研究室オリジナルHP

生命有機化学研究室

研究テーマ

有機化学をツールとする生命機能現象の解明と創薬への応用

生命有機化学研究室では合成化学と機器分析の手法を駆使し、生命機能現象を解明するための鍵化合物として主に含共役多重結合化合物を合成し、創薬ならびに応用化学へと繋げる基礎的研究を展開しています。

スタッフ

和田 昭盛

和田 昭盛 教授

担当科目:有機化学I 有機化学II 構造解析学I 機器分析学実習 化学系創薬学特論(大学院)
学位:薬学博士

レチノイド誘導体を用いた生物有機化学的研究を展開しています。具体的には、視覚を司るタンパク質・ロドプシンの発色団としてレチナールが知られており、視覚や脳機能の解明に貢献できるようなレチナール誘導体を設計・合成および生物活性評価をしています。また核内受容体RXRは生活習慣病と密接に関わることから、強力なRXRアゴニストとなり得るレチノイン酸誘導体の開発にも取り組んでいます。

山野 由美子

山野 由美子 准教授

担当科目:有機化学IV 合成化学I 有機化学演習 機器分析学実習 化学系創薬学特論(大学院)
学位:薬学博士

エポキシドの開環方向を制御した天然カロテノイドのバイオミメティック合成を展開しています。また、抗酸化作用や抗肥満作用などの生理作用を調べるためのアナログ合成や、集光アンテナとして機能するカロテノイドの光特性を明らかにするためのアナログの合成、立体構造を明らかにするための天然カロテノイドの全合成研究も行っています。

沖津 貴志

沖津 貴志 講師

担当科目:有機化学II 合成化学II 有機化学演習 機器分析学実習
学位:博士(薬学)

多重結合の特性を生かした複素環合成法について研究しています。具体的には、アルキンやアレン類の反応性を巧みに利用して、医薬品によくみられる芳香族複素環(ベンゾフラン、ピラゾール、イソキサゾールなど)やアミノ酸由来複素環(プロリン誘導体など)の新構築法の開発に取り組んでいます。

研究成果

Okitsu, T.; Nakahigashi, H.; Sugihara, R.; Fukuda, I.; Tsuji, S.; In, Y.; Wada, A.
Silyl Group-Directed 6-exo-dig Iodocyclization of Homopropargylic Carbamates and Amides
Chem. Eur. J. 2018, 24(70), 18638-18642.
DOI: 10.1002/chem.201804794

Shen, Y.-C.; Sasaki, T.; Matsuyama, T.; Yamashita, T.; Shichida, Y.; Okitsu, T.; Yamano, Y.; Wada, A.; Ishizuka, T.; Yawo, H.; Imamoto, Y.
Red-Tuning of Channelrhodopsin Spectrum Using Long Conjugated Retinal Analogues
Biochemistry 2018, 57(38), 5544-5556.
DOI: 10.1021/acs.biochem.8b00583

Chen, H.-F.; Inoue, K.; Ono, H.; Abe-Yoshizumi, R.; Wada, A.; Kandori, H.
Time-resolved FTIR study of light-driven sodium pump rhodopsins
Phys. Chem. Chem. Phys. 2018, 20(26), 17694-17704.
DOI: 10.1039/C8CP02599A

Makino, Y.; Kawamura, I.; Okitsu, T.; Wada, A.; Kamo, N.; Sudo, Y.; Ueda, K.; Naito, A.
Retinal Configuration of ppR Intermediates Revealed by Photoirradiation Solid-State NMR and DFT
Biophys. J. 2018, 115(1), 72-83.
DOI: 10.1016/j.bpj.2018.05.030

Takayama, R.; Kaneko, A.; Okitsu, T.; Tsunoda, S. P.; Shimono, K.; Mizuno, M.; Kojima, K.; Tsukamoto, T.; Kandori, H.; Mizutani, Y.; Wada, A.; Sudo, Y.
Production of a Light-Gated Proton Channel by Replacing the Retinal Chromophore with Its Synthetic Vinylene Derivative
J. Phys. Chem. Lett. 2018, 9(11), 2857-2862.
DOI: 10.1021/acs.jpclett.8b00879

Sato, K.; Yamashita, T.; Ohuchi, H.; Takeuchi, A.; Gotoh, H.; Ono, K.; Mizuno, M.; Mizutani, Y.; Tomonari, S.; Sakai, K.; Imamoto, Y.; Wada, A.; Shichida, Y.
Opn5L1 is a retinal receptor that behaves as a reverse and self-regenerating photoreceptor
Nature Communications 2018, 9, 1255.
DOI: 10.1038/s41467-018-03603-3

Maeda, R.; Hiroshima, M.; Yamashita, T.; Wada, A.; Sako, Y.; Shichida, Y.; Imamoto, Y.
Shift in Conformational Equilibrium Induces Constitutive Activity of G-Protein-Coupled Receptor, Rhodopsin
J. Phys. Chem. B 2018, 122(18), 4838-4843.
DOI: 10.1021/acs.jpcb.8b02819

Yamano, Y.; Masumoto, M.; Takaichi, S.; Wada, A.
Total synthesis of myxol and deoxymyxol stereoisomers and their application to determining the absolute configurations of the natural products
Tetrahedron 2018, 74(13), 1533-1539.
DOI: 10.1016/j.tet.2018.02.018

Sakai, K.; Tsutsui, K.; Yamashita, T.; Iwabe, N.; Takahashi, K.; Wada, A.; Shichida, Y.
Drosophila melanogaster rhodopsin Rh7 is a UV-to-visible light sensor with an extraordinarily broad absorption spectrum
Sci. Rep. 2017, 7, 7349.
DOI: 10.1038/s41598-017-07461-9

Sakane, R.; Kimura, K.; Hirota, Y.; Isizawa, M.; Takagi, Y.; Wada, A.; Kuwahara, S.; Makishima, M.; Suhara, Y.
Synthesis of novel vitamin K derivatives with alkylated phenyl groups introduced at the -terminal side chain and evaluation of their neural differentiation activities
Bioorg. Med. Chem. Lett. 2017, 27(21), 4881-4884.
DOI: 10.1016/j.bmcl.2017.09.038

Yamano, Y.; Sasaki, H.; Wada, A.
Versatile Amine-Promoted Mild Methanolysis of 3,5-Dinitrobenzoates and Its Application to the Synthesis of Colorado Potato Beetle Pheromone
Chem. Pharm. Bull. 2017, 65(10), 940-944.
DOI: 10.1248/cpb.c17-00462

Okitsu, T.; Kobayashi, K.; Kan, R.; Yoshida, Y.; Matsui, Y.; Wada, A.
3-Methylene-4-amido-1,2-diazetidine as a Formal 1,4-Dipole Precursor: Lewis Acid-Catalyzed Nucleophilic Addition with Silylated Nucleophiles
Org. Lett. 2017, 19(17), 4592-4595.
DOI: 10.1021/acs.orglett.7b02194

Okitsu, T.; Matsuyama, T.; Yamashita, T.; Ishizuka, T.; Yawo, H.; Imamoto, Y.; Shichida, Y.; Wada, A.
Alternative Formation of Red-Shifted Channelrhodopsins: Noncovalent Incorporation with Retinal-Based Enamine-Type Schiff Bases and Mutated Channelopsin
Chem. Pharm. Bull. 2017, 65(4), 356-358.

Terai, Y.; Miyagi, R.; Aibara, M.; Mizoiri, S.; Imai, H.; Okitsu, T.; Wada, A.; Takahashi-Kariyazono, S.; Sato, A.; Tichy, H.; Mrosso, H. D. J.; Mzighani, S. I.; Okada, N.
Visual adaptation in Lake Victoria cichlid fishes: depth-related variation of color and scotopic opsins in species from sand/mud bottoms
BMC Evol. Biol. 2017, 17:200.
DOI: 10.1186/s12862-017-1040-x

Kojima, K.; Matsutani, Y.; Yamashita, T.; Yanagawa, M.; Imamoto, Y.; Yamano, Y.; Wada, A.; Hisatomi, O.; Nishikawa, K.; Sakurai, K.; Shichida, Y.
Adaptation of cone pigments found in green rods for scotopic vision through a single amino acid mutation
Proc. Natl. Acad. Sci. U. S. A. 2017, 114(21), 5437-5442.
DOI: 10.1073/pnas.1620010114

Okitsu, T.; Matsuyama, T.; Yamashita, T.; Ishizuka, T.; Yawo, H.; Imamoto, Y.; Shichida, Y.; Wada, A.
Alternative Formation of Red-Shifted Channelrhodopsins: Noncovalent Incorporation with Retinal-Based Enamine-Type Schiff Bases and Mutated Channelopsin
Chem. Pharm. Bull. 2017, 65(4), 356-358.
DOI: 10.1248/cpb.c17-00054

Yamano, Y.; Nishiyama, Y.; Aoki, A.; Maoka, T.; Wada, A.
Total synthesis of lycopene-5,6-diol and -carotene-5’,6’-diol stereoisomers and their HPLC separation
Tetrahedron 2017, 73(15), 2043-2052.
DOI: 10.1016/j.tet.2017.02.048

Kimura, K.; Hirota, Y.; Kuwahara, S.; Takeuchi, A.; Tode, C.; Wada, A.; Osakabe, N.; Suhara, Y.
Synthesis of Novel Synthetic Vitamin K Analogues Prepared by Introduction of a Heteroatom and a Phenyl Group That Induce Highly Selective Neuronal Differentiation of Neuronal Progenitor Cells
J. Med. Chem. 2017, 60(6), 2591-2596.
DOI: 10.1021/acs.jmedchem.6b01717

Shigeta, A.; Ito, S.; Inoue, K.; Okitsu, T.; Wada, A.; Kandori, H.; Kawamura, I.
Solid-State Nuclear Magnetic Resonance Structural Study of the Retinal-Binding Pocket in Sodium Ion Pump Rhodopsin
Biochemistry 2017, 56(4), 543-550.
DOI: 10.1021/acs.biochem.6b00999

Luk, H. L.; Bhattacharyya, N.; Montisci, F.; Morrow, J. M.; Melaccio, F.; Wada, A.; Sheves, M.; Fanelli, F.; Chang, B. S. W.; Olivucci, M.
Modulation of thermal noise and spectral sensitivity in Lake Baikal cottoid fish rhodopsins
Sci. Rep. 2016, 6, 38425.
DOI: 10.1038/srep38425

Okitsu, T.; Ogasahara, M.; Wada, A.
Convergent Synthesis of Dronedarone, an Antiarrhythmic Agent
Chem. Pharm. Bull. 2016, 64(8), 1149-1153.
DOI: 10.1248/cpb.c16-00237

Yanagawa, M.; Kojima, K.; Yamashita, T.; Iwamoto, Y.; Matsuyama, T.; Nakanishi, K.; Yamano, Y.; Wada, A.; Sako, Y.; Shichida, Y.
Origin of the low thermal isomerization rate of rhodopsin chromophore
Sci. Rep. 2015, 5, 11081.
DOI: 10.1038/srep11081

Oshima, K.; Shigeta, A.; Makino, Y.; Kawamura, I.; Okitsu, T.; Wada, A.; Tuzi, S.; Iwasa, T.; Naito, A.
Characterzation of photo-intermediates in the photo-reaction pathways of a bacteriorhodopsin Y185F mutant using in situ photo-irradiation solid-state NMR spectroscopy
Photochem. Photobiol. Sci. 2015, 14(9), 1694-1702.
DOI: 10.1039/c5pp00154d

Katayama, K.; Okitsu, T.; Imai, H.; Wada, A.; Kandori, H.
Identical Hydrogen-Bonding Strength of the Retinal Schiff Base between Primate Green- and Red-Sensitive Pigments: New Insight into Color Tuning Mechanism
J. Phys. Chem. Lett. 2015, 6(7), 1130-1133.
DOI: 10.1021/acs.jpclett.5b00291

Yamano, Y.; Eno, K.; Hikita, Y.; Kurimoto, H.; Wada, A.
Stereocontrolled First Total Syntheses of Salmoxanthin and Deepoxysalmoxanthin
Curr. Org. Synth. 2015, 12(2), 180-188.
DOI: 10.2174/1570179411999141106102507

Yamano, Y.; Ematsu, K.; Kurimoto, H.; Maoka, T.; Wada, A.
Total synthesis of gobiusxanthin stereoisomers and their application to determination of absolute configurations of natural products: revision of reported absolute configuration of epigobiusxanthin
Mar. Drugs 2015, 13(1), 159-172.
DOI: 10.3390/md13010159

Maoka, T.; Yamano, Y.; Wada, A.; Etho, T.; Terada, Y.; Tokuda, H.; Nishino, H.
Oxidative Metabolites of Lycopene and -Carotene in Gac (Momordica cochinchinensis)
J. Agric. Food Chem. 2015, 63(5), 1622-1630.
DOI: 10.1021/jf505008d

Yomoda, H.; Makino, Y.; Tomonaga, Y.; Hidaka, T.; Kawamura, I.; Okitsu, T.; Wada, A.; Sudo, Y.; Naito, A.
Color-Discriminating Retinal Configurations of Sensory Rhodopsin I by Photo-Irradiation Solid-State NMR Spectroscopy
Angew. Chem. Int. Ed. 2014, 53(27), 6960-6964.
DOI: 10.1002/anie.201309258

Yamano, Y.; Maoka, T.; Wada, A.
Synthesis of (3S,3S')- and meso-stereoisomers of alloxanthin and determination of absolute configuration of alloxanthin isolated from aquatic animals
Mar. Drugs 2014, 12(5), 2623-2632.
DOI: 10.3390/md12052623

Okitsu, T.; Nakata, K.; Nishigaki, K.; Michioka, N.; Karatani, M.; Wada, A.
Iodocyclization of Ethoxyethyl Ethers to Ynamides: An Immediate Construction to Benzo[b]furans
J. Org. Chem. 2014, 79(12), 5914-5920. DOI:
DOI: 10.1021/jo500903y

Maeda, R.; Hiroshima, M.; Yamashita, T.; Wada, A.; Nishimura, S.; Sako, Y.; Shichida, Y.; Imamoto, Y.
Single-Molecule Observation of the Ligand-Induced Population Shift of Phdopsin, A G-Protein-Coupled Receptor
Biophys. J. 2014, 106(4), 915-924.
DOI: 10.1016/j.bpj.2014.01.020

Sakane, C.; Okitsu, T.; Wada, A.; Sagami, H.; Shidoji, Y.
Inhibition of lysine-specific demethylase 1 by the acyclic diterpenoid geranylgeranoic acid and its derivatives
Biochem. Biophys. Res. Commun. 2014, 444(1), 24-29.
DOI: 10.1016/j.bbrc.2013.12.144

Sato, S.; Fukagawa, T.; Tachibanaki, S.; Yamano, Y.; Wada, A.; Kawamura, S.
Substrate Specificity and Subcellular Localization of the Aldehyde-Alcohol Redox-coupling Reaction in Carp Cones
J. Biol. Chem. 2013, 288(51), 36589-36597.

Hirota, Y.; Tsugawa, N.; Nakagawa, K.; Suhara, Y.; Tanaka, K.; Uchino, Y.; Takeuchi, A.; Sawada, N.; Kamao, M.; Wada, A.; Okitsu, T.; Okano, T.
Menadione (Vitamin K3) Is a Catabolic Product of Oral Phylloquinone (Vitamin K1) in the Intestine and a Circulating Precursor of Tissue Menaquinone-4 (Vitamin K2) in Rats
J. Biol. Chem. 2013, 288(46), 33071-33080.

Wang, S.; Munro, R. A.; Shi, L.; Kawamura, I.; Okitsu, T.; Wada, A.; Kim, S.-Y.; Jung, K.-H.; Brown, L. S.; Ladizhansky, V.
Solid-state NMR spectroscopy structure determination of a lipid-embedded heptahelical membrane protein
Nature Methods 2013, 10(10), 1007-1012.

Yamano, Y.; Chary, M. V.; Wada, A.
Stereocontrolled First Total Syntheses of Amarouciaxanthin A and B
Org. Lett. 2013, 15(20), 5310-5313.

Wang, S.; Shi, L.; Okitsu, T.; Wada, A.; Brown, L. S.; Ladizhansky, V.
Solid-state NMR 13C and 15N resonance assignments of a seven-transmembrane helical protein Anabaena Sensory Rhodopsin
Biomol. NMR Assign. 2013, 7(2), 253-265.

Furutani, Y.; Okitsu, T.; Reissig, L.; Mizuno, M.; Homma, M.; Wada, A.; Mizutani, Y.; Sudo, Y.
Large Spectral Change due to Amide Modes of a β-Sheet upon the Formation of an Early Photointermediate of Middle Rhodopsin
J. Phys. Chem. B 2013, 117(13), 3449-3458.

Okitsu, T.; Yumitate, S.; Sato, K.; In, Y.; Wada, A.
Substituent Effect of Bis(pyridines)iodonium Complexes as Iodinating Reagents: Control of the Iodocyclization-Oxidation Process
Chem. Eur. J. 2013, 19(16), 4992-4996.