Studies on the Molecular Recognition and Design of Ligands of Olfactory Receptors

• Project/Area Number: 20611018
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Nigata University of Phermacy and Applied Life Sciences
• Principal Investigator: ISHIGURO Masaji Nigata University of Phermacy and Applied Life Sciences, 応用生命科学部, 教授 (10280687)
• Co-Investigator(Kenkyū-buntansha): YONEDA Teruyo 新潟薬科大学, 応用生命科学部, 准教授 (30265714) ; TAMIYA Minoru 新潟薬科大学, 応用生命科学部, 助教 (10468960)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 匂い受容体 / GPCR / フルアゴニスト / CH-π相互作用 / デヒドロエピアンドロステノン / ステロイド / OR7D4 / アンドロステノン / 分子モデリング / アンタゴニスト

Research Abstract

Various odorants are recognized by about 500 kinds of odorant receptors. OR7D4, an odorant receptor binds androstadiene, a steroid derivative. Through modeling of the receptor-ligand complex structure, important residues involved in the ligand binding and the moieties which interact with the residues are selected and the steroid derivatives modified at the D16 portion were synthesized from dehydroepiandrosterone.

Research Products

• [Journal Article] Modification of D-ring Moiety of Steroids-A Novel Palladium Catalyzed Beayer-Villiger Type Rearrangement of Cyclic Silylenol ether Derivatives (2010)
  • Author(s): Minoru Tamiya, Futa Takada, Nobuhisa Isaka, Nahoko Iimura, Masaji Ishiguro
  • Journal Title: Heterocycles 82巻 Pages: 1119-1125
  • Peer Reviewed
• [Journal Article] G.Structure-activity relationships of GPR120 agonists based on a docking simulation. (2010)
  • Author(s): Sun, Q., Hirasawa, A., Hara, T., Kimura, I., Adachi, T., Awaji, T., Ishiguro, M., Suzuki, T., Miyata., N, Tsujimoto
  • Journal Title: Mol.Pharmacol. Volume: 78 Pages: 804-810
  • Peer Reviewed
• [Journal Article] Characterization of the β-D-glucopyranoside binding site of the human bitter taste receptor hTAS2R16 (2010)
  • Author(s): Sakurai, T., Misaka, T., Ishiguro, M., Masuda, K., Sugawara, T., Ito, K., Kobayashi, T., Matsuo, S., Ishimaru, Y., Asakura, T., Abe, K
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 28373-28378
  • Peer Reviewed
• [Journal Article] Engineered mutation of some important amino acids in angiotensin II type1 (AT1) receptor increases the binding affinity of AT1-receptor antagonists. (2010)
  • Author(s): Bhuiyan, M.A., Hossain, M., Ishiguro, M., Nakamura, T., Nagatomo, T.
  • Journal Title: J.Pharmacol.Sci. Volume: 113 Pages: 57-65
  • NAID: 130000251910
  • Peer Reviewed
• [Journal Article] The human bitter taste receptor, hTAS2R16, discriminates slight differences in the configuration of disaccharides. (2010)
  • Author(s): Sakurai, T., Misaka, T., Ueno, Y., Ishiguro, M., Matsuo, S., Ishimaru, Y., Asakura, T., Abe, K
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 402 Pages: 595-601
  • Peer Reviewed
• [Journal Article] Photoactive ligands probing the sweet taste receptor. Design and synthesis of highly potent diaziriny1 D-phenylalanine derivatives. (2010)
  • Author(s): Masuda, K, Koizumi, A., Misaka, T., Hatanaka, Y., Abe, K., Tanaka, T., Ishiguro, M., Hashimoto., M.
  • Journal Title: Bioorg.Med.Chem.Lett. Volume: 20 Pages: 1081-1083
  • Peer Reviewed
• [Journal Article] Bulky high-mannose-type N-glycan blocks the taste-modifying activity of miraculin. (2010)
  • Author(s): Ito, K, Sugawara, T., Koizumi, A., Nakajima, K.I., Shimizu-Ibuka, A., Shiroishi, M., Asada, H., Yurugi-Kobayashi, T., Shimamura, T., Asakura, T., Masuda, K., Ishiguro, M., Misaka, T., Iwata, S.Kobayashi, T., Abe, K.
  • Journal Title: Biochim.Biophys.Acta Volume: 1800 Pages: 986-992
  • Peer Reviewed
• [Journal Article] Functional differentiation of the glycosyltransferases that contribute to the chemical diversity of bioactive flavonol glycosides in grapevines (Vitis vinifera). (2010)
  • Author(s): Ono, E., Homma, Y., Horikawa, M., Kunikane-Doi, S., Imai, H., Takahashi, S., Kawai, Y., Ishiguro, M., Fukui, Y., Nakayama, T.
  • Journal Title: Plant Cell Volume: 22 Pages: 2856-2871
  • Peer Reviewed
• [Journal Article] Anti-Clostridium difficile potential of tetramic acid derivatives from Pseudomonas quorum-sensing autoinducer. (2010)
  • Author(s): Ueda, C., Tateda, K., Horikawa, M., Kimura, S., Ishii, Y., Nomura, K., Yamada, K., Suematsu, T., Inoue, Y., Ishiguro, M., Miyairi, S., Yamaguchi, K.
  • Journal Title: Antimicrob.Agents Chemother Volume: 54 Pages: 683-688
  • Peer Reviewed
• [Journal Article] Structure-activity relationship study on alphal adrenergic receptor antagonists from beer (2009)
  • Author(s): Wakimoto T, Nitta M, Kasahara K, Chiba T, Ye Y, Tsuji K, Kan T, Nukaya H, Ishiguro M, Koike M, Yokoo Y, Suwa Y.
  • Journal Title: Bioorg Med Chem Lett. 19 Pages: 5905-5908
  • Peer Reviewed
• [Journal Article] Local differentiation of sugar donor specificity of flavonoid glycosyltransferase in Lamiales. (2009)
  • Author(s): Noguchi A, Horikawa M, Fukui Y, Fukuchi-Mizutani M, Iuchi-Okada A, Ishiguro M, Kiso Y, Nakayama T, Ono E
  • Journal Title: Plant Cell 21 Pages: 1556-1572
  • NAID: 110009757723
  • Peer Reviewed
• [Journal Article] Binding sites of valsartan, candesartan and losartan with angiotensin II receptor 1 subtype by molecular modeling. (2009)
  • Author(s): Bhuiyan MA, Ishiguro M, Hossain M, Nakamura T, Ozaki M, Miura S, Nagatomo T.
  • Journal Title: Life Sci. 85 Pages: 136-140
  • Peer Reviewed
• [Journal Article] Pseudomonas aeruginosa Las quorum sensing autoinducer suppresses growth and biofilm production in Legionella species. (2009)
  • Author(s): Kimura S, Tateda K, Ishii Y, Horikawa M, Miyairi S, Gotoh N, Ishiguro M, Yamaguchi K.
  • Journal Title: Microbiology 155 Pages: 1934-1939
  • Peer Reviewed
• [Journal Article] Highly fucosylated N-glycan ligands for mannan-binding protein expressed specifically on CD26(DPPVI)isolated from a human colorectal carcinoma cell line, SW1116. (2009)
  • Author(s): Kawasaki N, Lin CW, Inoue R, Khoo KH, Kawasaki N, Ma BY, Oka S, Ishiguro M, Sawada T, Ishida H, Hashimoto T, Kawasaki T
  • Journal Title: Glycobiology 19 Pages: 437-450
  • Peer Reviewed
• [Journal Article] Characterization of chemoreceptive protein binding to an oviposition stimulant using a fluorescent micro-binding assay in a butterfly. (2009)
  • Author(s): Tsuchihara K, Wazawa T, Ishii Y, Yanagida T, Nishida R, Zheng XG, Ishiguro M, Yoshihara K, Hisatomi O, Tokunaga F.
  • Journal Title: FEBS Lett 583 Pages: 345-349
  • Peer Reviewed
• [Journal Article] Characterization of chemoreceptive protein binding to an oviposition stimulant using a fluorescent micro-binding assay in a butterfly. (2009)
  • Author(s): Tsuchihara K, Wazawa T, Ishii Y, Yanagida T, Nishida R, Zheng XG, Ishiguro M, Yoshihara K, Hisatomi O, Tokunaga F.
  • Journal Title: FEBS Lett. 583 Pages: 345-349
  • Peer Reviewed
• [Journal Article] Identification of G protein-coupled receptor 120-selective agonists derived from PPARgamma agonists. (2008)
  • Author(s): Suzuki T, Igari S, Hirasawa A, Hata M, Ishiguro M, Fujieda H, Itoh Y, Hirano T, Nakagawa H, Ogura M, Makishima M, Tsujimoto G, Miyata N.
  • Journal Title: J Med Chem. 51 Pages: 7640-7644
  • Peer Reviewed
• [Journal Article] Crystal structure of squid rhodopsin with intracellularly extended cytoplasmic region. (2008)
  • Author(s): Shimamura T, Hiraki K, Takahashi N, Hori T, Ago H, Masuda K, Takio K, Ishiguro M, Miyno M.
  • Journal Title: J Biol Chem. 283 Pages: 17753-17756
  • Peer Reviewed
• [Journal Article] Mutation of important amino acid residue of Asp104Lys in human beta(1)-adrenergic receptor triggers functional and constitutive inactivation. (2008)
  • Author(s): Hossain M, Ahmed M, Bhuiyan MA, Ishiguro M, Nakamura T, Ozaki M, Nasatomo T.
  • Journal Title: Biol Pharm Bull. 31 Pages: 1517-1522
  • Peer Reviewed
• [Presentation] GPCRの機能構造とリガンド認識 (2011)
  • Author(s): 石黒正路
  • Organizer: 岩田ヒト膜受容体構造プロジェクト 研究成果報告会
  • Place of Presentation: 京都大学
  • Year and Date: 2011-03-24
• [Presentation] Velutinol Aの合成研究 (2011)
  • Author(s): 井坂修久、長谷川篤志、田宮実、石黒正路
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡大学
• [Presentation] パラジウムを用いた新規Baeyer-Villiger型環拡大反応 (2010)
  • Author(s): 田宮実、高田楓太、石黒正路
  • Organizer: 第60回有機合成化学協会関東支部シンポジウム
  • Place of Presentation: 新潟薬科大学(口頭発表)
  • Year and Date: 2010-12-04
• [Presentation] パラジウムを用いた新規Baeyer-Villiger型環拡大反応 (2010)
  • Author(s): 田宮実、高田楓太、石黒正路
  • Organizer: 第60回有機合成化学協会関東支部シンポジウム
  • Place of Presentation: 新潟薬科大学
  • Year and Date: 2010-12-04
• [Presentation] Velutinol Aの合成研究 (2010)
  • Author(s): 井坂修久、長谷川篤志、田宮実、石黒正路
  • Organizer: 第60回有機合成化学協会関東支部シンポジウム
  • Place of Presentation: 新潟薬科大学
  • Year and Date: 2010-12-04
• [Presentation] 味覚および嗅覚受容体が多様な味や匂い物質を認識する分子機構 (2010)
  • Author(s): 石黒正路
  • Organizer: 第7回コンビナトリアル・バイオエンジニアリング会議
  • Place of Presentation: 千里阪急ホテル(大阪)
  • Year and Date: 2010-11-12
• [Presentation] パラジウムを用いた新規Baeyer-Villiger型環拡大反応 (2010)
  • Author(s): 高田楓太、井坂修久、田宮実、石黒正路
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山大(口頭発表)
  • Year and Date: 2010-03-30
• [Presentation] 生物と有機化学のインターフェースとしての創薬化学 (2010)
  • Author(s): 石黒正路
  • Organizer: 日本薬学会第130年会シンポジウム
  • Place of Presentation: 岡山大学(岡山)
  • Year and Date: 2010-03-28
• [Presentation] パラジウムを用いた新規Baeyer-Villiger型環拡大反応 (2010)
  • Author(s): 高田楓太, 井坂修久, 田宮実, 石黒正路
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山大学(岡山)
  • Year and Date: 2010-03-27
• [Presentation] Baeyer-Villiger type rearrangement promoted by bivalent palladium (2010)
  • Author(s): Minoru Tamiya, Futa Takada, Masaii Ishiguro
  • Organizer: International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Honolulu Hawaii
• [Presentation] Velutinol Aの合成研究 (2009)
  • Author(s): 井坂修久、田宮実、米田照代、石黒正路
  • Organizer: 第58回有機合成化学協会関東支部シンポジウム
  • Place of Presentation: 長岡技術科学大学(長岡)
  • Year and Date: 2009-11-28
• [Presentation] 薬物受容体の構造から薬物の働きを理解する (2009)
  • Author(s): 石黒正路
  • Organizer: 第19回日本医療薬学会年会シンポジウム
  • Place of Presentation: 長崎ブリックホール(長崎)
  • Year and Date: 2009-10-25
• [Presentation] Functional Structures of GPCRs for Recognition of Various Ligand Structures (2009)
  • Author(s): 石黒正路
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 2009-10-22
• [Presentation] 化学と生物における構造活性相関研究の役割 (2009)
  • Author(s): 石黒正路
  • Organizer: 第61回生物工学会
  • Place of Presentation: 名古屋大学(名古屋)
  • Year and Date: 2009-09-25
• [Presentation] 機能的リガンド認識のための多様なGPCRの構造 (2009)
  • Author(s): 石黒正路
  • Organizer: 構造活性相関フォーラム2009
  • Place of Presentation: 北里大学(東京)
  • Year and Date: 2009-06-19
• [Presentation] Functional Structures of GPCRs for Recognition of Various Ligand Structures (2009)
  • Author(s): 石黒正路
  • Organizer: 日本学術振興会169委員会第29回研究会
  • Place of Presentation: タワーホール船堀(東京)
  • Year and Date: 2009-05-13
• [Presentation] Structural models for Bradykinin B1 receptor-Ligand Complexes (2008)
  • Author(s): 井坂修久, 安達晃弘, 納富勇輔田宮 実, 米田照代, 石黒正路
  • Organizer: 8^<th> China-Japan joint Symposium on drug Design and Develpoment
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-11-03
• [Presentation] ブラジキニンB1およびB2受容体とリガンドの複合体モデリングによる相互作用の解析 (2008)
  • Author(s): 井坂修久, 安達晃弘, 納富勇輔田宮 実, 米田照代, 石黒正路
  • Organizer: 第36回構造活性相関シンポジウム
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-11-02
• [Remarks] ホームページ等
  • URL: http://www.nupals.ac.jp/~ishiguro-yoneda/Chemical%20Biology%20Lab/Top.html
• [Remarks]
  • URL: http://202.244.210.151/nuphp/KgApp