研究者詳細 - 阿部　洋

論文 - 阿部　洋

分割表示 248 件中 81 - 100 件目／全件表示 >>

Design and Synthesis of Cyclopropane Congeners of Resolvin E2, an Endogenous Proresolving Lipid Mediator, as Its Stable Equivalents 査読有り

Hayato Fukuda, Ryuta Muromoto, Yuuki Takakura, Kohei Ishimura, Ryutaro Kanada, Daichi Fushihara, Makoto Tanabe, Kotaro Matsubara, Toru Hirao, Koki Hirashima, Hiroshi Abe, Mitsuhiro Arisawa, Tadashi Matsuda, Satoshi Shuto

Organic Letters 18 巻 ( 24 ) 頁： 6224 - 6227 2016年12月

掲載種別：研究論文（学術雑誌）

© 2016 American Chemical Society. Lipid chemical mediator resolvins with highly potent anti-inflammatory activity can be leads to develop novel anti-inflammatory drugs; however, they are unstable in oxygen due to their characteristic polyunsaturated structures. To solve the problem, CP-RvE2 has been designed and synthesized in which the cis-olefin of RvE2 was replaced with a cyclopropane. CP-RvE2s were much more stable than RvE2 against autoxidation and equipotent or more potent than RvE2. CP-RvE2s were successfully identified as stable equivalents of RvE2.

DOI： 10.1021/acs.orglett.6b02612

Scopus

researchmap

Catalytic Conversion of Lipophilic Substrates by Phase constrained Enzymes in the Aqueous or in the Membrane Phase 査読有り

Marcus Cebula. Ilke Simek Turan, Birgitta Sjodin, Madhuranayaki Thulasingam, Joseph Brock, Volodymyr Chmyrov, Jerker Widengren, Hiroshi Abe, Bengt Mannervik, Jesper Haeggstrom, Agnes Rinaldo-Matthis, Engin Akkaya, Ralf Morgenstern

Scientific Reports 6 巻頁： 38316 2016年12月

Design and Synthesis of Cyclopropane Congeners of Resolvin E2, an Endogenous Proresolving Lipid Mediator, as Its Stable Equivalents 査読有り

Organic Letters 18 巻頁： 6224-6227 2016年11月

Chemical Reactivity Window Determines Prodrug Efficiency toward Glutathione Transferase Overexpressing Cancer Cells 査読有り

van Gisbergen Marike W., Cebula Marcus, Zhang Jie, Ottosson-Wadlund Astrid, Dubois Ludwig, Lambin Philippe, Tew Kenneth D., Townsend Danyelle M., Haenen Guido R. M. M., Drittij-Repders Marie-Jose, Saneyoshi Hisao, Araki Mika, Shishido Yuko, Ito Yoshihiro, Arner Elias S. J., Abe Hiroshi, Morgenstern Ralf, Johansson Katarina

MOLECULAR PHARMACEUTICS 13 巻 ( 6 ) 頁： 2010 - 2025 2016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：Molecular Pharmaceutics

Glutathione transferases (GSTs) are often overexpressed in tumors and frequently correlated to bad prognosis and resistance against a number of different anticancer drugs. To selectively target these cells and to overcome this resistance we previously have developed prodrugs that are derivatives of existing anticancer drugs (e.g., doxorubicin) incorporating a sulfonamide moiety. When cleaved by GSTs, the prodrug releases the cytostatic moiety predominantly in GST overexpressing cells, thus sparing normal cells with moderate enzyme levels. By modifying the sulfonamide it is possible to control the rate of drug release and specifically target different GSTs. Here we show that the newly synthesized compounds, 4-acetyl-2-nitro-benzenesulfonyl etoposide (ANS-etoposide) and 4-acetyl-2-nitro-benzenesulfonyl doxorubicin (ANS-DOX), function as prodrugs for GSTA1 and MGST1 overexpressing cell lines. ANS-DOX, in particular, showed a desirable cytotoxic profile by inducing toxicity and DNA damage in a GST-dependent manner compared to control cells. Its moderate conversion of 500 nmol/min/mg, as catalyzed by GSTA1, seems hereby essential since the more reactive 2,4-dinitrobenzenesulfonyl doxorubicin (DNS-DOX) (14000 nmol/min/mg) did not display a preference for GSTA1 overexpressing cells. DNS-DOX, however, effectively killed GSTP1 (20 nmol/min/mg) and MGST1 (450 nmol/min/mg) overexpressing cells as did the less reactive 4-mononitrobenzenesulfonyl doxorubicin (MNS-DOX) in a MGST1-dependent manner (1.5 nmol/min/mg) as shown previously. Furthermore, we show that the mechanism of these prodrugs involves a reduction in GSH levels as well as inhibition of the redox regulatory enzyme thioredoxin reductase 1 (TrxR1) by virtue of their electrophilic sulfonamide moiety. TrxR1 is upregulated in many tumors and associated with resistance to chemotherapy and poor patient prognosis. Additionally, the prodrugs potentially acted as a general shuttle system for DOX, by overcoming resistance mechanisms in cells. Here we propose that GST-dependent prodrugs require a conversion rate "window" in order to selectively target GST overexpressing cells, while limiting their effects on normal cells. Prodrugs are furthermore a suitable system to specifically target GSTs and to overcome various drug resistance mechanisms that apply to the parental drug.

DOI： 10.1021/acs.molpharmaceut.6b00140

Chemical reactivity window determines prodrug efficiency towards glutathione transferase overexpressing cancer cells 査読有り

Marie van Gisbergen, Marcus Cebula, Jie Zhang, Astrid Ottosson-Wadlund, Ludwig Dubois, Philippe Lambin, Kenneth D. Tew, Danyelle Townsend, Guido Haenen, Marie-Jose Drittij-Reijnders, Hisao Saneyoshi, Mika Araki, Yuko Shishido, Yoshihiro Ito, Elias Arner, Hiroshi Abe, Ralf Morgenstern, Katarina Johansson

Molecular Pharmaceutics 13 巻頁： 2010-2025 2016年4月

Diastereoselective Synthesis of 6 ''-(Z)- and 6 ''-(E)-Fluoro Analogues of Anti-hepatitis B Virus Agent Entecavir and Its Evaluation of the Activity and Toxicity Profile of the Diastereomers 査読有り国際誌

Kumamoto Hiroki, Fukano Misato, Nakano Tomohiko, Iwagami Keito, Takeyama Chiaki, Kohgo Satoru, Imoto Shuhei, Amano Masayuki, Kuwata-Higashi Nobuyo, Aoki Manabu, Abe Hiroshi, Mitsuya Hiroaki, Fukuhara Kiyoshi, Haraguchi Kazuhiro

JOURNAL OF ORGANIC CHEMISTRY 81 巻 ( 7 ) 頁： 2827 - 2836 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：Journal of Organic Chemistry

A method for the diastereoselective synthesis of 6″-(Z)- and 6″-(E)-fluorinated analogues of the anti-HBV agent entecavir has been developed. Construction of the methylenecyclopentane skeleton of the target molecules has been accomplished by radical-mediated 5-exo-dig cyclization of the selenides 6 and 15 having the phenylsulfanylethynyl structure as a radical accepting moiety. In the radical reaction of the TBS-protected precursor 6, (Z)-anti-12 was formed as a major product. On the other hand, TIPS-protected 15 gave (E)-anti-12. The sulfur-extrusive stannylation of anti-12 furnished a mixture of geometric isomers of the respective vinylstannane, whereas benzoyl-protected 17 underwent the stannylation in the manner of retention of configuration. Following XeF2-mediated fluorination, introduction of the purine base and deoxygenation of the resulting carbocyclic guanosine gave the target (E)- and (Z)-3 after deprotection. Evaluation of the anti-HBV activity of 3 revealed that fluorine-substitution at the 6″-position of entecavir gave rise to a reduction in the cytotoxicity in HepG2 cells with retention of the antiviral activity.

DOI： 10.1021/acs.joc.6b00105

Effect of sigma-pi conjugation between Si-Si bond and pyridine ring in tris(trimethylsilyl) silylpyridine on its spectroscopic property and SN2 reaction with methyl iodide 査読有り

Ichinose Wataru, Abe Hiroshi, Shuto Satoshi

ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 251 巻 2016年3月

Effect of sigma-pi conjugation between Si-Si bond and pyridine ring in tris(trimethylsilyl) silylpyridine on its spectroscopic property and SN2 reaction with methyl iodide

Ichinose Wataru, Abe Hiroshi, Shuto Satoshi

ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 251 巻 2016年3月

Rolling Circle Translation of Circular RNA in Living Human Cells 査読有り

Abe Naoko, Matsumoto Ken, Nishihara Mizuki, Nakano Yukiko, Shibata Aya, Maruyama Hideto, Shuto Satoshi, Matsuda Akira, Yoshida Minoru, Ito Yoshihiro, Abe Hiroshi

SCIENTIFIC REPORTS 5 巻頁： 16435 2015年11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：Scientific Reports

We recently reported that circular RNA is efficiently translated by a rolling circle amplification (RCA) mechanism in a cell-free Escherichia coli translation system. Recent studies have shown that circular RNAs composed of exonic sequences are abundant in human cells. However, whether these circular RNAs can be translated into proteins within cells remains unclear. In this study, we prepared circular RNAs with an infinite open reading frame and tested their translation in eukaryotic systems. Circular RNAs were translated into long proteins in rabbit reticulocyte lysate in the absence of any particular element for internal ribosome entry, a poly-A tail, or a cap structure. The translation systems in eukaryote can accept much simpler RNA as a template for protein synthesis by cyclisation. Here, we demonstrated that the circular RNA is efficiently translated in living human cells to produce abundant protein product by RCA mechanism. These findings suggest that translation of exonic circular RNAs present in human cells is more probable than previously thought.

DOI： 10.1038/srep16435

Nickel-catalyzed Suzuki-Miyaura coupling of a tertiary iodocyclopropane with wide boronic acid substrate scope: Coupling reaction outcome depends on radical species stability 査読有り

Keisuke Yotsuji, Naoyuki Hoshiya, Takaaki Kobayashi, Hayato Fukuda, Hiroshi Abe, Mitsuhiro Arisawa, Satoshi Shuto

Advanced Synthesis and Catalysis 357 巻 ( 5 ) 頁： 1022 - 1028 2015年3月

掲載種別：研究論文（学術雑誌）

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. We describe a nickel-catalyzed Suzuki-Miyaura arylation of a tertiary iodocyclopropane with arylboronic acids; this is an efficient and convergent strategy for providing various enantioenriched arylcyclopropanes with a quaternary stereogenic center. This is the first metal-catalyzed coupling between a tertiary alkyl electrophile and a wide range of aromatics, including heteroaromatics. We found that the outcome of the Ni-catalyzed coupling with halides as electrophiles was dependent on the stability of the radical species formed during the reaction. The use of tert-butyl alcohol (t-BuOH) as the reaction solvent was very effective, because of its stability under the radical-generating reaction conditions.

DOI： 10.1002/adsc.201401000

Scopus

researchmap

Nanostructured RNAs for RNA Interference 査読有り

Nakashima Yuko, Abe Naoko, Ito Yoshihiro, Abe Hiroshi

RNA INTERFERENCE: CHALLENGES AND THERAPEUTIC OPPORTUNITIES 1218 巻頁： 17 - 36 2015年

記述言語：英語掲載種別：論文集(書籍)内論文出版者・発行元：RNA Interference: Challenges and Therapeutic Opportunities

We synthesized three types of nanostructured RNAs that induce RNA interference (RNAi): branched RNAs, dumbbell-shaped RNA, and circular double-stranded RNAs. All three nanostructured RNAs were transformed into double-stranded RNA of approximately 20 base pairs when they were treated with nuclease enzymes such as Dicer. These dsRNA species induced gene silencing when they are were introduced into mammalian cells.

DOI： 10.1007/978-1-4939-1538-5_2

Phosphorylated 5-ethynyl-2 '-deoxyuridine for advanced DNA labeling 査読有り

Seo Siyoong, Onizuka Kazumitsu, Nishioka Chieko, Takahashi Eiki, Tsuneda Satoshi, Abe Hiroshi, Ito Yoshihiro

ORGANIC & BIOMOLECULAR CHEMISTRY 13 巻 ( 15 ) 頁： 4589 - 4595 2015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：Organic and Biomolecular Chemistry

The representative DNA-labeling agent 5-ethynyl-2′-deoxyuridine (EdU) was chemically modified to improve its function. Chemical monophosphorylation was expected to enhance the efficiency of the substrate in DNA polymerization by circumventing the enzymatic monophosphorylation step that consumes energy. In addition, to enhance cell permeability, the phosphates were protected with bis-pivaloyloxymethyl that is stable in buffer and plasma, and degradable inside various cell types. The phosphorylated EdU (PEdU) was less toxic than EdU, and had the same or a slightly higher DNA-labeling ability in vitro. PEdU was also successfully applied to DNA labeling in vivo. In conclusion, PEdU can be used as a less toxic DNA-labeling agent for studies that require long-term cell survival or very sensitive cell lines.

DOI： 10.1039/c5ob00199d

Synthesis of 3’,4’-difluoro-3’-deoxyribonucleosides and its evaluation of the biological activities: Discovery of a novel type of anti-HCV agent 3’,4’-difluorocordycepin 査読有り

Hisashi Shimada, Kazuhiro Haraguchi, Kumi Hotta, Tomoko Miyaike, Yasuyuki Kitagawa, Hiromichi Tanaka, Ryutaro Kaneda, Hiroshi Abe, Satoshi Shuto, Kyoko Mori, Youki Ueda, Nobuyuki Kato, Robert Snoeck, Graciela Andrei, an Balzarini

Bioorganic & Medicinal Chemistry 22 巻 ( 21 ) 頁： 6174 - 6182 2014年11月

Fluorogenic probes using 4-substituted-2-nitrobenzenesulfonyl derivatives as caging groups for the analysis of human glutathione transferase catalyzed reactions (vol 138, pg 7326, 2013) 査読有り

Aya Shibata, Yukiko Nakano, Mika Ito, Mika Araki, Jie Zhang, Yasuhiko Yoshida, Satoshi Shuto, Bengt Mannervik, Ralf Morgenstern, Yoshihiro Ito, Hiroshi Abe

ANALYST 139 巻 ( 17 ) 頁： 4382 - 4382 2014年9月

Conformationally Restricted GABA with Bicyclo[3.1.0]hexane Backbone as the First Highly Selective BGT‑1 Inhibitor 査読有り

Takaaki Kobayashi, Akihiro Suemasa, Arisa Igawa, Soichiro Ide, Hayato Fukuda, Hiroshi Abe, Mitsuhiro Arisawa, Masabumi Minami, Satoshi Shuto

ACS Medicinal Chemistry Letters 5 巻 ( 8 ) 頁： 889 - 893 2014年8月

Sustained delivery of siRNA from dopamine-coated stainless steel surfaces (vol 9, pg 6753, 2013)

Joddar Binata, Albayrak Aydin, Kang Jeonghwa, Nishihara Mizuki, Abe Hiroshi, Ito Yoshihiro

ACTA BIOMATERIALIA 10 巻 ( 8 ) 頁： 3811 - 3811 2014年8月

Development of Molecular Probe Targeting on Glutathion Transferase 査読有り

Ito Mika, Shuto Satoshi, Ito Yoshihiro, Abe Hiroshi

JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 72 巻 ( 7 ) 頁： 822 - 831 2014年7月

記述言語：日本語出版者・発行元：Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry

Glutathione S-transferase (GST) are phase II enzymes that catalyze the nucleophilic attack of glutathione (GSH) to a wide range of hydrophobic and electrophilic compounds. GST is of high clinical interest in inflammation, pathophysiology and tumor drug resistance. In addition, GST is known to highly express in cancer cells. Therefore, we tried to develop new luminescent probes that can detect and image GST expression in living cells. Recently, we found that the electrophilic centre in the dinitrobenzenesulfonamide derivative is attacked by GSH and that this reaction is catalyzed by GST releasing the strong fluorophore. Based on this knowledge, we synthesized fluorescent probe, 19F MKI probe, and bioluminogenic probe. The fluorescent probe and kinetic parameters for purified GST were giving a rate enhancement of 106 compared with the nonenzymatic reaction. In addition, fluorescent probe successfully image GST in living cells. The fluorescent probe is potentially useful reagent for detection of GST activity in living cells. 19F MKI and bioluminogenic probes were synthesized using 4-acetyl-2-nitrobenzenesulfonyl group. 19F MKI probe exhibited a peak shift of 19F MRI signal and fluorescence enhancement in a bimodal way in response to GST activity. Bioluminogenic probe provided strong bioluminescence from GST activity. Moreover, both probes were successfully applied to the monitoring of GST expression in living E. coli cells. Successful detection of GST activity in living cells could be very useful for identifying tumor cells that overexpress GSTs.

DOI： 10.5059/yukigoseikyokaishi.72.822

Web of Science

Scopus

researchmap

Automatic Pseudorotaxane Formation Targeting on Nucleic Acids Using a Pair of Reactive Oligodeoxynucleotides 査読有り

Onizuka Kazumitsu, Nagatsugi Fumi, Ito Yoshihiro, Abe Hiroshi

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 136 巻 ( 20 ) 頁： 7201 - 7204 2014年5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：Journal of the American Chemical Society

Here we report a novel method to form a pseudorotaxane architecture using only a pair of reactive oligodeoxyribonucleotides (ODNs), which we designed and synthesized, and then performed the pseudorotaxane formation reaction with both DNA and RNA oligonucleotides. The reaction proceeded smoothly without any extra reagents at 37°C and pH 7.2, leading to the formation of a stable complex on a denaturing polyacrylamide gel. Interestingly, the pseudorotaxane was formed with the cyclized ODN reversibly by the slipping process. This new pseudorotaxane formation represents a promising method for developing new DNA nanotechnologies and antisense oligonucleotides. © 2014 American Chemical Society.

DOI： 10.1021/ja5018283

Development of rapid DNA templated reaction based on nucleophilic aromatic substitution reaction

Shibata Aya, Abe Hiroshi, Uzawa Takanori, Nakano Yukiko, Shuto Satoshi, Ito Yoshihiro

ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 247 巻 2014年3月

Synthesis of active siRNA species via chemical ligation

Maruyama Hideto, Matsuda Akira, Shuto Satoshi, Ito Yoshihiro, Abe Hiroshi

ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 247 巻 2014年3月

　前のページ - 次のページ　

<阿部 洋>

論文 - 阿部 洋

<阿部　洋>

論文 - 阿部　洋