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HIGUCHI Tsunehiko

FacultyGraduate School of Pharmaceutical Sciences Department of Bioorganic-inorganic Chemistry
PositionProfessor
Mailhiguchiphar.nagoya-cu.ac.jp
HomepageURLhttp://www.phar.nagoya-cu.ac.jp/hp/ysk/index.html
Birthday
Last Updated :2019/11/30

Researcher Profile and Settings

Degree

  • Ph D, The University of Tokyo

Association Memberships

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

Committee Memberships

  •   1988 04  - 現在, The Chemical Society of Japan, member
  •   1985 08  - 現在, The Pharmaceutical Society of Japan, member

Research Activities

Research Areas

  • Basic chemistry, Organic chemistry, bioorganic chemistry
  • Basic chemistry, Inorganic chemistry, bioinorganic chemistry
  • Pharmacy, Drug development chemistry
  • Pharmacy, Chemical pharmacy

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
  • Photocontrol of Peptide Function: Backbone Cyclization Strategy with Photocleavable Amino Acid, Umezawa, Naoki; Noro, Yuka; Ukai, Kazuhiro; Kato, Nobuki; Higuchi, Tsunehiko, ChemBioChem, 12, (11) 1694 - 1698, 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
  • Structurally designed trans-2-phenylcyclopropylamine derivatives potently inhibit histone demethylase LSD1/KDM1, Mimasu, Shinya; Umezawa, Naoki; Sato, Shin; Higuchi, Tsunehiko; Umehara, Takashi; Yokoyama, Shigeyuki, Biochemistry, 49, (30) 6494 - 6503, 08 , 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
  • Facile synthesis of peptide-porphyrin conjugates: Towards artificial catalase, Umezawa, Naoki; Matsumoto, Nobuyoshi; Iwama, Shinsuke; Kato, Nobuki; Higuchi, Tsunehiko, Bioorg. Med. Chem., 18, (17) 6340 - 6350, 09 , 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
  • Spectroscopic and Mechanistic Studies on Oxidation Reactions Catalyzed by the Functional Model SR Complex for Cytochrome P450: Influence of Oxidant, Substrate, and Solvent, Hessenauer-Ilicheva, Natalya; Franke, Alicja; Wolak, Maria; Higuchi, Tsunehiko; van Eldik, Rudi, Chem.Eur. J., 15, (45) 12447 - 12459, 11 , 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
  • Turn-on fluorescent probe with visible light excitation for labeling of hexahistidine tagged protein, Kamoto, Mie; Umezawa, Naoki; Kato, Nobuki; Higuchi, Tsunehiko, Bioorg. Med. Chem. Lett., 19, (8) 2285 - 2288, 04 , 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
  • Inhibition of γ-Secretase Activity by Helical β-Peptide Foldamers, Imamura, Yuki; Watanabe, Naoto; Umezawa, Naoki; Iwatsubo, Takeshi; Kato, Nobuki; Tomita, Taisuke; Higuchi, Tsunehiko, J. Am. Chem. Soc., 131, (21) 7353 - 7359, 06 , Refereed
  • Design and synthesis of a 4-aminoquinoline-based molecular tweezer that recognizes protoporphyrin IX and iron(iii) protoporphyrin IX and its application as a supramolecular photosensitizer, Yosuke Hisamatsu, Naoki Umezawa, Hirokazu Yagi, Koichi Kato, Tsunehiko Higuchi, Chemical Science, 9, (38) 7455 - 7467, 10 , Refereed
  • Extreme rate acceleration by axial thiolate coordination on the isomerization of endoperoxide catalyzed by iron porphyrin: relevance to prostaglandin H2 isomerase catalysis, Yamane, Takehiro; Makino, Kohei; Umezawa, Naoki; Kato, Nobuki; Higuchi, Tsunehiko, Angew. Chem. Int. Ed., 47, (34) 6438 - 6440, Refereed
  • Potent Antimalarial Activity of Two Arenes Linked with Triamine Designed To Have Multiple Interactions with Heme, Yosuke Sakata, Kosuke Yabunaka, Yuko Kobayashi, Hirohisa Omiya, Naoki Umezawa, Hye-Sook Kim, Yusuke Wataya, Yoshimi Tomita, Yosuke Hisamatsu, Nobuki Kato, Hirokazu Yagi, Tadashi Satoh, Koichi Kato, Haruto Ishikawa, Tsunehiko Higuchi, ACS Medicinal Chemistry Letters, 9, (10) 980 - 985, 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
  • Array-based fluorescence assay for serine/threonine kinases using specific chemical reaction, Akita, Shoji; Umezawa, Naoki; Kato, Nobuki; Higuchi, Tsunehiko, Bioorg. Med. Chem., 16, (16) 7788 - 7794, 08 15 , 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 Versatile Strategy for the Synthesis of Crown Ether-Bearing Heterocycles: Discovery of Calcium-Selective Fluoroionophore, Aoki, Yuko; Umezawa, Naoki; Asano, Yuko; Hatano, Keiichiro; Yano, Yuki; Kato, Nobuki; Higuchi, Tsunehiko, Bioorg. Med. Chem., 15, (22) 7108 - 7115, 11 15 , Refereed
  • Novel Probes Showing Specific Fluorescence Enhancement on Binding to Hexahistidine Tag, Kamoto, Mie; Umezawa, Naoki; Kato, Nobuki; Higuchi, Tsunehiko, Chem.-Eur. J., 14, (26) 8004 - 8012, 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
  • Enhanced Catalase-like Activity of Manganese Salen Complexes in Water: Effect of Three-dimensionally Fixed Auxiliary, Watanabe, Yoritada; Namba, Azusa; Umezawa, Naoki; Kawahata, Masatoshi; Yamaguchi, Kentaro; Higuchi, Tsunehiko, Chem. Commun., (47) 4958 - 4960, 12 , 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
  • Selective recognition and detection of biomacromolecules utilizing chemical property of amino acid or peptide, Umezawa Naoki, Akita Shoji, Kamoto Mie, Higuchi Tsunehiko, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 127, (12) 1915 - 1925, 12 , Refereed
  • Active site geometry of a novel aminopropyltransferase for biosynthesis of hyperthermophile-specific branched-chain polyamine, Ryota Hidese, Ka Man Tse, Seigo Kimura, Eiichi Mizohata, Junso Fujita, Naoki Umezawa, Tsunehiko Higuchi, Tadayuki Imanaka, Tsuyoshi Inoue, Shinsuke Fujiwara, FEBS Journal, 284, (21) 3684 - 3701, 11 , Refereed
  • Development and crystallographic evaluation of histone H3 peptide with N-terminal serine substitution as a potent inhibitor of lysine-specific demethylase 1, Yuichi Amano, Masaki Kikuchi, Shin Sato, Shigeyuki Yokoyama, Takashi Umehara, Naoki Umezawa, Tsunehiko Higuchi, Bioorganic and Medicinal Chemistry, 25, (9) 2617 - 2624, 05 , Refereed
  • Role of Thiolate Ligand in Spin State and Redox Switching in the Cytochrome P450 Catalytic Cycle, Hiroshi Suzuki, Kanako Inabe, Yoshinori Shirakawa, Naoki Umezawa, Nobuki Kato, Tsunehiko Higuchi, Inorganic Chemistry, 56, (8) 4245 - 4248, 04 , Refereed
  • Activation of lysine-specific demethylase 1 inhibitor peptide by redox-controlled cleavage of a traceless linker, Yuichi Amano, Naoki Umezawa, Shin Sato, Hisami Watanabe, Takashi Umehara, Tsunehiko Higuchi, Bioorganic {?&} Medicinal Chemistry, 25, (3) 1227 - 1234, 02 , Refereed
  • Design, Synthesis and Evaluation of New Type of L-Amino Acids Containing Pyridine Moiety as Nitric Oxide Synthase Inhibitor, Ijuin, Ryosuke; Umezawa, Naoki; Higuchi, Tsunehiko, Bioorg. Med. Chem., 14, (10) 3563 - 3570, 05 , Refereed
  • Naturally occurring branched-chain polyamines induce a crosslinked meshwork structure in a giant DNA, Akira Muramatsu, Yuta Shimizu, Yuko Yoshikawa, Wakao Fukuda, Naoki Umezawa, Yuhei Horai, Tsunehiko Higuchi, Shinsuke Fujiwara, Tadayuki Imanaka, Kenichi Yoshikawa, Journal of chemical Physics, 145, (23) , 12 , Refereed
  • On-Bead Fluorescence Assay for Serine/Threonine Kinases, Akita, Shoji; Umezawa, Naoki; Higuchi, Tsunehiko, Org. Lett., 7, (25) 5565 - 5568, 12 , Refereed
  • Design of new extraction surfactants for membrane proteins from peptide-gemini surfactants (PG-surfactants), Masahide Shibata, Shuhei Koeda, Tomoyasu Noji, Keisuke Kawakami, Yuya Ido, Yuichi Amano, Naoki Umezawa, Tsunehiko Higuchi, Takehisa Dewa, Shigeru Itoh, Nobuo Kamiya, and Toshihisa Mizuno, Bioconjugate Chemistry, 27, (10) 2469 - 2479, 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
  • Structurally Diverse Polyamines: Solid-Phase Synthesis and Interaction with DNA, Naoki Umezawa, Yuhei Horai, Yuki Imamura, Makoto Kawakubo, Mariko Nakahira, Nobuki Kato, Akira Muramatsu, Yuko Yoshikawa, Kenichi Yoshikawa, Tsunehiko Higuchi, ChemBioChem, 16, (12) 1811 - 1819, 08 , Refereed
  • 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, J. Am. Chem. Soc., 127, (3) 834 - 835, 01 , Refereed
  • Identification of a novel aminopropyltransferase involved in the synthesis of branched-chain polyamines in hyperthermophiles, Kazuma Okada, Ryota Hidese, Wakao Fukuda, Masaru Niitsu, Koichi Takao, Yuhei Horai, Naoki Umezawa, Tsunehiko Higuchi, Tairo Oshima, Yuko Yoshikawa, Tadayuki Imanaka, Shinsuke Fujiwara, Journal of Bacteriology, 196, (10) 1866 - 1876, 05 , Refereed
  • Mechanistic studies on the binding of nitric oxide to a synthetic heme-thiolate complex relevant to cytochrome P450, Franke, Alicja; Stochel, Grazyna; Suzuki, Noriyuki; Higuchi, Tsunehiko; Okuzono, Kimiko; van Eldik, Rudi, J. Am. Chem. Soc., 127, (15) 5360 - 5375, 04 , 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 γ-Secretase Inhibition by β-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
  • Multiple Active Intermediates in Oxidation Reaction Catalyzed by Synthetic Heme-thiolate Complex Relevant to Cytochrome P450, Suzuki, Noriyuki; Higuchi, Tsunehiko; Nagano, Tetsuo, J. Am. Chem. Soc., 124, (32) 9622 - 9628, 08 , Refereed
  • Welcome to SRM2008, Higuchi Tsunehiko, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 128, Refereed
  • Effect of three-dimensionally fixed auxiliary to manganese Salen on its catalase-like activity and peroxidase-like activity, Noritake Yukinobu, Watanabe Yoritada, Namba Azusa, Kato Nobuki, Umezawa Naoki, Higuchi Tsunehiko, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 128, Refereed
  • [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
  • Efficient fluorescence assay for serine/threonine kinases, Umezawa Naoki, Akita Shoji, Higuchi Tsunehiko, DRUGS OF THE FUTURE, 32, 23 - 24, 07 , Refereed
  • Vibronic Coupling between Soret and Higher Energy Excited States in Iron(II) Porphyrins: Raman Excitation Profiles of A2g Modes in the Soret Region, Egawa, Tsuyoshi; Suzuki, Noriyuki; Dokoh, Takashi; Higuchi, Tsunehiko; Shimada, Hideo; Kitagawa, Teizo; Ishimura, Yuzuru, J. Phys. Chem. A, 108, (4) 568 - 577
  • Synthesis of New Bulky Tetraarylphosphonium, Tetraarylborate and Their Salt, Matsumoto, Kaya; Hatano, Keiichiro; Umezawa, Naoki; Higuchi, Tsunehiko, Synthesis, (13) 2181 - 2185
  • Catalytic and Asymmetric Epoxidation by Novel D4-Symmetric Chiral Porphyrin Derived from C2-Symmetric Diol, Nakagawa, Hiroshi; Sei, Yoshihisa; Yamaguchi, Kentaro; Nagano, Tetsuo; Higuchi, Tsunehiko, J. Mol. Cat. A:Chemical, 219, (2) 221 - 226
  • Electronic Effects on Enantioselectivity in the Epoxidation Catalyzed by D4-Symmetric Chiral Porphyrins, Nakagawa, Hiroshi; Sei, Yoshihisa; Yamaguchi, Kentaro; Nagano, Tetsuo; Higuchi, TsunehikoFrom Tetrahedron: Asymmetry (2004), 15(24), 3861-3867. | Language: English, Database: CAPLUS, Tetrahedron: Asym., 15, (24) 3861 - 3867
  • Reversible and competitive inhibition of enteropeptidase by 1-trans-Epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64), Matsushima, Masashi; Yahagi, Naohisa; Ichinose, Masao; Miki, Kazumasa; Omata, Masao; Higuchi, Tsunehiko; Inoue, Hideshi; Takahashi, Takayuki; Takahashi, Kenji, Biomed. Res., 22, (4) 207 - 210
  • Bioimaging of nitric oxide with fluorescent indicators based on the rhodamine chromophore, Kojima, Hirotatsu; Hirotani, Miki; Nakatsubo, Naoki; Kikuchi, Kazuya; Urano, Yasuteru; Higuchi, Tsunehiko; Hirata, Yasunobu; Nagano, Tetsuo, Anal. Chem., 73, (9) 1967 - 1973
  • 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
  • Intramolecular Fluorescence Resonance Energy Transfer System with Coumarin Donor Included in β-Cyclodextrin, Takakusa, Hideo; Kikuchi, Kazuya; Urano, Yasuteru; Higuchi, Tsunehiko; Nagano, Tetsuo, Anal. Chem., 73, (5) 939 - 942
  • 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
  • A new thioether-ligated iron porphyrin as a model of a protonated form of P450 active site, Dokoh T, Suzuki N, Higuchi T, Urano Y, Kikuchi K, Nagano T., J. Inorg. Biochem., 82, (1-4) 127 - 132
  • 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
  • Highly Zinc-Selective Fluorescent Sensor Molecules Suitable for Biological Applications, Hirano, Tomoya; Kikuchi, Kazuya; Urano, Yasuteru; Higuchi, Tsunehiko; Nagano, Tetsuo, J. Am. Chem. Soc., 122, (49) 12399 - 12400
  • Synthesis and superoxide dismutase activity of novel iron complexes, Tamura, Masakazu; Urano, Yasuteru; Kikuchi, Kazuya; Higuchi, Tsunehiko; Hirobe, Masaaki; Nagano, Tetsuo, J. Organomet. Chem., 611, (1-2) 586 - 592
  • Superoxide dismutase activity of iron(II)TPEN complex and its derivatives, Tamura, Masakazu; Urano, Yasuteru; Kikuchi, Kazuya; Higuchi, Tsunehiko; Hirobe, Masaaki;Nagano, Tetsuo, Chem. Pharm. Bull., 48, (10) 1514 - 1518
  • Development of a Time-Resolved Fluorometric Detection System Using Diffusion-Enhanced Energy Transfer, Koresawa, Mitsunori; Kikuchi, Kazuya; Mizukami, Shin; Kojima, Hirotatsu; Urano, Yasuteru; Higuchi, Tsunehiko; Nagano, Tetsuo, Anal. Chem., 72, (20) 4904 - 4907
  • Fluorescent indicators for nitric oxide based on rhodamine chromophore, Kojima, Hirotatsu; Hirotani, Miki; Urano, Yasuteru; Kikuchi, Kazuya; Higuchi, Tsunehiko; Nagano, Tetsuo, Tetrahedron Lett., 41, (1) 69 - 72
  • 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
  • Remarkable Axial Thiolate Ligand Effect on the Oxidation of Hydrocarbons by Active Intermediate of Iron Porphyrin and Cytochrome P450, Ohno T, Suzuki N, Dokoh T, Urano Y, Kikuchi K, Hirobe M, Higuchi T, Nagano T., J. Inorg. Biochem., 82, (1-4) 123 - 125
  • 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
  • Imaging of caspase-3 activation in HeLa cells stimulated with etoposide using a novel fluorescent probe, Mizukami, Shin; Kikuchi, Kazuya; Higuchi, Tsunehiko; Urano, Yasuteru; Mashima, Tetsuo; Tsuruo, Takashi; Nagano, Tetsuo, FEBS Lett., 453, (3) 356 - 360
  • 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
  • Novel Fluorscent Probes for Singlet Oxygen, Umezawa, Naoki; Tanaka, Kumi; Urano, Yasuteru; Kikuchi, Kazuya; Higuchi, Tsunehiko; Nagano, Tetsuo, Angew. Chem. Int. Ed., 38, (19) 2899 - 2901
  • 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
  • Direct evidence of NO production in rat hippocampus and cortex using a new fluorescent indicator: DAF-2 DA, Kojima, Hirotatsu; Nakatsubo, Naoki; Kikuchi, Kazuya; Urano, Yasuteru; Higuchi, Tsunehiko; Tanaka, Junji; Kudo, Yoshihisa; Nagano, Tetsuo, NeuroReport, 9, (15) 3345 - 3348
  • Selective deoxygenation of heteroaromatic N-oxides with olefins catalyzed by ruthenium porphyrin, Nakagawa, Hiroshi; Higuchi, Tsunehiko; Kikuchi, Kazuya; Urano, Yasuteru; Nagano, Tetsuo, Chem. Pharm. Bull., 46, (10) 1656 - 1657
  • 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
  • Selective Quinone Formation by Aromatic Oxidation with Heteroaromatic N-Oxide Catalyzed by Ruthenium Porphyrin, Higuchi, Tsunehiko; Satake, Chika; Hirobe, Masaaki, J. Am. Chem. Soc., 117, 8879 - 8880
  • 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
  • The Highly Efficient Oxidation of Olefins, Alcohols, Sulfides and Alkanes with Heteroaromatic N-oxides Catalyzed by Ruthenium Porphyrins, Ohtake, Hiro; Higuchi, Tsunehiko; Hirobe, Masaaki, Heterocycles, 40, (2) 867 - 903
  • 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
  • Identification of Novel Sugar, 4-Amino-4, 6-dideoxy-2-O-methylmannose in the lipopolysaccharide of Vibrio cholerae Ol Serotype Ogawa, Ito, Teruyo; Higuchi, Tsunehiko; Hirobe, Masaaki; Hiramatsu, Keiichi; Yokota, Takeshi, Carbohyd. Res., 256, 113 - 128
  • 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
  • Heterolytic O-O Bond Cleavage of Peroxy Acid and Effective Alkane Hydroxylation in Hydrophobic Solvent Mediated by an Iron Porphyrin Coordinated by Thiolate Anion as a Model for Cytochrome P-450, Higuchi, Tsunehiko; Shimada, Kousei; Maruyama, Naho; Hirobe, Masaaki, J. Am. Chem. Soc., 115, 7551 - 7552
  • Oxygen Activation by Iron(III) Porphyrin/NaBH4/Me4N. OH System as Cytochrome P-450 Model-Oxygenation of Olefin, N-Dealkylation of Tertiary Amine, Oxidation of Sulfide, and Oxidative Cleavage of Ether Bond, Mori, Takashi; Santa, Tomofumi;Higuchi, Tsunehiko; Mashino, Tadahiko; Hirobe, Masaaki, Chem. Pharm. Bull., 41, (2) 292 - 295
  • Unusual Substituent Effects on the hydroxylation of Phenols by Cu2+-Ascorbic Acid-O2 System, Gamma-Radiolysis, and Microsomes, Urnao, Yasuteru; Higuchi, Tsunehiko; Hirobe, Masaaki, Biochem Biophys Res Commun., 192, 568 - 574
  • 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
  • The Selectivities and The Machanism on Highly Efficient Epoxidation of Olefins with 2, 6-Disubstituted Pyridine N-Oxides Catalyzed by Ruthenium Porphyrin, Ohtake, Hiro; Higuchi, Tsunehiko; Hirobe, Masaaki, Tetrahedron Lett., 33, 2521 - 2524
  • 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
  • Highly Efficient Oxygen Transfer Reactionsfrom Various Heteroaromatic N-Oxides to Olefins, Alcohols, and Sulfides Catalyzed by Ruthenium Porphyrin., Higuchi, Tsunehiko; Ohtake, Hiro; Hirobe, Masaaki, Tetrahedron Lett., 32, (50) 7435 - 7438
  • 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
  • Activation of carboxyl groups by diphenyl 2-oxo-3-oxazolinylphosphonate. Facile preparation of versatile reagents, 3-acyl-2-oxazolones, Kunieda, Takehisa; Higuchi, Tsunehiko; Abe, Yoshihiro; Hirobe, Masaaki, Tetrahedron, 39, (20) 3253 - 3260
  • Highly selective acylation of amines and alcohols by poly(3-acyl-2-oxazolone), Kunieda, Takehisa; Higuchi, Tsunehiko; Abe, Yoshihiro; Hirobe, Masaaki, Tetrahedron Lett., 23, (11) 1159 - 1160
  • A new reagent for activating carboxyl groups: diphenyl 2-oxo-3-oxazolinylphosphonate, Kunieda, Takehisa; Abe, Yoshihiro; Higuchi, Tsunehiko; Hirobe, Masaaki, Tetrahedron Lett., 22, (13) 1257 - 1258
  • 3-Acyl- and 3-alkoxycarbonyl-2-oxazolones and their homopolymers as amino-protecting reagents, Kunieda, Takehisa; Higuchi, Tsunehiko; Abe, Yoshihiro; Hirobe, Masaaki, Tetrahedron Lett., 21, (32) 3065 - 3066
  • Inhibition of FAD-dependent lysine-specific demethylases by chiral polyamine analogues, Naoki Umezawa, Kasumi Tsuji, Shin Sato, Masaki Kikuchi, Hisami Watanabe, Yuhei Horai, Masashi Yamaguchi, Yosuke Hisamatsu, Takashi Umehara, Tsunehiko Higuchi, RSC Advances, 8, 36895 - 36902, Refereed
  • Polyoxygenated seco -cyclohexenes and other constituents from Uvaria valderramensis, Allan Patrick G. Macabeo, Peter Yuosef M. Rubio, Tsunehiko Higuchi, Naoki Umezawa, Christian Faderl, Simon Budde, Porferio S. Bangcaya, Grecebio Jonathan D. Alejandro, Biochemical Systematics and Ecology, 71, 200 - 204, Refereed
  • Efficient oxidation of ethers with pyridine N-oxide catalyzed by ruthenium porphyrins, Nobuki Kato, Yu Hamaguchi, Naoki Umezawa and Tsunehiko Higuchi, Journal of of Porphyrins and Phthalocyanines, 27, (1~3) 411 - 416, Refereed

Misc

  • 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 ,

    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.

    We planned to construct the 10-oxa-tricyclo[5.3.1.03,8]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.

    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.

    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.

  • Inevitable Cytochrome P450 Coordination Structure for Enzyme Function : Chemical Model Approach to Elucidation of the Axial Ligand Effect, HIGUCHI Tsunehiko, Journal of Synthetic Organic Chemistry, Japan, 67, (2) 134 - 142,   2009 02 01 , 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 H2 (PGH2) is catalytically isomerized to prostacyclin or thromboxane A2 by cytochrome P450s. We investigated the isomerization mechanism of PGH2 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–pyridine N-oxide system is an exceptionally potent and efficient oxidizing one for unactivated alkanes, and so on. Ru porphyrin with substrate-recognition sites (1) is expected to be superior to simple Ru porphyrin in both selectivity and efficiency. 1H-NMR study showed that substrate 2 (tetradecane form), 3 (dodecane form) well makes 1:1 complex with 1 by multiple hydrogen bonding. By the addition of 2,6-dichloropyridine N-oxide, 2, 3 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 N-oxides are efficiently catalyzed by ruthenium porphyrins under mild conditions. We show here that the oxidation of N-acyl cyclic amines with Ru tetraarylporphyrin dichloride–2,6-substituted pyridine N-oxides directly gives N-acyl amino acids in modest to good yield via oxidative C–N bond cleavage. N-Acylazacycloalkanes were converted to N-acyl-ω-aminoalkanoic acids. This type of reaction is a novel one in which the C–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 (kH/kD = 9.8) was observed in the oxidation of N-benzoyl[2,2,-d2]pyrrolidine, indicating that the reaction should involve an α-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 NG-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.
  • Improved Nitric Oxide Detection Using 2,3-Diaminonaphthalene and Its Applicatio 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, Biological and Pharmaceutical Bulletin, 21, (12) 1247 - 1250,   1998 12 01 , A specific and sensitive detection method for nitric oxide (NO) in living cells and tissue culture systems is required in the search for novel NO synthase (NOS) inhibitors. We have improved a fluorometric determination with 2, 3-diaminonaphthalene (DAN) by the addition of 2-phenyl-4, 4, 5, 5-tetramehylimidazoline-3-oxide-1-oxyl (PTIO) as an oxidant to form NO2 from NO. This method is 3 times more sensitive than that without PTIO, and is suitable for examining the NOS-inhibitory activity of large numbers of test compounds using a 96-well micropolate reader. The improved method was applied to N-monomethyl-L-arginine (L-NMMA) as a known inhibitor and the derivatives of 2-phenyl-1, 2-benzisoselenazol-3(2H)-one as teat compounds in order to investigate the effect of these compounds on NO production from activated rat aortic smooth muscle cells. The results obtained indicate that this method is suitable for the rapid assay of large numbers of test compounds.
  • Optimum Conditions for the ^<13>C-Phenylalanine Breath Test, ISHII Toshihiro, TAKATORI Kazuhiko, IIDA Katsumi, HIGUCHI Teruhiko, OHSHIMA Akihiko, NARUSE Hiroshi, KAJIWARA Masahiro, Chemical and Pharmaceutical Bulletin, 46, (8) 1330 - 1332,   1998 08 15 , We have conducted optimizaiton studies to develop a superior 13C-phenylalanine breath test for the diagnosis of liver disease. First, we examined the optimum 13C-labeling position in phenylalanine for use in a breath test based on infrared spectroscopic detection of 13CO2 in exhaled air. L-[1-13C]Phenylalanine gave the best result. Next, a suitable dosage to give a short peak time (the time expressed in minutes as which 13CO2 excretion is maximal) after administration was determined. The 13CO2/12CO2 ratio in exhaled air after administration of 100 mg/body of L-[1-13C]phenylalanine peaked sharply at 15 min. We also examined the effect of food on the hepatic metabolism of L-[1-13C]phenylalanine. We found that a fasting period of over 7 h before the test resulted in a higher 13CO2 peak excretion. The peak appeared sooner than that in the 13C-phenacetin breath test and, therefore, the 13C-phenylalanine breath test appears preferable for the rapid evaluation of hepatic function.
  • 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.
  • Thiopalmitic Acid-Mediated Fe(III)-Nitrilotriacetate Reduction and Lipid Peroxidation, TANAKA Mitsuo, TAKADA Kimihiko, HIGUCHI Toshiyuki, NAKAGAWA Mitsuo, Biological and Pharmaceutical Bulletin, 19, (5) 678 - 682,   1996 05 15 , The mechanism of the antioxidant action of thiopalmitic acid (SH-Pal) was examined in an in vitro system measuring ferric (Fe(III))-nitrilotriacetate (NTA)- and Fe(III)-NTA/ascorbic acid (AsA)-induced lipid peroxidation of rat liver phospholipid liposomes and microsomes. The extent of lipid peroxidation was determined by measuring thiobarbituric acid reactive substances (TBARS). SH-Pal and glutathione (GSH) scarcely stimulated the Fe(III)-NTA-induced lipid peroxidation in contrast with the mode of action, being similar to those produced by reducing-agent antioxidants such as cysteine and AsA. SH-Pal reduced iron similar to the action produced by AsA and cysteine, but not that of GSH under the same conditions. Also, the reduction of iron by SH-Pal did not exhibit a pH dependency. Similarly, microsomal lipid peroxidation and oxygen consumption induced by Fe(III)-NTA/AsA were inhibited by the addition of SH-Pal in a time and dose dependent fashion, but GSH and cysteine exhibited a lower protective action. Time course studies on TBARS formation and oxygen consumption indicated the ability of SH-Pal to inhibit initiation and propagation reactions. Moreover, the microsomal lipid peroxidation induced by Cumene hydroperoxide (CumOOH) was progressively suppressed by the addition of increasing amounts of SH-Pal.These findings suggest that the antioxidant action of SH-Pal is partly due to complete reduction of iron at a faster rate and inhibition of oxygen consumption during the progress of the peroxidation. Further, SH-Pal has a protective action against free radical damage by hydroperoxy radical.
  • Effects of Methyl 9(or 10)-Hydroxy-10(or 9)-mercaptostearate and Hexadecanethioic S-Acid on Cupric Ion-or 2,2-Azo-bis(2-amidinopropane) Dihydrochloride (AAPH)-Induced Oxidation of Low Density Lipoprotein, TANAKA Mitsuo, TAKADA Kimihiko, HIGUCHI Toshiyuki, NAKAGAWA Mitsuo, MURASE Masayuki, TOBINAGA Seisho, Biological and Pharmaceutical Bulletin, 19, (5) 692 - 696,   1996 05 15 , The preventive effects of two antioxidants, methyl 9(or 10)-hydroxy-10(or 9)-mercaptostearate (SH-S) and hexadecanethioic S-acid (thiopalmitic acid, SH-Pal) against the oxidative modification of low density lipoproteins (LDL) induced by cupric ion or a water soluble initiator of peroxyl radicals, 2, 2-azobis(2-amidinopropane) dihydrochloride (AAPH), were studied by measuring thiobarbituric acid-reactive substances (TBARS). SH-S acted as an effective antioxidant in the oxidative modification of LDL induced by either cupric ion or AAPH. Interestingly, SH-S completely inhibited the formation of fluorescence products and decreased both the fluorescence and α-tocopherol content in LDL induced by cupric ion, and reduced 1, 1-diphenyl 2-picrylhydrazyl (DPPH) used as a stable free radical model. The antioxidative effect was effectively prevented by the addition of increasing amounts of N-ethylmalemide (NEM) to the system. SH-Pal also inhibited the cupric ion-induced LDL oxidation, but showed little inhibitory effect on the AAPH-induced LDL oxidation. Moreover, SH-Pal was reduced to palmitic acid during the AAPH-induced LDL oxidation.These findings indicate that SH-S protects against oxidative damage of LDL in vitro, and that it acts as a free radical in peroxidation. In addition, this study shows that SH-Pal doesn't act as an efficient antioxidant in AAPH-induced lipid peroxidation.
  • Purifiation and Catalytic Properties of a Novel Acetohexamide-Reducing Enzyme from Rabbit Heart, IMAMURA Yorishige, RYU Akio, KOGA Toshihisa, HIGUCHI Toshiyuki, OTAGIRI Masaki, NOZAWA Masako, AKITA Hiroyuki, The Journal of Biochemistry, 119, (4) 648 - 652,   1996 04 01 , An enzyme catalyzing the metabolic reduction of acetohexamide [4-acetyl-N-(cyclohexylcarbamoyl)benzenesulfonamide], an oral antidiabetic drug, was purified to homogeneity from the cytosolic fraction of rabbit heart. The molecular mass of the purified enzyme was estimated to be 110 kDa by gel filtration and nondenaturing PAGE and 28 kDa by SDS-PAGE, suggesting that the enzyme is composed of four identical-size subunits. 4-Benzoylpyridine and p-nitroacetophenone, typical substrates of carbonyl reductase [EC 1. 1. 1. 184], were not reduced by the enzyme. Of drugs with a ketone group tested, only acetohexamide was a good substrate of the enzyme. The enzyme effectively reduced analogs substituted with various alkyl groups instead of the cyclohexyl group in acetohexamide, although it had little or no ability to reduce analogs substituted with various alkyl groups instead of the methyl group in acetohexamide. The enzyme was inhibited not only by quercetin, a well-known inhibitor of carbonyl reductase, but also by phenobarbital, a potent inhibitor of aldehyde reductase [EC 1. 1. 1. 2]. These results indicate that the enzyme purified from rabbit heart is a novel enzyme responsible for the reduction of acetohexamide and its analogs.
  • 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.
  • INCREASING 5-LIPOXYGENASE INHIBITORY ACTIVITIES BY OXIDATIVE CONVERSION OF O-METHOXYPHENOLS TO CATECHOLS USING A Cu^<2+> - ASCORBIC ACID - O_2 SYSTEM, AIHARA K., HIGUCHI Tsunehiko, HIROBE Masaaki, Chem. Pharm. Bull., 38,   1990 , Several complicated o-methoxyphenols were oxidized with high selectivity to catechols by a Cu^<2+>- ascorbic acid-O_2 system. In this way, the RBL-1 5-lipoxygenase inhibitory activities of o-methoxyphenols were greatly invreased. [6]-Norgingerol (4), a novel compound derived from [6]-gingerol (3), shows promise as a lead compound for new drugs vecause of its high inhibitory potency (IC_<50>=5.0×10^<-8>M).
  • "METABOLIC ACTIVATION" OF o-METHOXYPHENOLS VIA O-DEMETHYLATION WITH A Cu^<2+> -ASCORBIC ACID-O_2 SYSTEM AS A FUNCTIONAL MODEL OF CYTOCHROME P-450, AIHARA K., HIGUCHI Tsunehiko, HIROBE Masaaki, J. Pharmacobio-Dyn., 13,   1990
  • 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.
  • Stereoselective Reduction of Acetohexamide in Cytosol of Rabbit Liver, IMAMURA Y., KOJIMA Yuichiro, HIGUCHI Toshiyuki, AKITA Hiroyuki, OISHI Takeshi, OTAGIRI Masaki, J. Pharmacobio-Dyn., 12,   1989 , The stereoselective reduction of acetohexamide, an oral antidiabetic drug, was studied by using the cytosol of rabbit liver. A major metabolite of acetohexamide was isolated in 41.5% yield from the enzyme reaction mixture, and identified as (-)-hydroxyhexamide by techniques including the melting point, thin-layer chromatography, infrared spectrometry and optical rotation. The enantiomeric purity of (-)-hydroxyhexamide was determined on the basis of the proton nuclear magnetic resonance (400 MHz) spectrum of ester (diastereomer) derived by the reaction of (-)-hydroxyhexamide with (R)-(+)-α-methoxy-α-trifluoromethylphenylacetyl chloride. The (-)-hydroxyhexamide isolated from the enzyme reaction mixture was almost 100% in that enantiomeric form. The metabolic reduction of acetohexamide in the cytosol of rabbit liver appeared to be catalyzed by some enzymes with the same stereoselectivity.
  • o_2-cu^<2+>-ASCORBIC ACID : A NOVEL OXIDATION SYSTEM FOR THE HIGHLY SELECTIVE O-CEALKYLATION OF 2-ALKOXYPHENOLS, AIHARA K., Higuchi Tsunehiko, Hirobe Masaaki, Chem. Pharm. Bull, 36,   1988 , The novel oxidation system "O_2-Cu<2+>-ascorbic acid" is a selective reagent for the oxidative O-dealkyation of 2-alkoxyphenols and affords catechols in good yield.
  • 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).
  • 3-Alkoxycarbonyl-2-oxazolones and Their Homopolymers as Highly Preservable Amino-Protecting Reagents. tert-Butoxycarbonylation and Benzyloxycarbonylation of Amino Groups, KUNIEDA TAKEHISA, HIGUCHI TSUNEHIKO, ABE YOSHIHIRO, HIROBE MASAAKI, Chemical & pharmaceutical bulletin, 32, (6) 2174 - 2181,   1984 06 25 , Highly preservable amino protecting reagents derived from the 2-oxazolone moiety as a common activating mediator have been developed. 3-Alkoxycarbonyl-2-oxazolones serve as easily handled reagents for amino protection, including tert-butoxycarbonylation, benzyloxycarbonylation, p-methoxybenzyloxycarbonylation, methoxycarbonylation and ethoxycarbonylation. For example, high yield N-protection of α-amino acids has been smoothly performed by the use of 3-tert-butoxycarbonyl [Boc-Ox] and 3-benzyloxycarbonyl-2-oxazolones [Cbz-Ox] in aqueous solution at room temperature. A series of homopolymers, poly (3-alkoxycarbonyl-2-oxazolone), is readily obtainable by radical-initiated chain reaction of the corresponding 4,5-unsubstituted oxazolone monomers (except for the tert-butoxy derivative, which failed to give polymeric compounds), and these were successfully used for amino protection as well. Use of the polymer reagents greatly simplifies the purification procedure, though a longer reaction time is required.

Books etc

  • Polypeptide-bound Porphinatoirons as Cytochrome P-450 Model Compound.,   1988
  • Pronounced Effects of Axial Thiolate Ligand on Oxygen Activation by Iron Porphyrin,   1998
  • Rational Design of Fulorescein-based Fluorescence Probes.-Mechanism-based Design of a Maximum Fluorescence Probe for Singlet Oxygen-,   2001
  • 薬学のための無機化学, 化学同人,   2005 , ISBN:978-4-7598-0988-6, 共著
  • 無機化学, 化学同人,   2011 , ISBN:978-4-7598-1254-1, 共著

Conference Activities & Talks

  • 「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
  • 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
  • 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
  • Efficient Isomerization of Endoperoxide Catalyzed by Heme-thiolate Complex, The 21st Century COE-RCMS International Conference on Elucidation and Creation of Molecular Functions,   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
  • 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
  • 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
  • 光駆動回転分子の創製, 日本薬学会第127年会,   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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Development of On-chip Fluorescence Assay for Serine/threonine Kinases, 4th International Peptide Symposium,   2007
  • Efficient Isomerization of Prostaglandin H2 Catalyzed by Heme-Thiolate Complexes, The 67th Okazaki Conference Molecular Science and Chemical Biology of Biomolecular Function,,   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
  • 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
  • Turn-on Fluorescent Probes Targeted to a Hexahistidine Tag Peptide, The 4th Takeda Science Foundation Symposium on PharmaSciences,   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
  • 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
  • 「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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Efficient Fluorescence Assay for Serine/Threonine Kinases, International Conference of 43rd Japanese Peptide Symposium and 4th Peptide Engineering Meeting (43JPS-PEM4),   2006
  • Chemoselective Synthesis of Peptide-Porphyrin Conjugate, International Conference of 43rd Japanese Peptide Symposium and 4th Peptide Engineering,   2006
  • Novel Fluorescent Probes for Recognition of Specific Peptide Sequence, International Conference of 43rd Japanese Peptide Symposium and 4th Peptide Engineering,   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
  • 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-, 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Role of Axial Thiolate Ligand in Cytochrome P450 Catalysis: Chemical Model Approach, US-Japan Conference on Drug Development&Rational Drug Therapy 2005,   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
  • 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
  • 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24回メディシナルケミストリーシンポジウム,   2005
  • Versatile Synthesis of Peptide-Porphyrin Conjugate, 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
  • Structural-functional Models of Cytochrome P450 and Catalase, International Chemical Congress of Pacific Basin Societies (PACIFICHEM2005),   2005
  • 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
  • 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
  • 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
  • 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
  • P450の多様性を支える反応機構, 日本薬学会第124年会,   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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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,   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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Active Intermediates in Oxidation Reaction Catalyzed by Synthetic Heme-Thiolate Complex Relevant to Cytochrome P450, 3rd International Conference on Porphyrins and Phthalocyanins

Patents

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

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 , Tsunehiko Higuchi
  • 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 , Tsunehiko Higuchi
  • 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 , Tsunehiko Higuchi
  • 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 , Tsunehiko Higuchi
  • 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
  • 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 , Tsunehiko Higuchi
  • 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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