the highly selective O-dealkylation of 2-alkoxyphenols, Aihara, Kazuhiro, Higuchi, Tsunehiko, Hirobe, Masaaki, Chem. Pharm. Bull., 36
  • 3-Acyl-2-Oxazolone-zirconium Complex As Excellent Reagents for Highly Regioselective Acylation of Polyalcohols, Kunieda, Takehisa, Mori, Takashi, Higuchi, Tsunehiko, Hirobe, Masaaki, Tetrahedron Lett., 26, (16)
  • 3-Alkoxycarbonyl-2-oxazolones and Their Homopolymers as Highly Preservable Amino-protecting Reagents. tert-Butoxycarbonylation of Amino Groups., Kunieda, Takehisa, Higuchi, Tsunehiko, Abe, Yoshihiro, Hirobe, Masaaki, Chem. Pharm. Bull., 32, (6) 2174 - 2181


  • Photo-regulation of peptide function, 梅澤 直樹, 樋口 恒彦, 生体の科学, 66, (2) 102 - 107,   2015 03
  • Synthesis of the Carbon Framework of Scholarisine A by Intramolecular Oxidative Coupling, Kato Nobuki, Watanabe Tsugunori, Umezawa Naoki, Higuchi Tsunehiko, Symposium on the Chemistry of Natural Products, symposium papers, 56,   2014 , <p>Scholarisine A (1), isolated from the leaves of Alstonia scholaris, is a monoterpene indole alkaloid which possesses an unprecedented cage-like structure. The unique and complex architecture of scholarisine A (1) has fascinated synthetic chemists. </p><p>We planned to construct the 10-oxa-tricyclo[<sup>3,8</sup>]undecan-9-one structure fused with indolenine, the core skeleton of 1, by linking C7 and C16 via intramolecular oxidative coupling in the late stage. Although several examples of intramolecular oxidative coupling between activated a-carbonyl carbon and indole C3 have been reported, there is no case involving a non-activated lactone. In order to obtain the information for the synthesis of scholarisine A (1), we examined to synthesize 4which is a model compund of 1.</p><p>Coupling between bromide 8 and aldehyde 9, and acetylation of the resulting alcohol gave diene 21. Ring closing metathesis using Grubbs catalyst second generation to construct the 8-membered ring proceeded efficiently and the product 22 was further converted to lactone 5 in several steps. In the ring closing metathesis step, when the compound with no acetyl group was used as the substrate, only the undesired dimer was obtained, and protecting the hydroxyl group was crucial. Finally, intramolecular oxidative coupling of dianion generated from lactone 5 using NIS as the oxidant gave the target compound 4with moderate yield.</p><p>Thus, intramolecular oxidative coupling reaction is an effective tool for the construction of complex structures, and a non-activated lactone can also be employed as a substrate. Based on the chemistry described herein, further studies directed toward total synthesis of scholarisine A are under way.</p>
  • Inevitable Cytochrome P450 Coordination Structure for Enzyme Function: Chemical Model Approach to Elucidation of the Axial Ligand Effect, Tsunehiko Higuchi, JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN, 67, (2) 134 - 142,   2009 02 , A distinctive structural feature of P450 is the unusual thiolate coordination to heme. We have succeeded in the preparation of the first synthetic thiolato-iron porphyrin (SR complex) that retains its structure during catalytic oxidation. Experiments using SR complex have revealed that the thiolate ligand greatly accelerates the rate of the O-O bond cleavage and its heterolysis even in highly hydrophobic media. Prostaglandin H-2 (PGH(2)) is catalytically isomerized to prostacyclin or thromboxane A(2) by cytochrome P450s. We investigated the isomerization mechanism of PGH(2) using SR complex, which is a model of P450 having heme-thiolate structure. Isomerization of endoperoxide proceeded very rapidly with SR, whereas imidazole or chloride-ligated heme had slight or no catalytic activity. The results of kinetic isotope effects in the oxidative demethylation of p-dimethoxybenzene unambiguously showed that the formed active intermediates of heme-thiolates are different from those of hemes coordinated by imidazole or chloride. Novel iron porphyrin-alkanethiolate complexes were prepared in order to examine the influence of the NH-S hydrogen bond on catalytic oxidation. The complexes were characterized by IR, EPR, resonance Raman spectroscopies and crystal structure analysis and their redox potentials were measured. Our work also reports some spectroscopic and electrochemical properties of the first synthetic NO-heme-thiolate complex, prepared by treatment of SR with NO, relevant to NO synthase.
  • Anomalous Enhancing Effect of NH•••S Hydrogen Bonding on the Catalytic Activity of Heme Coordinated by Thiolate, Suzuki Hiroshi, Yamane Takehiro, Umezawa Naoki, Kato Nobuki, Higuchi Tsunehiko, Proceedings of the Symposium on Progress in Organic Reactions and Syntheses, 35, (0) 27 - 27,   2009 , Cytochrome P450 and NO synthase have strong oxidizing ability and unusual structure, in that their heme irons have thiolate coordination. Recently, the presence of an NH···S hydrogen bond in the active site of P450 and NOS has been confirmed. We have succeeded in the synthesis of the first synthetic heme thiolate (SR complex) which retains thiolate coordination during catalytic oxidation, and also have prepared heme thiolate having NH···S hydrogen bond (SR-HB complex). We have found that catalytic oxidizing activity of SR-HB is considerably higher than that of SR complex. We have also found that redox potential (Fe(III)/Fe(IV)) of SR-HB is lower than that of SR, contrary to expectation. This finding would involve function of NH···S hydrogen bond as a positive modulator of P450 catalysis.
  • Synthesis of a Ruthenium Porphyrin Having Substrate-Recognition Sites and Its Catalytic Regio-Selective Oxidation of Guests, Kito Akane, Shingaki Tomoteru, Nagano Tetsuo, Umezawa Naoki, Higuchi Tsunehiko, Proceedings of the Symposium on Progress in Organic Reactions and Syntheses, 30, (0) 184 - 185,   2004 , The selectivity on the oxidation by cytochrome P450 is probably due to appropriate arrangement of a substrate near the active intermediate of an enzyme by molecular recognition. We have found that ruthenium (Ru) porphyrin&ndash;pyridine <i>N</i>-oxide system is an exceptionally potent and efficient oxidizing one for unactivated alkanes, and so on. Ru porphyrin with substrate-recognition sites (<b>1</b>) is expected to be superior to simple Ru porphyrin in both selectivity and efficiency. <sup>1</sup>H-NMR study showed that substrate <b>2</b> (tetradecane form), <b>3</b> (dodecane form) well makes 1:1 complex with <b>1</b> by multiple hydrogen bonding. By the addition of 2,6-dichloropyridine <i>N</i>-oxide, <b>2</b>, <b>3</b> was oxidized with high regio-selectivity. On the other hand, Ru porphyrin without recognition sites gave no product. These results provide evidence that substrate recognition by a catalyst is advantageous for high regio-selectivity and high reactivity.
  • Unique Oxidation Reaction of Amides with Pyridine-N-oxide Catalyzed by Ruthenium Porphyrin – Direct Oxidative Conversion of N-Acyl-L-prolines to N-Acyl-L-glutamates, Ito Rina, Umezawa Naoki, Higuchi Tsunehiko, Proceedings of the Symposium on Progress in Organic Reactions and Syntheses, 30, (0) 186 - 187,   2004 , Oxidations of alkanes, alkenes, and aromatic rings with pyridine <i>N</i>-oxides are efficiently catalyzed by ruthenium porphyrins under mild conditions. We show here that the oxidation of <i>N</i>-acyl cyclic amines with Ru tetraarylporphyrin dichloride&ndash;2,6-substituted pyridine <i>N</i>-oxides directly gives <i>N</i>-acyl amino acids in modest to good yield via oxidative C&ndash;N bond cleavage. <i>N</i>-Acylazacycloalkanes were converted to <i>N</i>-acyl-&omega;-aminoalkanoic acids. This type of reaction is a novel one in which the C&ndash;N bond is cleaved selectively at the less substituted carbon. Notably, the proline residue in proline-containing peptides was selectively converted to glutamate. A large intramolecular kinetic isotope effect (<i>k</i><sub>H</sub>/<i>k</i><sub>D</sub> = 9.8) was observed in the oxidation of <i>N</i>-benzoyl[2,2,-<i>d</i><sub>2</sub>]pyrrolidine, indicating that the reaction should involve an &alpha;-hydrogen atom abstraction process as the rate-determining step.
  • Dipeptides Containing l-Arginine Analogs: New Lsozyme-Selective Inhibitors of Nitric Oxide Synthase, KOBAYASHI Nobutaka, HIGUCHI Tsunehiko, URANO Yasuteru, KIKUCHI Kazuya, HIROBE Masaaki, NAGANO Tetsuo, Biological and Pharmaceutical Bulletin, 22, (9) 936 - 940,   1999 09 15 , Several L-arginine analogs are known as potent inhibitors of nitric oxide synthase (NOS). We recently synthesized dipeptides containing such amino acids, and found that they are potent and isozyme-selective NOS inhibitors. For example, S-methyl-L-isothiocitrullinyl-L-phenylalanine showed 66-fold selectivity for iNOS over nNOS, while S-methyl-L-isothiocitrullinyl-L-leucine and N<SUP>G</SUP>-nitro-L-argininyl-L-phenylalanine showed 20- and 14-fold selectivity, respectively. Interestingly, S-methyl-L-isothiocitrullinyl-D-phenylalanine showed no selectivity, and S-methyl-L-isothiocitrullinyl-L-phenylalanine showed compective inhibition. These results suggest that each NOS isozyme has a cavity of different size near the C-terminal of the L-arginine binding site, and that the selectivity of inhibitors is due to the differences in the size of the cavity.
  • Inhibitory Effect of Drugs with A Ketone Group on Reduction of Acetohexamide Catalyzed by Carbonyl Reductase from Rabbit Kidney, Imamura Yorishige, Koga Toshihisa, Higuchi Toshiyuki, Otagiri Masaki, Sugino Eiichi, Hibino Satoshi, Annual report of the Faculty of Pharmacy & Pharmaceutical Sciences, Fukuyama University, 16,   1998 , The reduction of acetohexamide catalyzed by carbonyl reductase from rabbit kidney was inhibited by befunolol, moperone, levobunolol, daunorubicin and loxoprofen, which have a ketone group within their chemical structures and are substrates for the enzyme. A significant correlation was obserbed between the common logarithm of Vmax/Km values of enzyme for befunolol, moperone, levobunolol and daunorubicin and the percentage inhibition of the enzyme, confirming that these drugs are competitive substrates of the enzyme with respect to acetoxamide. However, the plot for loxoprofen, a nonsteroidal anti-inflammatory drug with a ketone group, was apparently distant from the regression line obtained. Although nonsteroidal anti-inflammatory drugs with a ketone group such as suprofen and fenbufen were not reduced by the enzyme, they strongly inhibited the reduction of acetohexamide catalyzed by the enzyme.
  • Purification and Properties of Carbonyl Reductase from Rabbit Ridney, Imamura Yorishige, Higuchi Toshiyuki, Nozaki Yoshihide, Sugino Eiichi, Hibino Satoshi, Otagiri Masaki, Annual report of the Faculty of Pharmacy & Pharmaceutical Sciences, Fukuyama University, 12,   1994
  • A Novel Aromatic Hydroxylation of Phenolic Compounds with Cu^<2+>-Ascorbic Acid-O_2 System, URANO Y, Aihara Kazuhiro, Higuchi Tsunehiko, Hirobe Masaaki, J. Pharmacobio-Dyn., 15,   1992
  • Application of Chemical P-450 Model Systems to Study Drug Metabolism. III. : Metabolism of 3-Isobutyryl-2-isopropylpyrazolo[1,5-α]pyridine, NAGATSU Y, HIGUCHI Tsunehiko, HIROBE Masaaki, Chem. Pharm. Bull., 38,   1990 , Oxidation of 3-isobutyryl-2-isopropylpyrazolo[1,5-α]pyridine (IBPP) was carried out with various chemical model systems for cytochrome P-450 in comparison with the liver microsomal system of rats or humans. α-Hydroxylation of side chains and ring hydroxylation at the 6 and 7 positions were the main reactions in both systems. A pattern analysis of products using two dimensional thin layer chromatography was employed to compare the functions of the chemical model systems with those of microsomal systems. The reaction profile of IBPP by the catalyst/Pt-colloid/H_2,O_2 system was most similar to that of human or rat microsomal system. The utility of these chemical models is discussed from the viewpoint of drug metabolism.
  • FACILE PREPARATION OF UNSTABLE METABOLIC INTERMEDIATES : EPOXIDE(S) OF PYRAZOLO[1,5-a]PYRIDINE DERIVATIVES BY THE CYTOCHROME P-450 CHEMICAL MODEL, NAGATSU Y, HIGUCHI Tsunehiko, HIROBE Masaaki, Chem. Pharm. Bull., 37,   1989 , Biomimetic oxidation of bioactive pyrazolo[1,5-a]pyridine derivatives carried out with the chemical model for cytochrome P-450,afforded 6,7-epoxides in relatively high yields, these appear to be chemically unstable precursors of the main metabolites, i__-.e__-., 6,7-dihydro-6,7-diols.
  • 60 VERSATILE CHILAL SYNTHONS FOR VIC-AMINO ALCOHOLS, Ishizuka Tadao, Ishibuchi Seigo, Kunieda Takehisa, Higuchi Tsunehiko, Hirobe Masaaki, Symposium on the Chemistry of Natural Products, symposium papers, 30, (0) 462 - 467,   1988 , The 2-oxazolone moiety has proved of synthetic potential as an excellent leaving group in carboxyl- and phosphoryl-activating processes. This work deals with another synthetic aspects of the heterocycle as a building block for vic-amino・alcohol structures, which are structural units found in a substantial number of bioactive compounds such as enzyme inhibitors, antibiotics and sympathomimetic amines. The synthetic strategy shown in Fig.1 offers versatile routes to a wide variety of vic-amino alcohols in which the key step is regio- and stereoselective introductions of easily replaceable groups (X,Y) to the olefinic moiety of the 2-oxazolone (1), followed by stereospecific and stepwise substitutions with appropriate groups (R^2and R^3). This methodology would be expected to result in predominant formation of threo-derivatives (5), which could be readily converted, if needed, to erythro-configurations (6) by inversion of the hydroxy group via oxazoline intermediates (8 and 10). Enantiomerically pure type 2 synthons were readily obtained by bromo-methoxylation of (+)/(-)-3-ketopiny1-2-oxazolones with new reagent system, Br_2/MeC(OMe)_3/TMSOTf. The reactions were smoothly proceeded to result in highly diastereoelective formation of trans-5-bromo-4-methoxy adducts (2,90%de) which served as common intermediates for biologically significant vic-amino alcohols such as (16), (21) and (24).

Books etc

  • 無機化学, 化学同人,   2011 , ISBN:9784759812541, 共著
  • 薬学のための無機化学, 化学同人,   2005 , ISBN:9784759809886, 共著
  • Rational Design of Fulorescein-based Fluorescence Probes.-Mechanism-based Design of a Maximum Fluorescence Probe for Singlet Oxygen-,   2001
  • Pronounced Effects of Axial Thiolate Ligand on Oxygen Activation by Iron Porphyrin,   1998
  • Polypeptide-bound Porphinatoirons as Cytochrome P-450 Model Compound.,   1988

Conference Activities & Talks

  • 一般性の高いケージドペプチド設計法, 日本薬学会第128年会,   2008
  • 「分子バーコード」としての合成DNAによる個別情報付加, 日本薬学会第128年会,   2008
  • 三次元的に固定した分子内反応補助基のマンガンサレン錯体の酵素類似触媒活性に及ぼす効果, 特定領域研究「協奏機能触媒」第3回公開シンポジウム,   2007
  • ヘム-チオレート錯体によるプロスタグランジンH2の触媒的異性化反応, 平成19年度日本薬学会東海支部例会,   2007
  • 「分子バーコード」としての合成DNAによる個別情報付加, 平成19年度日本薬学会東海支部例会,   2007
  • 化学進化的合成化学によるβ-アミロイド親和性物質の開発, 平成19年度日本薬学会東海支部例会,   2007
  • 環構造を有する新規ポリアミンの合成と活性評価, 平成19年度日本薬学会東海支部例会,   2007
  • Turn-on Fluorescent Probes Targeted to a Hexahistidine Tag Peptide, The 4th Takeda Science Foundation Symposium on PharmaSciences,   2007
  • マンガンサレン錯体への反応補助基導入による活性酸素消去能の高効率化, 第26回メディシナルケミストリーシンポジウム,   2007
  • 反応補助基を導入したマンガンサレン錯体の活性酸素消去活性, 第40回酸化反応討論会,   2007
  • Efficient Isomerization of Prostaglandin H2 Catalyzed by Heme-Thiolate Complexes, The 67th Okazaki Conference Molecular Science and Chemical Biology of Biomolecular Function,,   2007
  • Development of On-chip Fluorescence Assay for Serine/threonine Kinases, 4th International Peptide Symposium,   2007
  • 環構造を有する新規ポリアミン類の合成と活性評価, 第22回生体機能関連化学シンポジウム,   2007
  • 合成DNAを用いた塗料への個別情報付加, 第22回生体機能関連化学シンポジウム,   2007
  • 一般性の高いケージドペプチド設計法, 第22回生体機能関連化学シンポジウム,   2007
  • ヘム-チオレート錯体によるプロスタグランジンH2の触媒的異性化反応, 第22回生体機能関連化学シンポジウム,   2007
  • マンガンサレン錯体のカタラーゼ様活性に及ぼす分子内反応補助基の協奏的効果, 第57回錯体化学討論会,   2007
  • 水素結合に基づく基質認識能を有するポルフィリン金属錯体による位置選択的, 第100回触媒討論会,   2007
  • HTSを目指したセリン・トレオニンキナーゼ蛍光アッセイ法の開発, 日本分析化学会第56年会,   2007
  • 一般性の高いケージドペプチド設計法, 第53回日本薬学会東海支部総会・大会,   2007
  • ヘム-チオレート錯体によるプロスタグランジンH2の効率的異性化反応, 第17回金属の関与する生体関連反応シンポジウム,   2007
  • 膜電位の定量計測を目指したフォトクロミック分子の開発, 日本薬学会第127年会,   2007
  • 光駆動回転分子の創製, 日本薬学会第127年会,   2007
  • セリン・トレオニンキナーゼの効率的蛍光検出法の開発, 日本薬学会第127年会,   2007
  • シトクロムP450化学モデルによるプロスタグランジンH2の異性化反応, 日本薬学会第127年会,   2007
  • ヘムと強い相互作用を行う分子の設計とその抗マラリア活性, 日本薬学会第127年会,   2007
  • Efficient Isomerization of Endoperoxide Catalyzed by Heme-thiolate Complex, The 21st Century COE-RCMS International Conference on Elucidation and Creation of Molecular Functions,   2007
  • Turn-on Fluorescent Probes for Recognition of Specific Peptide Sequence, The 21st Century COE-RCMS International Conference on Elucidation and Creation of Molecular Functions,   2007
  • ヒスタグ配列を認識し発蛍光する蛍光試薬の開発, 平成18年度日本薬学会東海支部例会,   2006
  • ケトイミンの触媒的不斉Strecker反応の開発, 名古屋大学21世紀COEプログラム「物質科学の拠点形成:分子機能の解明と創造」第3回有機化学若手研究会,   2006
  • 特定ペプチド配列を認識し発蛍光する蛍光試薬の開発, 名古屋大学21世紀COEプログラム「物質科学の拠点形成:分子機能の解明と創造」,   2006
  • 環構造を有する新規ポリアミン類の合成とその活性評価, 名古屋大学21世紀COEプログラム「物質科学の拠点形成:分子機能の解明と創造」,   2006
  • ヘムチオレート錯体の触媒するエンドペルオキシドの高速異性化反応-プロスタグランジン異性化酵素との関連-, 名古屋大学21世紀COEプログラム「物質科学の拠点形成:分子機能の解明と創造」,   2006
  • 水素結合に基づく基質認識能を有するポルフィリン金属錯体の合成と位置選択的アルキル鎖酸化, 第39回酸化反応討論会,   2006
  • ヘムチオレート錯体の触媒するエンドペルオキシドの高速異性化反応-プロスタグランジン異性化酵素との関連-, 第39回酸化反応討論会,   2006
  • Novel Fluorescent Probes for Recognition of Specific Peptide Sequence, International Conference of 43rd Japanese Peptide Symposium and 4th Peptide Engineering,   2006
  • Chemoselective Synthesis of Peptide-Porphyrin Conjugate, International Conference of 43rd Japanese Peptide Symposium and 4th Peptide Engineering,   2006
  • Efficient Fluorescence Assay for Serine/Threonine Kinases, International Conference of 43rd Japanese Peptide Symposium and 4th Peptide Engineering Meeting (43JPS-PEM4),   2006
  • ヘムと強い相互作用を行う分子の設計とその抗マラリア活性, バイオ関連化学合同シンポジウム,   2006
  • セリン・トレオニンキナーゼの効率的蛍光検出法の開発, バイオ関連化学合同シンポジウム,   2006
  • 特定ペプチド配列を認識し発蛍光する蛍光試薬の開発, バイオ関連化学合同シンポジウム,   2006
  • 基質認識能を有するルテニウムポルフィリン錯体によるアルキル鎖の位置選択的触媒酸化, バイオ関連化学合同シンポジウム,   2006
  • 環構造を有する新規ポリアミン類の合成と活性評価, 第18回生体機能関連化学若手の会サマースクール,   2006
  • 合成DNAを用いた塗料への個別情報付加, 第18回生体機能関連化学若手の会サマースクール,   2006
  • 特定ペプチド配列の認識を目指した蛍光試薬の開発, 第18回生体機能関連化学若手の会サマースクール,   2006
  • ヘムチオレート錯体の触媒するエンドペルオキシドの高速異性化反応-プロスタグランジンH2異性化酵素との関連-, 第18回生体機能関連化学若手の会サマースクール,   2006
  • ヘムチオレート錯体の触媒するエンドペルオキシドの高速異性化反応-プロスタグランジン異性化酵素との関連-, 第52回日本薬学会東海支部総会・大会,   2006
  • Endoperoxide isomerization catalyzed by a heme-thiolate complex relevant to prostaglandin H2 isomerases, 第16回金属の関与する生体関連反応シンポジウム,   2006
  • Novel fluorescent probes for recognition of specific peptide sequence, 第16回金属の関与する生体関連反応シンポジウム,   2006
  • セリン・スレオニンキナーゼ活性のオンビーズ蛍光検出法の開発, 日本ケミカルバイオロジー研究会第1回年会,   2006
  • ヘムへのスタッキング能と鉄への配位能を兼ね備えた分子の合成と抗マラリア活性, 日本薬学会第126年会,   2006
  • 環構造を有する新規ポリアミン類縁体の合成と機能評価, 日本薬学会第126年会,   2006
  • グアニジノ基をピリジン環に構造変換したアルギニン類似型NOS阻害剤の開発, 日本薬学会第126年会,   2006
  • ヒスタグペプチドの添加により蛍光強度が増大する新規蛍光プローブの開発, 日本薬学会第126年会,   2006
  • ヘムの触媒するプロスタグランジン異性化酵素モデル反応における顕著な軸配位子効果, 日本薬学会第126年会,   2006
  • 任意配列が可能な合成DNAを情報素子として用いた塗装等の個別認証新技術, 日本薬学会第126年会,   2006
  • Staudinger Ligationを用いたPeptide-Porphyrin Conjugateの汎用的合成法の開発, 第8回生命化学研究会シンポジウム,   2006
  • Structural-functional Models of Cytochrome P450 and Catalase, International Chemical Congress of Pacific Basin Societies (PACIFICHEM2005),   2005
  • On-bead Fluorescence Assay for Serine/Threonine Kinases, International Chemical Congress of Pacific Basin Societies (PACIFICHEM2005),   2005
  • Versatile Synthesis of Peptide-Porphyrin Conjugate, International Chemical Congress of Pacific Basin Societies (PACIFICHEM2005),   2005
  • 化学平衡を利用した標的分子に対する低分子受容体のテーラーメード合成, 第24回メディシナルケミストリーシンポジウム,   2005
  • ヘムを標的とする新規抗マラリア薬の合成と活性評価, 第24回メディシナルケミストリーシンポジウム,   2005
  • 化学平衡を利用した標的分子に対する低分子受容体のテーラーメード合成, 第20回生体機能関連化学シンポジウム,   2005
  • ヘムの触媒するプロスタグランジン合成酵素モデル反応における顕著な軸配位子効果, 第20回生体機能関連化学シンポジウム,   2005
  • 反応補助基を導入したシクロペンタン環を骨格に有するマンガンサレン錯体類の合成と活性酸素消去能, 第20回生体機能関連化学シンポジウム,   2005
  • Role of Axial Thiolate Ligand in Cytochrome P450 Catalysis: Chemical Model Approach, US-Japan Conference on Drug Development&Rational Drug Therapy 2005,   2005
  • 化学平衡を利用した標的分子に対する低分子受容体のテーラーメード合成, 第51回日本薬学会東海支部総会・大会,   2005
  • 疎水性官能基導入によるアルギニンアナログのNO合成酵素阻害選択性への効果, 第51回日本薬学会東海支部総会・大会,   2005
  • シトクロムP450配位構造の特性解明及び強力な酸化反応系の開発, 明治薬科大学,   2005
  • 反応補助基を導入したシクロペンタン環を骨格に有するマンガンサレン錯体類の合成と活性酸素消去能, 日本薬学会第125年会,   2005
  • 抗マラリア薬を目指した高いヘム親和性を有する分子の開発, 日本薬学会第125年会,   2005
  • 汎用性の高いペプチドーポルフィリン複合体合成法の開発, 日本薬学会第125年会,   2005
  • 化学平衡を利用した熱力学的最適化による化学合成, 日本薬学会第125年会,   2005
  • セリン・スレオニンキナーゼ活性のオンビーズ蛍光検出法の開発, 日本薬学会第125年会,   2005
  • チオレート配位ヘムによるアルキルヒドロペルオキシドのO-O結合開裂反応解析, 日本薬学会第125年会,   2005
  • 基質認識能を有するポルフィリン金属錯体の合成と位置選択的アルカン酸化, 日本薬学会第125年会,   2005
  • 疎水性官能基導入によるアルギニンアナログのNO合成酵素阻害選択性への効果, 日本薬学会第125年会,   2005
  • セリン・スレオニンキナーゼ活性の蛍光検出法の開発, 第7回生命化学研究会シンポジウム,   2005
  • セリン・スレオニンキナーゼ活性のオンビーズ蛍光検出法の開発, 平成16年度日本薬学会東海支部例会,   2004
  • ヘム酵素に関連した特徴的機能性分子の開発, 日本大学薬学部,   2004
  • シクロペンタン環を骨格に導入したマンガンサレン錯体類の合成と活性酸素消去能, 第37回酸化反応討論会,   2004
  • ルテニウムポルフィリンの触媒するN-アシル環状アミン類のN-アシルアミノ酸への酸化的直接変換反応, 第30回反応と合成の進歩シンポジウム,   2004
  • 基質認識能を有するポルフィリン金属錯体の合成と位置選択的アルカン酸化, 第30回反応と合成の進歩シンポジウム,   2004
  • ルテニウムポルフィリンの触媒するN-アシル環状アミン類のN-アシルアミノ酸への直接変換, 第19回生体機能関連化学シンポジウム,   2004
  • スタウディンガー反応を用いた汎用性の高いペプチド?ポルフィリン複合体合成法の開発, 第19回生体機能関連化学シンポジウム,   2004
  • セリン・スレオニンキナーゼ活性のオンビーズ蛍光検出法の開発, 第19回生体機能関連化学シンポジウム,   2004
  • チオレート配位ヘムによるアルキルヒドロペルオキシドのO-O 結合開裂反応解析, 第19回生体機能関連化学シンポジウム,   2004
  • セリン・スレオニンキナーゼ活性のオンビーズ蛍光検出法の開発, 第19回生体機能関連化学シンポジウム若手フォーラム,   2004
  • 抗マラリア薬を目指した高いヘム親和性を有する分子の開発, 第50回日本薬学会東海支部大会,   2004
  • Staudinger Ligationを用いた汎用性の高いペプチド-ポルフィリン複合体合成法の開発, 第50回日本薬学会東海支部大会,   2004
  • シクロペンタン環を骨格に導入したマンガンサレン錯体類の合成と活性酸素消去能, 第50回日本薬学会東海支部大会,   2004
  • シトクロムP450酵素機能における中心錯体構造の必然性, 京都薬科大学,   2004
  • Staudinger Ligationを用いた汎用性の高いペプチド-ポルフィリン複合体合成法の開発, 第2回次世代を担う有機化学シンポジウム,   2004
  • アシルウレア構造を組み込んだ新規クラウンエーテル類の合成法開発とカルシウムイオン選択的蛍光プローブ構築への応用, 第14回金属の関与する生体関連反応シンポジウム,   2004
  • P450の多様性を支える反応機構, 日本薬学会第124年会,   2004
  • 嵩高い有機塩による分極効果:電場形成酵素機能モデル, 日本薬学会第124年会,   2004
  • シトクロムP450活性種特定を指向した中間体保護型ヘム-チオレート分子の開発, 日本薬学会第124年会,   2004
  • ルテニウムポルフィリン-ピリジンN-オキシド系によるN-アシル環状アミン類の酸化的開裂反応, 日本薬学会第124年会,   2004
  • ルマジン誘導体の蛍光性金属センサー機能とその機構解明, 日本薬学会第124年会,   2004
  • Active Intermediates in Oxidation Reaction Catalyzed by Synthetic Heme-Thiolate Complex Relevant to Cytochrome P450, 3rd International Conference on Porphyrins and Phthalocyanins


  • 補修塗膜及び補修塗装方法, 特願2004-362136
  • 非露出面用塗料組成物及び非露出面塗膜, 特願2004-362130
  • 艶消し塗料組成物及び艶消し塗膜, 特願2004-362125
  • クリヤー塗料組成物及びクリヤー塗膜, 特願2004-362123
  • 着色上塗り塗料組成物及び上塗り塗膜, 特願2004-362121
  • 下塗り塗料組成物及び下塗り塗膜, 特願2004-362120
  • キナーゼ活性検出法, 特願2004-293084
  • 製品製造方法, 特願2004-286558
  • 情報化核酸担持微粒子及びその製造方法, 特願2004-286555
  • 情報化核酸及びこれを用いた情報化核酸組成物, 特願2004-286704

Awards & Honors

  •   2003 03 , The Pharmaceutical Society of Japan, The PSJ Award for Divisional Scientific Promotion

Research Grants & Projects

  • カテナン・ロタキサン構造の導入による生理活性分子の活性制御新手法, Japan Society for the Promotion of Science (JSPS), Grant-in-Aid forChallenging Research (pioneering),   2011 04  - 2013 03
  • 化学進化的合成化学による医薬機能分子の汎用性ある効率的創製, Japan Society for the Promotion of Science (JSPS), Grants-in-Aid for Scientific Research (A),   2008 04  - 2012 03
  • 分子内反応補助基の協奏的効果による酵素類似触媒の高度機能化, MEXT, Grants-in-Aid for Scientific Research on Priority Areas,   2008 04  - 2009 03
  • 新概念に基づく高い効率を目指した光駆動一方向回転分子の開発,   2007 04  - 2009 03
  • 極微量で個別認証を可能にする人工DNA結合微粒子情報素子の開発, Japan Society for the Promotion of Science (JSPS),   2005 04  - 2007 03
  • 官能基集積による協同効果を利用した医薬機能分子の動的創製,   2006  - 2007
  • 医薬開発及び環境浄化への応用に有効な強力酸化触媒反応系の開発,   2000  - 2002
  • ポルフィリン配位構造の特性探求と医薬化学への応用,   1999  - 2001
  • 強力な酸化反応性を有する強靱なRuポルフィリン担持高分子触媒の開発
  • 硫黄配位子への水素結合形式の与える金属-硫黄錯体の電子伝達能への効果

Social Contribution Activities Information

Social Contribution

  • 独立行政法人日本学術振興会科学研究費委員会審査委員, 行政,   2012 12 10  - 2013 11 30 , 独立行政法人日本学術振興会科学研究費の申請に関する審査を行った。
  • 第45回酸化反応討論会の開催, 地域団体・NPO,   2012 04 01  - 2012 12 15 , 第45回酸化反応討論会を、名古屋市立大学病院大ホールで平成24年11月16日−17日に開催した。(実行委員長:樋口恒彦)

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