研究者詳細 - 田中　智博

論文 - 田中　智博

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Amodiaquine Analogs Are Potent Inhibitors of Interleukin-6 Production Induced by Activation of Toll-Like Receptors Recognizing Pathogen Nucleic Acids

Yohei Takenaka, Tomohiro Tanaka, Shotaro Otaki, Azusa Kanbe, Tomoe Morita, Kenta Yokoi, Saki Sekiguchi, Koki Nakamura, Hidetoshi Satoh, Toshifumi Tojo, Fumiaki Uchiumi, Kazuki Kitabatake, Shin Aoki, Mitsutoshi Tsukimoto

Biological and Pharmaceutical Bulletin 47 ( 12 ) 2101 - 2118 2024年12月

Design and Synthesis of Poly(2,2′-Bipyridyl) Ligands for Induction of Cell Death in Cancer Cells: Control of Anticancer Activity by Complexation/Decomplexation with Biorelevant Metal Cations

Chandrasekar Balachandran, Masumi Hirose, Tomohiro Tanaka, Jun Jie Zhu, Kenta Yokoi, Yosuke Hisamatsu, Yasuyuki Yamada, Shin Aoki

Inorganic Chemistry 2023年8月

Post-complexation Functionalization of Cyclometalated Iridium(III) Complexes and Applications to Biomedical and Material Sciences

Shin Aoki, Kenta Yokoi, Yosuke Hisamatsu, Chandrasekar Balachandran, Yuichi Tamura, Tomohiro Tanaka

Topics in Current Chemistry 380 ( 5 ) 2022年10月

Design, Synthesis and Biological Evaluation of Boron‐Containing Macrocyclic Polyamine Dimers and Their Zinc(II) Complexes for Boron Neutron Capture Therapy

Hiroki Ueda, Minoru Suzuki, Yoshinori Sakurai, Tomohiro Tanaka, Shin Aoki

European Journal of Inorganic Chemistry 2022 ( 5 ) 2022年2月

The structure of POMGNT2 provides new insights into the mechanism to determine the functional O ‐mannosylation site on α‐dystroglycan

Rieko Imae, Naoyuki Kuwabara, Hiroshi Manya, Tomohiro Tanaka, Masato Tsuyuguchi, Mamoru Mizuno, Tamao Endo, Ryuichi Kato

Genes to Cells 26 ( 7 ) 485 - 494 2021年7月

Design, Synthesis, and Biological Evaluation of Boron-Containing Macrocyclic Polyamines and Their Zinc(II) Complexes for Boron Neutron Capture Therapy

Hiroki Ueda, Minoru Suzuki, Reiko Kuroda, Tomohiro Tanaka, Shin Aoki

Journal of Medicinal Chemistry 64 ( 12 ) 8523 - 8544 2021年6月

Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro

Kaho Shionoya, Masako Yamasaki, Shoya Iwanami, Yusuke Ito, Shuetsu Fukushi, Hirofumi Ohashi, Wakana Saso, Tomohiro Tanaka, Shin Aoki, Kouji Kuramochi, Shingo Iwami, Yoshimasa Takahashi, Tadaki Suzuki, Masamichi Muramatsu, Makoto Takeda, Takaji Wakita, Koichi Watashi

Frontiers in Microbiology 12 2021年4月

掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers Media SA

Coronavirus disease 2019 (COVID-19) has caused serious public health, social, and economic damage worldwide and effective drugs that prevent or cure COVID-19 are urgently needed. Approved drugs including Hydroxychloroquine, Remdesivir or Interferon were reported to inhibit the infection or propagation of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), however, their clinical efficacies have not yet been well demonstrated. To identify drugs with higher antiviral potency, we screened approved anti-parasitic/anti-protozoal drugs and identified an anti-malarial drug, Mefloquine, which showed the highest anti-SARS-CoV-2 activity among the tested compounds. Mefloquine showed higher anti-SARS-CoV-2 activity than Hydroxychloroquine in VeroE6/TMPRSS2 and Calu-3 cells, with IC₅₀ = 1.28 μM, IC₉₀ = 2.31 μM, and IC₉₉ = 4.39 μM in VeroE6/TMPRSS2 cells. Mefloquine inhibited viral entry after viral attachment to the target cell. Combined treatment with Mefloquine and Nelfinavir, a replication inhibitor, showed synergistic antiviral activity. Our mathematical modeling based on the drug concentration in the lung predicted that Mefloquine administration at a standard treatment dosage could decline viral dynamics in patients, reduce cumulative viral load to 7% and shorten the time until virus elimination by 6.1 days. These data cumulatively underscore Mefloquine as an anti-SARS-CoV-2 entry inhibitor.

DOI： 10.3389/fmicb.2021.651403

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Potential anti-COVID-19 agents, cepharanthine and nelfinavir, and their usage for combination treatment

Hirofumi Ohashi, Koichi Watashi, Wakana Saso, Kaho Shionoya, Shoya Iwanami, Takatsugu Hirokawa, Tsuyoshi Shirai, Shigehiko Kanaya, Yusuke Ito, Kwang Su Kim, Takao Nomura, Tateki Suzuki, Kazane Nishioka, Shuji Ando, Keisuke Ejima, Yoshiki Koizumi, Tomohiro Tanaka, Shin Aoki, Kouji Kuramochi, Tadaki Suzuki, Takao Hashiguchi, Katsumi Maenaka, Tetsuro Matano, Masamichi Muramatsu, Masayuki Saijo, Kazuyuki Aihara, Shingo Iwami, Makoto Takeda, Jane A. McKeating, Takaji Wakita

iScience 24 ( 4 ) 102367 - 102367 2021年4月

Development of metallosupramolecular phosphatases based on the combinatorial self-assembly of metal complexes and organic building blocks for the catalytic hydrolysis of phosphate monoesters

Shin Aoki, Akib Bin Rahman, Yosuke Hisamatsu, Yuya Miyazawa, Mohd Zulkefeli, Yutaka Saga, Tomohiro Tanaka

Results in Chemistry 3 100133 - 100133 2021年1月

Crystal structures of fukutin-related protein (FKRP), a ribitol-phosphate transferase related to muscular dystrophy

Naoyuki Kuwabara, Rieko Imae, Hiroshi Manya, Tomohiro Tanaka, Mamoru Mizuno, Hiroki Tsumoto, Motoi Kanagawa, Kazuhiro Kobayashi, Tatsushi Toda, Toshiya Senda, Tamao Endo, Ryuichi Kato

Nature Communications 11 ( 1 ) 2020年1月

掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Abstract

α-Dystroglycan (α-DG) is a highly-glycosylated surface membrane protein. Defects in the O-mannosyl glycan of α-DG cause dystroglycanopathy, a group of congenital muscular dystrophies. The core M3 O-mannosyl glycan contains tandem ribitol-phosphate (RboP), a characteristic feature first found in mammals. Fukutin and fukutin-related protein (FKRP), whose mutated genes underlie dystroglycanopathy, sequentially transfer RboP from cytidine diphosphate-ribitol (CDP-Rbo) to form a tandem RboP unit in the core M3 glycan. Here, we report a series of crystal structures of FKRP with and without donor (CDP-Rbo) and/or acceptor [RboP-(phospho-)core M3 peptide] substrates. FKRP has N-terminal stem and C-terminal catalytic domains, and forms a tetramer both in crystal and in solution. In the acceptor complex, the phosphate group of RboP is recognized by the catalytic domain of one subunit, and a phosphate group on O-mannose is recognized by the stem domain of another subunit. Structure-based functional studies confirmed that the dimeric structure is essential for FKRP enzymatic activity.

DOI： 10.1038/s41467-019-14220-z

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その他リンク： https://www.nature.com/articles/s41467-019-14220-z

Efficient synthesis of N- and O-linked glycopeptides using acid-labile Boc groups for the protection of carbohydrate moieties

Tomohiro Tanaka, Mika Shiraishi, Akio Matsuda, Mamoru Mizuno

Tetrahedron Letters 60 ( 40 ) 151106 - 151106 2019年10月

Design, synthesis and biological evaluation of low molecular weight CXCR4 ligands. 査読

Sakyiamah MM, Kobayakawa T, Fujino M, Konno M, Narumi T, Tanaka T, Nomura W, Yamamoto N, Murakami T, Tamamura H

Bioorganic & medicinal chemistry 27 ( 6 ) 1130 - 1138 2019年3月

Design, synthesis and biological evaluation of low molecular weight CXCR4 ligands

Sakyiamah MM, Kobayakawa T, Fujino M, KonnoM, Narumi T, Tanaka T, Nomura W, Yamamoto N, Murakami T, Tamamura H

ChemMedChem 8 ( 1 ) 118 - 124 2019年

Design and synthesis of boron containing monosaccharides by the hydroboration of d-glucal for use in boron neutron capture therapy (BNCT). 査読

Itoh T, Tamura K, Ueda H, Tanaka T, Sato K, Kuroda R, Aoki S

Bioorganic & medicinal chemistry 26 ( 22 ) 5922 - 5933 2018年12月

CDP-glycerol inhibits the synthesis of the functional O-mannosyl glycan of α-dystroglycan

Rieko Imae, Hiroshi Manya, Hiroki Tsumoto, Kenji Osumi, Tomohiro Tanaka, Mamoru Mizuno, Motoi Kanagawa, Kazuhiro Kobayashi, Tatsushi Toda, Tamao Endo

Journal of Biological Chemistry 293 ( 31 ) 12186 - 12198 2018年8月

Bivalent 14-mer peptide ligands of CXCR4 with polyproline linkers with anti-chemotactic activity against Jurkat cells 査読

Tomohiro Tanaka, Toru Aoki, Wataru Nomura, Hirokazu Tamamura

JOURNAL OF PEPTIDE SCIENCE 23 ( 7-8 ) 574 - 580 2017年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Interaction of CXCR4 with its endogenous ligand, stromal-cell derived factor-1 (SDF-1)/CXCL12, induces various physiological functions involving chemotaxis. Bivalent ligands with a polyproline helix bearing a cyclic pentapeptide, FC131, were previously shown to have higher binding affinities for CXCR4 than the corresponding monovalent ligands. Bivalent ligands based on a 14-mer peptide T140 derivative with polyproline linkers have been designed and synthesized. The activity of these peptides as well as the effect of bivalency of the ligand on CXCR4 binding has been assessed. The binding affinity of these series of bivalent ligands is increased as the linker length increases up to the 12-/15-mer proline linker. The inhibitory activity against chemotaxis on Jurkat cells also depends on the linker length. The T140-derived bivalent ligands with the 9- and 12-mer proline linkers showed the most effective inhibition against chemotaxis at 1000nM, which is even higher than that of known CXCR4 antagonists in the monomer structure. The effective metastatic inhibition by bivalent T140 derivatives indicates the therapeutic potential. Copyright (c) 2017 European Peptide Society and John Wiley & Sons, Ltd.

DOI： 10.1002/psc.2946

Web of Science

PubMed

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Concise and Versatile Synthesis of Sulfoquinovosyl Acyl Glycerol Derivatives for Biological Applications 査読

Tomohiro Tanaka, Yasuhiro Sawamoto, Shin Aoki

CHEMICAL & PHARMACEUTICAL BULLETIN 65 ( 6 ) 566 - 572 2017年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PHARMACEUTICAL SOC JAPAN

Sulfoquinovosyl acylpropanediol (SQAP), a chemically modified analogue of sulfoquinovosyl acylglycerol (SQAG) that occurs in sea algae, has been reported to show a variety of biological activities, including accumulation in tumor cells and the inhibition of tumor cell growth. We report herein on a new concise and versatile synthesis of SQAP itself and derivatives bearing iodoaryl groups and boronclusters. This method should be useful for the design and synthesis of SQAG/SQAP derivatives for diagnosis and the treatment of cancer and related diseases.

DOI： 10.1248/cpb.c17-00135

Web of Science

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B-11 NMR Probes of Copper(II): Finding and Implications of the Cu2+-Promoted Decomposition of ortho-Carborane Derivatives 査読

Tomohiro Tanaka, Yukiko Nishiura, Rikita Araki, Takaomi Saido, Ryo Abe, Shin Aoki

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY ( 12 ) 1819 - 1834 2016年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-V C H VERLAG GMBH

The development of noninvasive methodologies for the detection of d-block metal ions such as copper (Cu2+), zinc (Zn2+), and manganese (Mn2+) is important for understanding their biological roles and relationship with diseases. We have been interested in the use of B-11 NMR probes for the detection of d-block metal ions, because B-11 is an ultratrace element in living systems. o-Carboranes, which consist of ten boron and two carbon atoms, have been applied to numerous drugs and biological active agents. In this work, we found that the o-carborane-pendant cyclens (L-3-L-5) (cyclen = 1,4,7,10-tetraazacyclododecane) are decomposed in the presence of Mn2+ or Cu2+ in aqueous solution at neutral pH, accompanied by the release of 4-9 equiv. of B(OH)(3). Furthermore, it was found that o-carborane derivatives that contain hydroxyl groups instead of a cyclen unit also undergo decomposition in the presence of Cu2+ and the corresponding complexes such as Cu(bpy) to afford 10 equiv. of B(OH)(3), as confirmed by B-11 NMR spectroscopic analysis and an azomethine-H assay. These reactions are applied to B-11 MRI (magnetic resonance imaging) probes for Cu2+.

DOI： 10.1002/ejic.201600117

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Development of a fluoride-responsive amide bond cleavage device that is potentially applicable to a traceable linker 査読

Yamamoto, J, Maeda, N, Komiya, C, Tanaka, T, Denda, M, Ebisuno, K, Nomura, W, Tamamura, H, Sato, Y, Yamauchi, A, Shigenaga, A, Otaka, A

Tetrahedron 70 5122 - 5127 2014年

Development of a traceable linker containing a thiol-responsive amino acid for the enrichment and selective labelling of target proteins 査読

Jun Yamamoto, Masaya Denda, Nami Maeda, Miku Kita, Chiaki Komiya, Tomohiro Tanaka, Wataru Nomura, Hirokazu Tamamura, Youichi Sato, Aiko Yamauchi, Akira Shigenaga, Akira Otaka

ORGANIC & BIOMOLECULAR CHEMISTRY 12 ( 23 ) 3821 - 3826 2014年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ROYAL SOC CHEMISTRY

A traceable linker that is potentially applicable to identification of a target protein of bioactive compounds was developed. It enabled not only thiol-induced cleavage of the linker for enrichment of the target protein but also selective labelling to pick out the target from contaminated non-target proteins for facile identification.

DOI： 10.1039/c4ob00622d

Web of Science

PubMed

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