2021/08/06 更新

写真a

チュウマン ヨシロウ
中馬 吉郎
CHUMAN Yoshiro
所属
教育研究院 自然科学系 数理物質科学系列 准教授
理学部 理学科 准教授
職名
准教授
外部リンク

学位

  • 博士(理学) ( 2001年3月   九州大学 )

研究キーワード

  • アプタマー

  • ペプチド

  • リン酸化

  • ホスファターゼ

  • 抗体

  • 抗癌剤

  • 生化学

  • バイオセンサー

  • バイオマテリアル

  • 生物化学

  • Functional biochemistry

  • Structural biochemistry

  • Biochemistry

研究分野

  • ナノテク・材料 / 生物分子化学

  • ナノテク・材料 / グリーンサステイナブルケミストリー、環境化学

  • ライフサイエンス / 腫瘍診断、治療学

  • ナノテク・材料 / 生体化学

  • ライフサイエンス / 機能生物化学

経歴(researchmap)

  • 新潟大学   理学部理学科(化学プログラム)   准教授

    2017年4月 - 現在

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  • 新潟大学   理学部化学科   准教授

    2013年11月 - 2017年3月

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  • 北海道大学   大学院理学研究院   助教

    2007年4月 - 2013年10月

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  • 北海道大学   大学院理学研究科   助手

    2001年11月 - 2007年3月

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  • 米国国立衛生研究所(NIH)国立ガン研究所(NCI)   visiting fellow

    2001年5月 - 2003年10月

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  • イタリア国立衛生研究所・分子薬理学研究室   科研費国際学術共同研究協力員

    1999年9月 - 1999年10月

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  • イタリア国立衛生研究所・分子薬理学研究室   科研費国際学術共同研究協力員

    1998年9月 - 1998年12月

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  • 日本学術振興会特別研究員(DC1)

    1998年4月 - 2001年3月

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  • Postdoctoral Fellowships of Japan Society for the Promotion of Science

    1998年 - 2001年

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  • イタリア国立衛生研究所・分子薬理学研究室   科研費国際学術共同研究協力員

    1997年9月 - 1997年10月

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▶ 全件表示

経歴

  • 新潟大学   理学部 理学科   准教授

    2017年4月 - 現在

  • 新潟大学   有機物質化学   准教授

    2013年11月 - 2017年3月

学歴

  • 九州大学   九州大学理学部化学科卒業 学士(理学)

    1996年3月

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  • 九州大学   大学院理学研究科化学専攻修士課程修了 修士(理学)

    1998年3月

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  • 九州大学   大学院理学府分子科学専攻   博士課程修了 博士(理学)

    2001年3月

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所属学協会

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委員歴

  • 新潟生化学懇話会   幹事  

    2019年 - 現在   

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    団体区分:学協会

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  • 文部科学省   専門調査員  

    2019年 - 現在   

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    団体区分:政府

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  • Bentham Science publishers   Bentham Ambassador  

    2019年 - 現在   

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    団体区分:学協会

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  • The Japanese peptide society   10th International Peptide Symposium International Program Committee  

    2018年   

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  • 日本化学会   関東支部新潟地域懇談会事務局  

    2017年 - 現在   

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  • 日本ホスファターゼ学会   世話人  

    2016年 - 現在   

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  • N-hybrid   世話人  

    2016年 - 現在   

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  • 日本ペプチド学会   PNJ編集委員・HP委員  

    2014年 - 現在   

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  • 日本ペプチド学会   第40回若手ペプチド夏の勉強会 代表世話人  

    2007年   

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留学歴

  • 米国国立衛生研究所(NIH)国立ガン研究所(NCI)   博士研究員

    2001年5月 - 2003年10月

  • イタリア国立衛生研究所・分子薬理学研究室   科研費国際学術共同研究協力員

    1999年9月 - 1999年10月

  • イタリア国立衛生研究所・分子薬理学研究室   科研費国際学術共同研究協力員

    1998年9月 - 1998年12月

  • イタリア国立衛生研究所・分子薬理学研究室   科研費国際学術共同研究協力員

    1997年9月 - 1997年10月

 

論文

  • Methods for Identification of Substrates/Inhibitors of FCP/SCP Type Protein Ser/Thr Phosphatases 招待

    Masataka Mizunuma, Atsushi Kaneko, Shunta Imai, Kazuhiro Furukawa, Yoshiro Chuman

    Processes   8 ( 12 )   1598 - 1598   2020年12月

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Protein phosphorylation is the most widespread type of post-translational modification and is properly controlled by protein kinases and phosphatases. Regarding the phosphorylation of serine (Ser) and threonine (Thr) residues, relatively few protein Ser/Thr phosphatases control the specific dephosphorylation of numerous substrates, in contrast with Ser/Thr kinases. Recently, protein Ser/Thr phosphatases were reported to have rigid substrate recognition and exert various biological functions. Therefore, identification of targeted proteins by individual protein Ser/Thr phosphatases is crucial to clarify their own biological functions. However, to date, information on the development of methods for identification of the substrates of protein Ser/Thr phosphatases remains scarce. In turn, substrate-trapping mutants are powerful tools to search the individual substrates of protein tyrosine (Tyr) phosphatases. This review focuses on the development of novel methods for the identification of Ser/Thr phosphatases, especially small C-terminal domain phosphatase 1 (Scp1), using peptide-displayed phage library with AlF4−/BeF3−, and discusses the identification of putative inhibitors.

    DOI: 10.3390/pr8121598

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  • Development of Specific Inhibitors for Oncogenic Phosphatase PPM1D by Using Ion-Responsive DNA Aptamer Library 査読

    Atsushi Kaneko, Miyuu Watari, Masataka Mizunuma, Hikaru Saito, Kazuhiro Furukawa, Yoshiro Chuman

    Catalysts   10 ( 10 )   1153 - 1153   2020年10月

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    (1) Background: Ser/Thr protein phosphatase PPM1D is an oncogenic protein. In normal cells, however, PPM1D plays essential roles in spermatogenesis and immune response. Hence, it is necessary to develop novel PPM1D inhibitors without side effects on normal cells. Stimuli-responsive molecules are suitable for the spatiotemporal regulation of inhibitory activity. (2) Methods: In this study, we designed an ion-responsive DNA aptamer library based on G-quadruplex DNA that can change its conformation and function in response to monovalent cations. (3) Results: Using this library, we identified the PPM1D specific inhibitor M1D-Q5F aptamer. The M1D-Q5F aptamer showed anti-cancer activity against breast cancer MCF7 cells. Interestingly, the induction of the structural change resulting in the formation of G-quadruplex upon stimulation by monovalent cations led to the enhancement of the inhibitory activity and binding affinity of M1D-Q5F. (4) Conclusions: These data suggest that the M1D-Q5F aptamer may act as a novel stimuli-responsive anti-cancer agent.

    DOI: 10.3390/catal10101153

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  • Identification of a Specific Inhibitor of Human Scp1 Phosphatase Using the Phosphorylation Mimic Phage Display Method 査読

    Yoshida, T, Yamazaki, K, Imai, S, Banno, A, Kaneko, A, Furukawa, K, Chuman, Y

    Catalysts   9 ( 10 )   842   2019年10月

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    担当区分:責任著者   記述言語:英語  

    DOI: 10.3390/catal9100842

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  • PPM1D enhances retinoic acid-induced differentiation in human embryonic carcinoma cell line 査読

    Ogasawara, S., Chuman, Y., Michiba, T., Kamada, R., Imagawa, T., Sakaguchi, K.

    J. Biochem.   165 ( 6 )   471 - 477   2019年

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  • Development of a substrate identification method for human Scp1 phosphatase using phosphorylation mimic phage display 査読

    Kodai Otsubo, Takashi Yoneda, Atsushi Kaneko, Seiya Yagi, Kazuhiro Furukawa, Yoshiro Chuman

    Protein and Peptide Letters   25 ( 1 )   76 - 83   2018年1月

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    担当区分:責任著者   記述言語:英語   出版者・発行元:Bentham Science Publishers B.V.  

    Background: Protein phosphorylation is strictly regulated by protein kinases and protein phosphatases, and disordered regulation of protein phosphorylation often causes serious diseases, such as cancer. Protein phosphatases are divided into two major groups: tyrosine (Tyr) phosphatases and serine/threonine (Ser/Thr) phosphatases. Substrate trapping mutants are frequently used to characterize Tyr phosphatases and identify their substrates
    however, a rapid and simple method to identify substrates for Ser/Thr phosphatases has yet to be developed. Recently it has reported that AlF4-/AlF3 and BeF3 - form a complex with Mg2+ in the catalytic center of FCP/SCP phosphatases, and that the Mg2+-AlF4 -/AlF3 complex mimics the transition state of the hydrolysis step, while the Mg2+-BeF3 - complex mimics the aspartylphosphate intermediate. Objectives: The main objective of this study was to develop a novel methodology, termed Phosphorylation Mimic Phage Display (PMPD), to identify substrates for Ser/Thr phosphatase Scp1 using peptide phage display libraries with Mg2+ and AlF4 -. Methods: Recombinant protein of human full-length Scp1 (rScp1) expressed in E. coli system was purified by Co2+ chelated affinity column, and then confirmed by SDS-PAGE and Western-blot analysis. The Ph.D.-C7C or M12 Phage Display Libraries (New England BioLabs, Beverly, MA) were screened using purified rScp1 immobilized on ELISA plate. Then, the plate was blocked with 0.5% (w/v) BSA in maleate buffer at 4°C for 3 h, before adding approximately 1×1010 plaque-forming units (pfu) of the phages in maleate blocking AlF4 - buffer to each well. After incubating, the wells were washed with maleate AlF4 - buffer to remove unbound phages. Then, phages were eluted with Mg2+ and AlF4 - free maleate buffer or with excess rScp1. After the third round of screening, the isolated phages were sequenced and subjected to binding analyses. Results: After panning by PMPD method, 46 and 60 clones were isolated from the Ph.D. C7C and Ph.D. 12 phage libraries, respectively, as Mg2+ or/and AlF4 - -dependent binding clones. The binding analyses showed that M12-1 and Dep-3 specifically bind to Scp1 in an AlF4 --dependent manner. Notably, the Dep-3 peptide contained a Thr-Pro-Met-Ser sequence, which is similar to the Ser2-Pro3-Thr4-Ser5 (Ser/Thr-Pro-partially hydrophobic residue-Ser) sequence found in CTD, which is an endogenous substrate for Scp1. Binding analyses also showed that both BP-14 and M12-6a bound to Scp1 in a Mg2+-dependent manner. BP-14 peptide contained Ser-Thr-Tyr and Pro-Phe-Glu sequences, which are similar to the Ser-Thr-Trp and Ile-Phe-Glu sequences found in M12-6a, suggesting that one or both of these tripeptides may be the binding motif(s) recognized by Scp1. Conclusion: We developed a substrate identification method for the Ser/Thr phosphatase Scp1 using a novel phage display method with AlF4 -. Dep-3 showed a core sequence similar to that of the CTD of RNA polymerase II, an endogenous Scp1 substrate, suggesting that this method is applicable for identifying novel Scp1 substrate candidates. This method will also be applicable for other FCP/SCP-type phosphatases, allowing us to better understand the substrate recognition mechanisms of Ser/Thr phosphatases.

    DOI: 10.2174/0929866525666171206114913

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  • Non-farnesylated B-type lamin can tether chromatin inside the nucleus and its chromatin interaction requires the Ig-fold region 査読

    Ryo Uchino, Shin Sugiyama, Motoi Katagiri, Yoshiro Chuman, Kazuhiro Furukawa

    CHROMOSOMA   126 ( 1 )   125 - 144   2017年2月

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

    Lamins are thought to direct heterochromatin to the nuclear lamina (NL); however, this function of lamin has not been clearly demonstrated in vivo. To address this, we analyzed (p)olytene chromosome morphology when artificial lamin variants were expressed in Drosophila endoreplicating cells. We found that the CaaX-motif-deleted B-type lamin Dm(0), but not A-type lamin C, was able to form a nuclear envelope-independent layer that was closely associated with chromatin. Other nuclear envelope proteins were not detected in this "ectopic lamina," and the associated chromatin showed a repressive histone modification maker but not a permissive histone modification marker nor RNA polymerase II proteins. Furthermore, deletion of the C-terminal lamin-Ig-fold domain prevents chromatin association with this ectopic lamina. Thus, non-farnesylated B-type lamin Dm(0) can form an ectopic lamina and induce changes to chromatin structure and status inside the interphase nucleus.

    DOI: 10.1007/s00412-016-0581-x

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  • PPM1D controls nucleolar formation by up-regulating phosphorylation of nucleophosmin 査読

    Yuuki Kozakai, Rui Kamada, Junya Furuta, Yuhei Kiyota, Yoshiro Chuman, Kazuyasu Sakaguchi

    SCIENTIFIC REPORTS   6   33272   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    An increase of nucleolar number and size has made nucleoli essential markers for cytology and tumour development. However, the underlying basis for their structural integrity and abundance remains unclear. Protein phosphatase PPM1D was found to be up-regulated in different carcinomas including breast cancers. Here, we demonstrate for the first time that PPM1D regulates nucleolar formation via inducing an increased phosphorylation of the nucleolar protein NPM. We show that PPM1D overexpression induces an increase in the nucleolar number regardless of p53 status. We also demonstrated that specific sequential phosphorylation of NPM is important for nucleolar formation and that PPM1D is a novel upstream regulator of this phosphorylation pathway. These results enhance our understanding of the molecular mechanisms that govern nucleoli formation by demonstrating that PPM1D regulates nucleolar formation by regulating NPM phosphorylation status through a novel signalling pathway, PPM1D-CDC25C-CDK1-PLK1.

    DOI: 10.1038/srep33272

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  • Patterning nanofibrils through the templated growth of multiple modified amyloid peptides 査読

    Hiroki Sakai, Ken Watanabe, Fuki Kudoh, Rui Kamada, Yoshiro Chuman, Kazuyasu Sakaguchi

    SCIENTIFIC REPORTS   6   31993   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    There has been considerable interest in the patterning of functionalized nanowires because of the potential applications of these materials to the construction of nanodevices. A variety of biomolecular building blocks containing amyloid peptides have been used to functionalize nanowires. However, the patterning of self-assembled nanowires can be challenging because of the difficulties associated with controlling the self-assembly of these functionalized building blocks. Herein, we present a versatile approach for the patterning of nanowires based on the combination of templated fibril growth with a versatile functionalization method using our structure-controllable amyloid peptides (SCAPs). Using this approach, we have succeeded in the formation of multi-type nanowires with tandem domain structures in high yields. Given that the mixing-SCAP method can lead to the formation of tandem fibrils, it is noteworthy that our method allowed us to control the initiation of fibril formation from the gold nanoparticles, which were attached to a short fibril as initiation points. This approach could be used to prepare a wide variety of fibril patterns, and therefore holds great potential for the development of novel self-assembled nanodevices.

    DOI: 10.1038/srep31993

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  • Effective Cellular Morphology Analysis for Differentiation Processes by a Fluorescent 1,3a,6a-Triazapentalene Derivative Probe in Live Cells 査読

    Rui Kamada, Fumi Tano, Fuki Kudoh, Nozomi Kimura, Yoshiro Chuman, Ayumi Osawa, Kosuke Namba, Keiji Tanino, Kazuyasu Sakaguchi

    PLOS ONE   11 ( 8 )   e0160625   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Nuclear and cytoplasmic morphological changes provide important information about cell differentiation processes, cell functions, and signal responses. There is a strong desire to develop a rapid and simple method for visualizing cytoplasmic and nuclear morphology. Here, we developed a novel and rapid method for probing cellular morphological changes of live cell differentiation process by a fluorescent probe, TAP-4PH, a 1,3a, 6a-triazapentalene derivative. TAP-4PH showed high fluorescence in cytoplasmic area, and visualized cytoplasmic and nuclear morphological changes of live cells during differentiation. We demonstrated that TAP-4PH visualized dendritic axon and spine formation in neuronal differentiation, and nuclear structural changes during neutrophilic differentiation. We also showed that the utility of TAP-4PH for visualization of cytoplasmic and nuclear morphologies of various type of live cells. Our visualizing method has no toxicity and no influence on the cellular differentiation and function. The cell morphology can be rapidly observed after addition of TAP-4PH and can continue to be observed in the presence of TAP-4PH in cell culture medium. Moreover, TAP-4PH can be easily removed after observation by washing for subsequent biological assay. Taken together, these results demonstrate that our visualization method is a powerful tool to probe differentiation processes before subsequent biological assay in live cells.

    DOI: 10.1371/journal.pone.0160625

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  • Novel inhibitors targeting PPM1D phosphatase potently suppress cancer cell proliferation 査読

    Sari Ogasawara, Yuhei Kiyota, Yoshiro Chuman, Ayano Kowata, Fumihiko Yoshimura, Keiji Tanino, Rui Kamada, Kazuyasu Sakaguchi

    BIOORGANIC & MEDICINAL CHEMISTRY   23 ( 19 )   6246 - 6249   2015年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Protein phosphatase magnesium-dependent 1 delta (PPM1D, Wip1) is a p53 inducible serine/threonine phosphatase. PPM1D is a promising target protein in cancer therapy since overexpression, missense mutations, truncating mutations, and gene amplification of PPM1D are reported in many tumors, including breast cancer and neuroblastoma. Herein, we report that a specific inhibitor, SL-176 that can be readily synthesized in 10 steps, significantly inhibits proliferation of a breast cancer cell line overexpressing PPM1D and induces G2/M arrest and apoptosis. SL-176 decreases PPM1D enzyme activity potently and specifically in vitro. These results demonstrate that SL-176 could be a useful lead compound in the development of effective anti-cancer agents. (C) 2015 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.bmc.2015.08.042

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  • Synthesis of yellow and red fluorescent 1,3a, 6a-triazapentalenes and the theoretical investigation of their optical properties 査読

    Kosuke Namba, Ayumi Osawa, Akira Nakayama, Akane Mera, Fumi Tano, Yoshiro Chuman, Eri Sakuda, Tetsuya Taketsugu, Kazuyasu Sakaguchi, Noboru Kitamura, Keiji Tanino

    CHEMICAL SCIENCE   6 ( 2 )   1083 - 1093   2015年

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    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  

    To expand the originally developed fluorescent 1,3a, 6a-triazapentalenes as fluorescent labelling reagents, the fluorescence wavelength of the 1,3a, 6a-triazapentalenes was extended to the red color region. Based on the noteworthy correlation of the fluorescence wavelength with the inductive effect of the 2-substituent, electron-deficient 2-(2-cyano-4-methoxycarbonylphenyl)-1,3a, 6a-triazapentalene and 2-(2,6-dicyano-4-methoxycarbonylphenyl)-1,3a, 6a-triazapentalene were synthesized. The former exhibited yellow fluorescence and the latter exhibited red fluorescence, and both compounds exhibited large Stokes shifts, and the 1,3a, 6a-triazapentalene system enabled the same fluorescent chromophore to cover the entire region of visible wavelengths. The potential applications of the 1,3a, 6a-triazapentalenes as fluorescent probes in the fields of the life sciences were investigated, and the 1,3a, 6a-triazapentalene system was clearly proven to be useful as a fluorescent reagent for live cell imaging. Quantum chemical calculations were performed to investigate the optical properties of the 1,3a, 6a-triazapentalenes. These calculations revealed that the excitation involves a significant charge-transfer from the 1,3a, 6a-triazapentalene skeleton to the 2-substituent. The calculated absorption and fluorescence wavelengths showed a good correlation with the experimental ones, and thus the system could enable the theoretical design of substituents with the desired optical properties.

    DOI: 10.1039/c4sc02780a

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  • Function of Proto-oncogene Product PPM1D and Development of PPM1D Inhibitors for Cancer Chemotherapy 査読

    Kamada R, Chuman Y, Kozakai Y, Sakaguchi K

    Seikagaku. The Journal of Japanese Biochemical Society   87 ( 5 )   531   2015年

  • Secreted Frizzled-Related Protein Potentiation versus Inhibition of Wnt3a/β-catenin Signaling. 査読

    Xaviera, C.P, Melikova, M, Chuman, Y, ren, A, Baljinnyam, B, Rubin, J.S

    Cell. Signal.   26 ( 1 )   94 - 101   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.cellsig.2013.09.016

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  • Formation of functionalized nanowires by control of self-assembly using multiple modified amyloid peptides 査読

    Hiroki Sakai, Ken Watanabe, Yuya Asanomi, Yumiko Kobayashi, Yoshiro Chuman, Lihong Shi, Takuya Masuda, Thomas Wyttenbach, Michael T. Bowers, Kohei Uosaki, Kazuyasu Sakaguchi

    Advanced Functional Materials   23 ( 39 )   4881 - 4887   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Amyloid peptides have great potential as building blocks in the creation of functional nanowires due to their natural ability to self-assemble into nanofibrillar structures and because they can be easily modified with various functional groups. However, significant modifications of an amyloid peptide generally alter its self-assembly property, making it difficult to construct functionalized fibrils with a desired structure and function. In this study, a very effective method to overcome this problem is demonstrated by using our structure-controllable amyloid peptides (SCAPs) terminated with a three-amino-acid-residue cap. The method consists on mixing two or more structurally related amyloid peptides with a fraction of modified SCAPs which co-assemble into a fibril. This SCAP-mixing method provides remarkable control over the self-assembly process both on the small oligomers level and the macroscopic fibrils level. Furthermore, it is shown that the modified peptides imbedded in the resulting fibril can subsequently be functionalized to generate nanowires with the desired properties, highlighting the importance of this SCAP method for nanotechnology applications. Copyright © 2013 WILEY-VCH Verlag GmbH &amp
    Co. KGaA, Weinheim.

    DOI: 10.1002/adfm.201300577

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  • Effects of E/Z Configuration of Fluoroalkene-containing HDAC Inhibitors on Selectivity for HDAC Isoforms 査読

    Yoshiro Chuman, Mariko Ueyama, Satoshi Sano, Fei Wu, Yuhei Kiyota, Takayoshi Higashi, Satoshi Osada, Kazuyasu Sakaguchi

    CHEMISTRY LETTERS   42 ( 8 )   833 - 835   2013年8月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CHEMICAL SOC JAPAN  

    Histone deacetylase (HDAC) inhibitors belong to a new class of potential anticancer agents. It may be possible to reduce some of the toxicity by specifically targeting only the HDAC isoform. Here, stereoisomeric HDAC inhibitors containing fluoroalkene were analyzed for their specificity toward HDAC isoforms. Z-Form 1(Z) showed high affinity to HDACs whereas E-isoform 1(E) had lower affinity to HDAC1 and HDAC4. These data suggested that introduction of alkene with E/Z configuration to HDAC inhibitor can be a new strategy to develop the isoform-selective HDAC inhibitors.

    DOI: 10.1246/cl.130243

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  • Inhibition of tumor suppressor protein p53-dependent transcription by a tetramerization domain peptide via hetero-oligomerization 査読

    Junya Wada, Rui Kamada, Toshiaki Imagawa, Yoshiro Chuman, Kazuyasu Sakaguchi

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   22 ( 8 )   2780 - 2783   2012年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Tumor suppressor protein p53 induces cell cycle arrest, apoptosis, and senescence in response to cellular stresses. The p53 tetramer formation is essential for its functions. Despite of these crucial functions of p53 for integrity of genome, activation of the p53 signal pathway causes low induced pluripotent stem (iPS) cell generation efficiency. In this study, we report transient inhibition of p53-dependent transcription using a p53 tetramerization domain peptide that contains cell penetrating and nuclear localization signals. The peptide was efficiently introduced into cells and inhibited p21 expression via hetero-tetramerization with endogenous p53 protein. This method can be applied towards safe and efficient iPS cell generation. (C) 2012 Elsevier Ltd. All rights reserved.

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  • A small molecule inhibitor of p53-inducible protein phosphatase PPM1D 査読

    Hiroaki Yagi, Yoshiro Chuman, Yuuki Kozakai, Toshiaki Imagawa, Yu Takahashi, Fumihiko Yoshimura, Keiji Tanino, Kazuyasu Sakaguchi

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   22 ( 1 )   729 - 732   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    PPM1D is a p53-inducible Ser/Thr protein phosphatase. PPM1D gene amplification and overexpression have been reported in a variety of human tumors, including breast cancer and neuroblastoma. Because the phosphatase activity of PPM1D is essential for its oncogenic role, PPM1D inhibitors should be viable anti-cancer agents. In our current study, we showed that SPI-001 was a potent and specific PPM1D inhibitor. SPI-001 inhibited PPM1D phosphatase activity in PPM1D-overexpressing human breast cancer cells and increased phosphorylation of p53. Furthermore, SPI-001 suppressed cell proliferation by inducing apoptosis. Our present study suggested that SPI-001 was a potential lead compound in developing anti-cancer drugs. (C) 2011 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.bmcl.2011.10.084

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  • Phosphatase assay for multi-phosphorylated substrates using phosphatase specific-motif antibody 査読

    Yoshiro Chuman, Kanako Iizuka, Takeshi Honda, Hitoshi Onoue, Yasuyuki Shimohigashi, Kazuyasu Sakaguchi

    JOURNAL OF BIOCHEMISTRY   150 ( 3 )   319 - 325   2011年9月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Protein phosphorylation plays central roles in a wide variety of signal transduction pathways and most phosphorylated proteins contain multi-phosphorylated sites. PPM1 type Ser/Thr protein phosphatase family is known to show rigid substrate specificity unlike other Ser/Thr phosphatase PPP family including PP1, PP2A and PP2B. PPM1 type phosphatases are reported to play important roles in growth regulation and in cellular stress signalling. In this study, we developed a phosphatase assay of PPM1D using phosphatase motif-specific antibody. PPM1D is a member of PPM1 type Ser/Thr phosphatase and known to dephosphorylate Ser(P)-Gln sequence. The gene amplification and overexpression of PPM1D were reported in many human cancers. We generated the monoclonal antibody specific for the Ser(P)-Gln sequence, named 3G9-H11. The specificity of this method using ELISA enables the convenient measurement of the dephosphorylation level of only PPM1D target residues of substrate peptides with multiple phosphorylated sites in the presence of multiple phosphatases. In addition, the antibody was applicable to immunoblotting assay for PPM1D function analysis. These results suggested that this method should be very useful for the PPM1D phosphatase assay, including high-throughput analysis and screening of specific inhibitors as anti-cancer drugs. The method using phosphatase motif-specific antibody can be applied to other PPM1 phosphatase family.

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  • Probing Phenylalanine Environments in Oligomeric Structures with Pentafluorophenylalanine and Cyclohexylalanine 査読

    Takao Nomura, Rui Kamada, Issaku Ito, Koichi Sakamoto, Yoshiro Chuman, Koichiro Ishimori, Yasuyuki Shimohigashi, Kazuyasu Sakaguchi

    BIOPOLYMERS   95 ( 6 )   410 - 419   2011年6月

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    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-BLACKWELL  

    Stabilization of protein structures and protein protein interactions are critical in the engineering of industrially useful enzymes and in the design of pharmaceutically valuable ligands. Hydrophobic interactions involving phenylalanine residues play crucial roles in protein stability and protein-protein/peptide interactions. To establish an effective method to explore the hydrophobic environments of phenylalanine residues, we present a strategy that uses pentafluorophenylalanine (F(5)Phe) and cyclohexylalanine (Cha). In this study, substitution of F(5)Phe or Cha for three Phe residues at positions 328, 338, and 341 in the tetramerization domain of the tumor suppressor protein p53 was performed. These residues are located at the interfaces of p53 p53 interactions and are important in the stabilization of the tetrameric structure. The stability of the p53 tetrameric structure did not change significantly when F(5)Phe-containing peptides at positions Phe328 or Phe338 were used. In contrast, the substitution of Cha for Phe341 in the hydrophobic core enhanced the stability of the tetrameric structure with a T(m) value of similar to 100 degrees C. Phe328 and Phe338 interact with each other through pi-interactions, whereas Phe341 is buried in the surrounding alkyl side-chains of the hydrophobic core of the p53 tetramerization domain. Furthermore, high pressure-assisted denaturation analysis indicated improvement in the occupancy of the hydrophobic core. Considerable stabilization of the p53 tetramer was achieved by filling the identified cavity in the hydrophobic core of the p.5.3 tetramer. The results indicate the status of the Phe residues, indicating that the "pair substitution" of Cha and F(5)Phe is highly suitable for probing the environments of Phe residues. (C) 2011 Wiley Periodicals, Inc. Biopolymers 95: 410-419, 2011.

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  • sFRP-1 binds via its netrin-related motif to the N-module of thrombospondin-1 and blocks thrombospondin-1 stimulation of MDA-MB-231 breast carcinoma cell adhesion and migration 査読

    Gema Martin-Manso, Maria J. Calzada, Yoshiro Chuman, John M. Sipes, Charles P. Xavier, Vladimir Wolf, Svetlana A. Kuznetsova, Jeffrey S. Rubin, David D. Roberts

    ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS   509 ( 2 )   147 - 156   2011年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Secreted frizzled-related protein (sFRP)-1 is a Wnt antagonist that inhibits breast carcinoma cell motility, whereas the secreted glycoprotein thrombospondin-1 stimulates adhesion and motility of the same cells. We examined whether thrombospondin-1 and sFRP-1 interact directly or indirectly to modulate cell behavior. Thrombospondin-1 bound sFRP-1 with an apparent K(d) = 48 nM and the related sFRP-2 with a K(d) = 95 nM. Thrombospondin-1 did not bind to the more distantly related sFRP-3. The association of thrombospondin-1 and sFRP-1 is primarily mediated by the amino-terminal N-module of thrombospondin-1 and the netrin domain of sFRP-1. sFRP-1 inhibited alpha 3 beta 1 integrin-mediated adhesion of MDA-MB-231 breast carcinoma cells to a surface coated with thrombospondin-1 or recombinant N-module, but not adhesion of the cells on immobilized fibronectin or type I collagen. sFRP-1 also inhibited thrombospondin-1-mediated migration of MDA-MB-231 and MDA-MB-468 breast carcinoma cells. Although sFRP-2 binds similarly to thrombospondin-1, it did not inhibit thrombospondin-1-stimulated adhesion. Thus, sFRP-1 binds to thrombospondin-1 and antagonizes stimulatory effects of thrombospondin-1 on breast carcinoma cell adhesion and motility. These results demonstrate that sFRP-1 can modulate breast cancer cell responses by interacting with thrombospondin-1 in addition to its known effects on Wnt signaling. Published by Elsevier Inc.

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  • Effective method for formation of functionalized nanowires using amyloid peptides 査読

    Sakai Hiroki, Watanabe Ken, Chuman Yoshiro, Uosaki Kohei, Sakaguchi Kazuyasu

    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY   241   2011年3月

  • Novel chemical inhibitors specific for p53-inducible protein phosphatase PPM1D 査読

    Yagi Hiroaki, Chuman Yoshiro, Yoshimura Fumihiko, Tanino Keiji, Sakaguchi Kazuyasu

    Abstracts of Papers of the American Chemical Society   241   2011年

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  • Enhancement of transcriptional activity of mutant p53 tumor suppressor protein through stabilization of tetramer formation by calix[6]arene derivatives 査読

    Rui Kamada, Wataru Yoshino, Takao Nomura, Yoshiro Chuman, Toshiaki Imagawa, Takanori Suzuki, Kazuyasu Sakaguchi

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   20 ( 15 )   4412 - 4415   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Li-Fraumeni syndrome, a hereditary disorder characterized by familial clusters of early-onset multiple tumors, is caused by mutation of the TP53 gene, which encodes the p53 tumor suppressor protein. Mutation of Arg337 to histidine in the tetramerization domain of p53 is most frequently observed in Li-Fraumeni syndrome. This mutation is reported to destabilize the tetrameric structure of p53. We designed and synthesized calix[6] arene derivatives, which have six imidazole or pyrazole groups at the upper rim. In this study, we report, for the first time, the enhancement of the in vivo transcriptional activity of the most common Li-Fraumeni p53 mutant by imidazole-calix[6] arene through stabilization of the oligomer formation. (C) 2010 Elsevier Ltd. All rights reserved.

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  • Drastic Effects on Fibril Formation of Amyloid-beta Peptides by the Addition of Amino Acid Residue Units to the Termini 査読

    Yuya Asanomi, Yumiko Kobayashi, Hiroki Sakai, Takuya Masuda, Xinjiang Chen, Yoshiro Chuman, Kohei Uosaki, Kazuyasu Sakaguchi

    PROTEIN AND PEPTIDE LETTERS   17 ( 4 )   458 - 463   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    We report that the addition of amino acids to the amyloid peptide dramatically affected the structure and the rate of formation of amyloid fibrils. The attachment of three lysines to A beta(10-35) gave the formation of remarkably long fibrils, while three glutamates resulted in a faster formation rate of the fibrils.

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  • Fluoroalkene modification of mercaptoacetamide-based histone deacetylase inhibitors 査読

    Satoshi Osada, Satoshi Sano, Mariko Ueyama, Yoshiro Chuman, Hiroaki Kodama, Kazuyasu Sakaguchi

    BIOORGANIC & MEDICINAL CHEMISTRY   18 ( 2 )   605 - 611   2010年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. The mercaptoacetoamide-based inhibitors are reported to be less toxic than hydroxamate and are worthy of further consideration. Therefore, we have designed a series of analogs as potential inhibitors of HDACs, in which the mercaptoacetamide group was replaced by (mercaptomethyl) fluoroalkene, and their HDAC inhibitory activity was evaluated. Subnanomolar inhibition was observed for all synthetic compounds. (C) 2009 Elsevier Ltd. All rights reserved.

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  • Oxidation of Methionine Residue at Hydrophobic Core Destabilizes p53 Tetrameric Structure 査読

    Takao Nomura, Rui Kamada, Issaku Ito, Yoshiro Chuman, Yasuyuki Shimohigashi, Kazuyasu Sakaguchi

    BIOPOLYMERS   91 ( 1 )   78 - 84   2009年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOHN WILEY & SONS INC  

    The tumor suppressor protein p53 is a tetrameric phosphoprotein that. induces cell cycle, development, and differentiation by regulating the expression of target genes. The tetramerization of p53 is essential for its tumor suppressor functions. It has been known that oxidation of proteins affects their structure and function. A methionine residue (Met340) is located at the hydrophobic core tit p53 tetramerization domain. Here, we demonstrated that Met340 residue can be oxidized to methionine sulfoxide under oxidative conditions and investigated effects of-the oxidation of p53 tetramerization domain oil its stability and oligomerization state by CD measurement and gel filtration. The oxidation of Met340 drastically induced destabilization of the p53 tetramer by 22.8 kJ/mol of Delta Delta G (TM), while retaining the identical conformation as that of the wild-type peptide. Trypsin digestion experiments also showed that oxidation of Met340 allowed the peptide to form locally loose structure and become more sensitive to enzyme degradation. Tit(tetrameric structure may be destabilized because the oxidation of Met340 induces charge repulsion and/or steric hindrance between the sulfoxide groups. These results taken together suggested that oxidation of methionine residues tit the p53 protein might lie one of the inactivation mechanism of p53 transcriptional function under conditions of oxidative stress. (C) 2008 Periodicals, Inc. Biopolymers 91: 78-84, 2009.

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  • PPM1D430, a Novel Alternative Splicing Variant of the Human PPM1D, can Dephosphorylate p53 and Exhibits Specific Tissue Expression 査読

    Yoshiro Chuman, Wataru Kurihashi, Yohei Mizukami, Takehiro Nashimoto, Hiroaki Yagi, Kazuyasu Sakaguchi

    JOURNAL OF BIOCHEMISTRY   145 ( 1 )   1 - 12   2009年1月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    PPM1D is a PPM1 type protein phosphatase and is induced in response to DNA damage. PPM1D-deficient mice show defects in spermatogenesis and lymphoid cell functions but the mechanisms underlying these phenotypes remain unknown. In our current study, we identify and characterize an alternative splicing variant (denoted PPM1D430) of human PPM1D at both the mRNA and protein level. PPM1D430 comprises the common 420 residues of the known PPM1D protein (PPM1D605) and contains a stretch of PPM1D430-specific 10 amino acids. Semi-quantitative reverse transcriptionpolymerase chain reaction (RTPCR) analysis revealed that PPM1D430 mRNA is also induced in response to the genotoxic stress in a p53-dependent manner. In vitro phosphatase analysis and PPM1D430-specific RNA interference analysis further indicated that PPM1D430 can dephosphorylate Ser15 of human p53 both in vitro and in vivo. On the other hand, expression profiling of this gene by RTPCR analysis of a human tissue cDNA panel revealed that PPM1D430 is expressed exclusively in testes and in leucocytes whereas PPM1D605 is ubiquitous. In addition, PPM1D430 shows a different subcellular localization pattern and protein stability when compared with PPM1D605 under some conditions. Our current findings thus suggest that PPM1D430 may exert specific functions in immune response and/or spermatogenesis.

    DOI: 10.1093/jb/mvn135

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  • Effects of tumor-associated mutations in the p53 tetramerization domain on oligomerization state and transcriptional activity. 査読

    Kamada, R, Terai, T, Nomura, T, Chuman, Y, Imagawa, T, Sakaguchi, K

    Adv. Exp. Med. Biol.   611   567 - 568   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/978-0-387-73657-0_249

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  • Characterization of the active site and a unique uncompetitive inhibitor of the PPM1-type protein phosphatase PPM1D 査読

    Yoshiro Chuman, Hiroaki Yagi, Tomohiko Fukuda, Takao Nomura, Miho Matsukizono, Yasuyuki Shimohigashi, Kazuyasu Sakaguchi

    PROTEIN AND PEPTIDE LETTERS   15 ( 9 )   938 - 948   2008年9月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    Protein phosphatase magnesium-dependent 1, delta (PPM1D) is a member of the PPM1 (formerly PP2C) protein phosphatase family, and is induced in response to DNA damage. The overexpression of PPM1D is thought to exert oncogenic effects through the inhibition of tumor suppressor proteins. PPM1D shows high selectivity for the primary sequence in its substrates when compared with other phosphatases, but the mechanisms underlying substrate recognition by this enzyme is not clearly known. In our present study we wished to identify the active center and further elucidate the substrate preference of PPM1D, and to this end performed sequence alignments among the human PPM1 type phosphatases. The results of this analysis clearly showed that the putative active site residues of PPM1D are highly conserved among the PPM1 family members. Phosphatase analyses using PPM1D mutants further identified the metal-chelating residues and a phosphate binding residue. In kinetic analyses using a series of phosphorylated p53 peptide analogs, the introduction of acidic residues into the region flanking the sites of dephosphorylation enhanced their affinity with PPM1D. Homology modeling of PPM1D also revealed that PPM1D contains two characteristic loops, a Pro-residue rich loop on the opposite side of the active site and a basic-residue rich loop in the vicinity of the active site in the catalytic domain. Interestingly, nonhydrolyzable AP4-3E peptides derived from the acidic p53 peptide analogs very effectively blocked PPM1D activity in an uncompetitive manner, suggesting that AP4-3E peptides may be useful lead compounds in the development of novel inhibitors of PPM1D.

    DOI: 10.2174/092986608785849236

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  • Differential recognition of phosphorylated transactivation domains of p53 by different p300 domains 査読

    Smarajit Polley, Soumi Guha, Neeladri Sekhar Roy, Sanchari Kar, Kazuyasu Sakaguchi, Yoshiro Chuman, V. Swaminathan, Tapas Kundu, Siddhartha Roy

    JOURNAL OF MOLECULAR BIOLOGY   376 ( 1 )   8 - 12   2008年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

    Histone acetyltransferases form crucial links in transducing extrinsic signals to actual initiation of transcription. A multitude of stress signal integrations occur through the interaction of p300 with p53 phosphorylated at different residues of the transactivation domain. How such interactions activate different gene expression programs remains largely unknown. p300 contains at least five domains that are known to interact with p53, but their role in transcription regulation is not known. We measured the binding affinity of various phosphorylated transactivation. domains towards several p53 binding domains of p300 by fluorescence anisotropy. The binding affinities of different phosphorylated transactivation domains of p53 towards different domains of p300 vary by several orders of magnitude, indicating that interactions of different post-translationally modified forms of p53 may occur through different domains of p300. Thus, different post-translationally modified p53 fragments may form transcription-initiating complexes of different configurations, leading to the activation of different promoters and pathways. (C) 2007 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.jmb.2007.11.082

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  • Differential receptor binding characteristics of consecutive phenylalanines in mu-opioid specific peptide ligand endomorphin-2 査読

    Takeshi Honda, Naoto Shirasu, Kaname Isozaki, Michiaki Kawano, Daiki Shigehiro, Yoshiro Chuman, Tsugumi Fujita, Takeru Nose, Yasuyuki Shimohigashi

    BIOORGANIC & MEDICINAL CHEMISTRY   15 ( 11 )   3883 - 3888   2007年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Endogenous opioid peptides consist of a conserved amino acid residue of Phe 3 and Phe 4, although their binding modes for opioid receptors have not been elucidated in detail. Endomorphin-2, which is highly selective and specific for the mu opioid receptor, possesses two Phe residues at the consecutive positions 3 and 4. In order to clarify the role of Phe 3 and Phe 4 in binding to the It receptor, we synthesized a series of analogs in which Phe 3 and Phe 4 were replaced by various amino acids. It was found that the aromaticity of the Phe-p-phenyl groups of Phe 3 and Phe 4 is a principal determinant of how strongly it binds to the receptor, although better molecular hydrophobicity reinforces the activity. The receptor binding subsites of Phe 3 and Phe 4 of endomorphin-2 were found to exhibit different structural requirements. The results suggest that [Trp 3]endomorphin-2 (native endomorphin-1) and endomorphin-2 bind to different receptor subclasses. (C) 2007 Elsevier Ltd. All rights reserved.

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  • Function of Basic Loop in Substrate Recognition of Protein Phosphatase PPM1D. 査読

    Chuman, Y, Fukuda, T, Yagi, H, Sakaguchi, K

    Peptide Sci.   2006   17 - 18   2007年

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  • Structural isoforms of the circadian neuropeptide PDF expressed in the optic lobes of the cricket Gryllus bimaculatus: Immunocytochemical evidence from specific monoclonal antibodies 査読

    Takeshi Honda, Ayami Matsushima, Kazunori Sumida, Yoshiro Chuman, Kazuyasu Sakaguchi, Hitoshi Onoue, Ian A. Meinertzhagen, Yasuyuki Shimohigashi, Miki Shimohigashi

    JOURNAL OF COMPARATIVE NEUROLOGY   499 ( 3 )   404 - 421   2006年11月

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    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-LISS  

    Pigment-dispersing factor (PDF) is an 18-mer peptide that acts as a principal neurotransmitter of the insect circadian clock. Our previous study, utilizing anti-Uca beta-PDH polyclonal antibody (pAb) to immunolabel the optic lobe of the cricket Gryllus bimaculatus, suggested the existence of an alternative PDF-like peptide in the outer cells of the first neuropile, or lamina (La), which were much less immunoreactive than the inner cells of the second neuropile, the medulla (Me). To obtain structural information about such a PDF-like peptide, we prepared 10 anti-Gryllus PDF monoclonal (mAb) and pAb antibodies and analyzed their detailed epitope specificities. The PDFMe and PDFLa inner cells and their axonal projections were clearly immunoreactive to all these antibodies, revealing the widespread immunocytochemical organization of the PDF system in the optic lobe, as seen previously with anti-Uca beta-PDH pAb and anti-Gryllus PDF mAb, the epitope structures of which were also clarified in this study. The lamina outer cells, which we found lacked a target pdf mRNA, displayed specific immunoreactivities, indicating that the cells contain a distinct PDF-like peptide possessing both N- and C-terminal structures. These cells were not immunolabeled by some other monoclonal antibodies, however, implying that the PDFLa outer cells have a PDF isoform peptide devoid of Asn at positions 6 and 16. This isoform was also identified in a varicose arborization in the lamina. These results suggest not only the structure of the peptide, but also the possibility of additional functions of this novel PDF isoform.

    DOI: 10.1002/cne.21112

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  • Different structural requirements for the constitutive and the agonist-induced activities of the beta(2)-adrenergic receptor 査読

    C Ambrosio, P Molinari, F Fanelli, Y Chuman, M Sbraccia, O Ugur, T Costa

    JOURNAL OF BIOLOGICAL CHEMISTRY   280 ( 25 )   23464 - 23474   2005年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    We converted Ser-207, located in helix 5 of the beta(2)-adrenergic receptor, into all other natural amino acids. To quantify receptor activation as a receptor number-independent parameter and directly related to G(s) activation, we expressed the mutants in a G alpha(s)-tethered form. GTP exchange in such constructs is restricted to the fused alpha-subunit and is a linear function of the receptor concentration. Except S207R, all other mutants were expressed to a suitable level for investigation. All mutations reduced the binding affinities of the catechol agonists, epinephrine and isoproterenol, and the extent of reduction was unrelated to the residue ability to form hydrogen bonds. Instead, both enhancements and reductions of affinity were observed for the partial agonist halostachin and the antagonist pindolol. The mutations also enhanced and diminished ligand-induced receptor activation, but the effects were strictly ligand-specific. Polar residues such as Asp and His exalted the activation by full agonists but suppressed that induced by the partial agonists halostachin and dichloroisoproterenol. In contrast, hydrophobic residues such as Ile and Val augmented partial agonist activation. Only Ile and Lys produced a significant increase of constitutive activity. The effects on binding and activity were not correlated, nor did such parameters show any clear correlation with up to 78 descriptors of amino acid physicochemical properties. Our data question the idea that Ser-207 is exposed to the polar crevice in the unbound receptor. They also suggest that the active receptor form induced by a full agonist might be substantially different from that caused by constitutive activation.

    DOI: 10.1074/jbc.M502901200

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  • Mechanism of Amyloid-Like Fibrillar Aggregation of Mutant Peptide of p53 Tetramerization Domain

    ASANOMI Yuya, TAKAKUSAGI Satoru, CHUMAN Yoshiro, KAYA Shunji, IMAGAWA Toshiaki, UOSAKI Kohei, SAKAGUCHI Kazuyasu

    Peptide science : proceedings of the ... Japanese Peptide Symposium   2004 ( 0 )   313 - 316   2005年3月

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

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  • Molecular Cloning and Circadian Expression Profile of Pacemaker Neuropeptide PDF in Diptera

    Matsushima, S, Yokotani, S, Sato, S, Kaneki, A, Takeda, Y, Chuman, Y, Ozaki, M, Asai, D, Nose, T, Onoue, H, Ito, Y, Tominaga, Y, Shimohigashi, Y, Shimohigashi, M

    Lett., Peptide Sci.   2005年

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  • Identification of a peptide binding motif for secreted frizzled-related protein-1 査読

    Y Chuman, A Uren, J Cahill, C Regan, Wolf, V, BK Kay, JS Rubin

    PEPTIDES   25 ( 11 )   1831 - 1838   2004年11月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Secreted Frizzled-related proteins (sFRPs) bind Wnts and modulate their activity. To identify putative sFRP-1 binding motifs, we screened an M 13 phage displayed combinatorial peptide library. A predominant motif, LN-VDGRW-L/V, was present in similar to70% of the phage that bound sFRP-1. Use of peptide/alkaline phosphatase chimeras and alanine scanning confirmed that the conserved motif was important for sFRP-1 recognition. The dissociation constant for a peptide/sFRP-1 complex was 3.9 muM. Additional analysis revealed that DGR was the core of the binding motif. Although Wnt proteins lack this sequence, other proteins possessing the DGR motif may function as novel binding partners for sFRP-1. Published by Elsevier Inc.

    DOI: 10.1016/j.peptides.2004.07.010

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  • Secreted frizzled-related protein-1 inhibits RANKL-dependent osteoclast formation 査読

    KD Hausler, NJ Horwood, Y Chuman, JL Fisher, J Ellis, TJ Martin, JS Rubin, MT Gillespie

    JOURNAL OF BONE AND MINERAL RESEARCH   19 ( 11 )   1873 - 1881   2004年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BONE & MINERAL RES  

    We determined that sFRP-1 mRNA was differentially expressed by osteoblast/stromal cell lines and that sFRP-1 neutralizing antibodies and siRNA complementary to sFRP-1 coding sequence enhanced, while recombinant sFRP-1 inhibited, osteoclast formation. In studying the mechanism of action for sFRP-1, we found that sFRP-1 could bind recombinant RANKL. These results suggest potential cross-talk between Wnt and RANKL pathways.

    DOI: 10.1359/JBMR.040807

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  • Structural analysis and identification of novel isoforms of the circadian clock gene period in the silk moth Bombyx mori 査読

    Y Takeda, Y Chuman, N Shirasu, S Sato, A Matsushima, A Kaneki, Y Tominaga, Y Shimohigashi, M Shimohigashi

    ZOOLOGICAL SCIENCE   21 ( 9 )   903 - 915   2004年9月

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

    The molecular basis of the circadian clock is an autoregulatory feedback loop in which the PAS domain-containing protein PERIOD periodically inhibits its own transcription. In the present study on PERIOD of the silk moth Bombyx mori, we have cloned two distinct period mRNA homologues with different PAS domain sequences either with or without the pentapeptide GTQEK. A period cDNA fragment first amplified by PCR exhibited a 15 bp-deleted nucleotide sequence in the PAS domain, compared with the database sequence. A possible alternative splicing mechanism was examined by PCR analyses, and a 15 bp-inserted clone was also amplified. The entire sequences of these period a and period P isoforms were then determined by the 3' and 5' RACE methods. Isoform period a consists of a 3,324 bp oligonucleotide encoding 1,108 amino acid residues, whereas isoform period P comprises 3,309 bp corresponding to 1,103 amino acids. Isoforms period a and period P were found to be exactly identical except for the 15 bp deletion/insertion site. Such a pair of isoforms with a deletion/insertion sequence, namely two splice variants, has previously been reported only for the PERIOD proteins of the two honeybees, Apis mellifera and A. cerana. The occurrence of an alternative splicing mechanism in the a mori period gene was hypothesized based on the genome structure recently clarified. Bombyx mori PERIOD a and P proteins are the isomers that reveal firstly the different PAS domain sequences.

    DOI: 10.2108/zsj.21.903

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  • cDNA cloning of the housefly pigment-dispersing factor (PDF) precursor protein and its peptide comparison among the insect circadian neuropeptides 査読

    A Matsushima, S Sato, Y Chuman, Y Takedo, S Yokotani, T Nose, Y Tominaga, M Shimohigashi, Y Shimohigashi

    JOURNAL OF PEPTIDE SCIENCE   10 ( 2 )   82 - 91   2004年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOHN WILEY & SONS LTD  

    Pigment-dispersing factor (PDF), an 18-amino acid neuropeptide, is a principal circadian neurotransmitter for the circadian rhythms of the locomotor activity in flies. Recently, two completely different types of PDF precursor were clarified; that of the cricket Gryllus bimaculatus and that of the last-summer cicada Meimuna opalifera. The G. bimaculatus PDF precursor is extraordinarily short and comprises a nuclear localization signal (NLS), while the M. opalifera PDF precursor is of ordinary length, comparable to that seen for the precursors of crustacean beta-PDH homologues. Although their PDF peptide regions were exactly the same, the regions containing a signal peptide combined with a PDF-associated peptide (PAP) were remarkably different from each other. Such a grouping suggested a fundamental role for the PAP peptide in the circadian clock, perhaps associated with PDF function. In the present study, the cDNA cloning of PDF from the adult brains of the housefly Musca domestica was carried out and it was found that an isolated clone (527 bp) encodes a PDF precursor protein of ordinary length. The PDF peptide shows a high sequence identity (78%-94%) and similarity (89%-100%) to insect PDFs and also to the crustacean beta-PDH peptides. In particular, there is only a single amino acid difference between the PDFs of Musca and Drosophila; at position 14 Ser for Musca PDF and Asn for Drosophila PDF. A characteristic Ser(10) in Drosophila was retained in Musca, indicating the presence of a structural profile unique to these PDFs. The results of sequence analyses suggest that Musca and Drosophila PDFs are to be considered members of a single group that has evolved structurally. When the primary structure of the PAP regions was compared, the Musca PDF precursor also belonged to the same group as that to which the Drosophila PDF precursor belongs. Copyright (C) 2003 European Peptide Society and John Wiley Sons, Ltd.

    DOI: 10.1002/psc.511

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  • Molecular cloning and circadian expression profile of insect neuropeptide PDF in black blowfly, Phormia regina. 査読

    Matsushima, A, Yokotani, S, Liu, X, Sumida, K, Honda, T, Sato, S, Kaneki, A, Takeda, Y, Chuman, Y, Ozaki, M, Asai, D, Nose, T, Onoue, H, Ito, Y, Tominaga, Y, Shimohigashi, Y, Shimohigashi, M

    Lett. Peptide Sci.   10   419 - 430   2003年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/BF02442573

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  • A circadian neuropeptide, pigment-dispersing Factor-PDF, in the last-summer cicada Meimuna opalifera: cDNA cloning and immunocytochemistry 査読

    S Sato, Y Chuman, A Matsushima, Y Tominaga, Y Shimohigashi, M Shimohigashi

    ZOOLOGICAL SCIENCE   19 ( 8 )   821 - 828   2002年8月

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

    Pigment-dispersing factor (PDF), an 18-amino acid neuropeptide, is a principal circadian neuromodulator functioning downstream of the insect brain's circadian.clock, modulating daily rhythms of locomotor activity. Recently, we found that PDF precursors of the cricket Gryllus bimaculatus comprise a nuclear localization signal (NLS). Moreover, the nuclear localization of PDF immunoreactivity and the translocation of GFP-fused PDF precursor into the nucleus have both been demonstrated. These suggest a fundamental role for PDF peptide in the circadian clock system within the nucleus, in addition to its role in downstream neural events. In the present study, we carried out the cDNA cloning of PDF from adult brains of the last-summer cicada Meimuna opalifera, and found that an isolated clone (545 bp) encodes an ordinary PDF precursor protein. PDF peptide itself shows a high sequence identity (78-94%) and similarity (89-100%) to insect PDFs and also to the crustacean beta-PDH peptides. The computer-assisted sequence analysis of PDF precursor revealed a possible translocation into the nucleus, despite the lack of a definite NLS-like sequence. Using immunocytochemistry, the optic lobes of M. opalifera revealed PDF-immunoreactive neurons in both the medulla and lamina neuropiles. All these PDF cells exhibited prominent immunolabeling of both their perikarya and axons, but not their nuclei. Our results provide the first structural and immunocytochemical identification of PDF neurons in Hemiptera.

    DOI: 10.2108/zsj.19.821

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  • cDNA cloning and nuclear localization of the cireadian neuropeptide designated as pigment-dispersing factor PDF in the cricket Gryllus bimaculatus 査読

    Y Chuman, A Matsushima, S Sato, K Tomioka, Y Tominaga, IA Meinertzhagen, Y Shimohigashi, M Shimohigashi

    JOURNAL OF BIOCHEMISTRY   131 ( 6 )   895 - 903   2002年6月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPANESE BIOCHEMICAL SOC  

    Pigment-dispersing factor (PDF) was recently reported to be a principal circadian neuromodulator involved in transmitting circadian rhythms of daily locomotion in insects. In Drosophila, PDF functions in some of the neurons expressing the clock genes period, timeless, Clock, and cycle, and those clock genes in turn regulate pdf gene expression. In the present study, we cloned a cDNA encoding PDF in the brain of a nocturnal insect, the cricket Gryllus bimaculatus, and found that an isolated clone (310 bp) codes for an extraordinarily short precursor protein with no definite signal sequence, but a nuclear localization signal (NLS)-like sequence instead. The cricket PDF exhibits high sequence identity (78-94%) and similarity (89-100%) to insect PDFs and also to crustacean beta-PDH peptides. In the optic lobes of G. bimaculatus there are PDF-immunoreactive neurons in both the medulla and lamina neuropiles. Among the strongly immunoreactive lamina PDF neurons, on electron microscopy we identified cells exhibiting distinct staining that is not only cytoplasmic but also nuclear. When GFP-fused PDF precursor proteins were expressed in COS-7 cells, distinct translocation of the fusion protein into the nucleus was observed. This is the first finding of PDF peptide in the nucleus, which suggests a fundamental role of PDF peptide per se in the circadian clock system.

    DOI: 10.1093/oxfordjournals.jbchem.a003180

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  • The role of deltorphin II phenylalanine reside in binding to the delta opioid receptor 査読

    T Honda, N Shirasu, Y Chuman, K Okada, T Fujita, T Nose, Y Shimohigashi

    BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN   73 ( 11 )   2549 - 2552   2000年11月

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

    Deltorphin II is a peptide ligand specific for the delta opioid receptor. In order to elucidate the role of Phe(3) in binding to the delta opioid receptor, we synthesized a series of analogs in which Phe(3) was replaced by various amino acids such as Ala, cyclohexylalanine (Cha), fluorophenylalanines, and other alkyl-side chain amino acids (Val, Leu, and norleucine (Nle)). It was found that [Cha(3)]deltorphin II and [Nle(3)]deltorphin II retain almost a full receptor binding affinity. The results indicated that the Phe(3)-phenyl group of deltorphin II can be substituted by the alkyl groups such as cyclohexyl and propyl in the interaction with the delta receptor.

    DOI: 10.1246/bcsj.73.2549

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  • Highly potent nociceptin analog containing the Arg-Lys triple repeat 査読

    K Okada, T Sujaku, Y Chuman, R Nakashima, T Nose, T Costa, Y Yamada, M Yokoyama, A Nagahisa, Y Shimohigashi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   278 ( 2 )   493 - 498   2000年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC  

    One of the structural characteristics of a neuropeptide nociceptin is the existence of Arg-Lys (RK) residues at positions 8-9 and 12-13; both RKs have been suggested to bind to the acidic amino acid cluster in the second extracellular loop of the seven transmembrane domain receptor ORL1. With a design strategy of attempting to obtain an analog that binds moire strongly to the receptor's acidic cluster, we synthesized a series of nociceptin analogs in which the RK dipeptide unit was placed at positions 6-7, 10-11, or 14-15 adjacent to the parent RKs. Among these nociceptin analogs containing the RK triple repeat, [Arg-Lys(6-7)]. and [Arg-Lys(10-11)]nociceptins exhibited weak activities (6-9 and 60-90% of nociceptin, respectively) both in the receptor binding assay and in the [S-35]GTP gammaS binding functional assay. In contrast, [Arg-Lys(14-15)]nociceptin was found to be very potent in both assays (3-fold in binding and 17-fold in GTP gammaS functional assay). [Arg-Lys(14-15)]nociceptin was the first peptide analog found to be stronger than the parent nociceptin, and structure-activity studies have suggested that the incorporated Arg-Lys(14-15) interacts with either the receptor acidic amino acid cluster or the receptor aromatic aminoacidresidues. (C) 2000 Academic Press.

    DOI: 10.1006/bbrc.2000.3822

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  • Regional and accelerated molecular evolution in group I snake venom gland phospholipase A(2) isozymes 査読

    Y Chuman, Nobuhisa, I, T Ogawa, M Deshimaru, T Chijiwa, NH Tan, Y Fukumaki, Y Shimohigashi, F Ducancel, JC Boulain, A Menez, M Ohno

    TOXICON   38 ( 3 )   449 - 462   2000年3月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    In accordance with detection of a few phospholipase A(2) (PLA(2)) isozyme genes by Southern blot analysis, only two cDNAs, named NnkPLA-I and NnkPLA-II, encoding group I PLA(2)s, NnkPLA-I and NnkPLA-II, respectively, were isolated from the venom gland cDNA library of Elapinae Naja naja kaouthia of Malaysia. NnkPLA-I and NnkPLA-II showed four amino acid substitutions, all of which were brought about by single nucleotide substitution. No existence of clones encoding CM-II and CM-III, PLA(2) isozymes which had been isolated from the venom of N. naja kaouthia of Thailand, in Malaysian N. naja kaouthia venom gland cDNA library was verified by dot blot hybridization analysis with particular probes. NnkPLA-I and NnkPLA-II differed from CM-II and CM-III with four and two amino acid substitutions. respectively, suggesting that their molecular evolution is regional. The comparison of NnkPLA-I, NnkPLA-II and cDNAs encoding other group I snake venom gland PLA(2)s indicated that the 5'- and 3'-untranslated regions are more conserved than the mature protein-coding region and that the number of nucleotide substitutions per nonsynonymous site is almost equal to that per synonymous sire in the protein-coding region, suggesting that accelerated evolution has occurred in group I venom gland PLA(2)s possibly to acquire new physiological functions. (C) 1999 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0041-0101(99)00165-8

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  • Exploration of universal cysteines in the binding sites of three opioid receptor subtypes by disulfide-bonding affinity labeling with chemically activated thiol-containing dynorphin A analogs

    Naoto Shirasu, Takuya Kuromizu, Hidenori Nakao, Yoshiro Chuman, Takeru Nose, Tommaso Costa, Yasuyuki Shimohigashi

    Journal of Biochemistry   126   254 - 259   1999年1月

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    A ligand containing an SNpys group, i.e. 3-nitro-2-pyridinesulfenyl linked to a mercapto (or thiol) group, can bind covalently to a free mercapto group to form a disulfide bond via the thiol-disulfide exchange reaction. This SNpys chemistry has been successfully applied to the discriminative affinity labeling of μ and δ opioid receptors with SNpys-containing enkephalins. In order to explore the mercapto groups conserved at or near the ligand binding sites of three opioid receptor subtypes, we synthesized two Cys(Npys)-containing analogs of dynorphin A, namely, [D-Ala2,Cys(Npys)8] dynorphin A-(1-9) amide (1) and Co-Ala2,Cys(Npys)12] dynorphin A-(1-13) amide (2). When rat (μ and δ) or guinea pig (χ) brain membranes were incubated with these Cys(Npys)-containing dynorphin A analogs and then assayed for inhibition of the binding of DAGO (μ), deltorphin II (δ), and U-69593 (χ), the number of receptors decreased sharply, depending upon the concentrations of these Cys(Npys)- containing dynorphin A analogs. It was found that dynorphin A analogs 1 and 2 effectively label μ receptors (EC50= 27-33 nM), but also label δ receptors fairly well (160-180 nM). However, for χ receptors they showed drastically different potencies as to affinity labeling; i.e., EC50= 210 nM for analog 1, but 10,000 nM for analog 2. Analog 2 labeled χ receptors about 50 times more weakly than analog 1. These results suggested that dynorphin A analog 1 labels the Cys residues conserved in μ, δ, and χ receptors, whereas analog 2 only labels the Cys residues conserved in μ, and δ receptors.

    DOI: 10.1093/oxfordjournals.jbchem.a022430

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  • A novel type of rat brain delta opioid receptors differenciated by cyclopropylphenyl alanine-containing enkephalin analog 査読

    Y Chuman, T Yasunaga, T Costa, Y Shimohigashi

    PEPTIDE SCIENCE - PRESENT AND FUTURE   207 - 209   1999年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:SPRINGER  

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  • Exploration of universal cysteines in the binding sites of three opioid receptor subtypes by disulfide-bonding affinity labeling with chemically activated thiol-containing dynorphin A analogs. 査読

    Shirasu, N, Kuromizu. T, Nakao, H, Chuman, Y, Nose, T, Costa, T, Shimohigashi, Y

    J. Biochem.   126   254 - 259   1999年

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  • Retrotransposable CR1-like elements in crotalinae snake genomes 査読

    Nobuhisa, I, T Ogawa, M Deshimaru, T Chijiwa, K Nakashima, Y Chuman, Y Shimohigashi, Y Fukumaki, S Hattori, M Ohno

    TOXICON   36 ( 6 )   915 - 920   1998年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    A part of the 3'-flanking region of BP-II gene, which is one of Trimeresurus flavoviridis venom gland phospholopase A(2) (PLA(2)) isozyme genes, has a region homologous to avian chicken repeat 1 (CR1)-element. In the present study, ten CR1-like elements were further identified in T. gramineus venom gland PLA(2) isozyme genes, T. flavoviridis PLA(2) inhibitor (PLI) genes, and T. flavoviridis and T. gramineus TATA-box binding protein (TBP) genes. Southern blot analysis using a probe for CR1 showed that Crotalinae snake genomes contain a number of CR1-like elements. (C) 1998 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0041-0101(97)00104-9

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  • Discrimination of a novel type of rat brain ? opioid receptors by enkephalin analog containing structurally constrained cyclopropylphenylalanine (▽Phe). 査読

    Chuman, Y, Yasunaga, T, Costa, T, Shimohigashi, Y

    Biochem. Mol. Biol. Int.   42 ( 6 )   1227 - 1233   1997年9月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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書籍等出版物

  • アプタマー創薬の現状と細胞膜 自動透過性DNAアプタマーの開発

    水沼 正昂, 坂野 彰則, 金子 敦巳, 亘 美佑, 中馬 吉郎( 担当: 共著)

    月刊「細胞」  2020年5月 

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  • 発がん関連酵素に対するDNAアプタマーを用いた新規阻害剤開発と応用

    月刊「細胞」  2019年2月 

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  • 核酸アプタマーを用いた発がん関連酵素に対する新規阻害剤開発と応用

    アグリバイオ  2018年12月 

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  • 発がん関連Ser/Thrホスファターゼに対する新規阻害剤と基質同定法の開発

    ( 担当: 共著)

    Bio Clinica  2018年5月 

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  • 発がん関連Ser/Thrホスファターゼに対する新規阻害剤の開発

    ( 担当: 共著)

    Bio Clinica  2017年12月 

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  • がん原遺伝子産物PPM1Dの細胞がん化機構および創薬を指向した阻害剤

    生化学/日本生化学会  2015年 

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  • アミノ酸リシンに新たな翻訳後修飾

    化学/化学同人  2011年 

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  • 鎮痛および疼痛にかかわる神経ペプチド

    医学のあゆみ/医歯薬出版株式会社  2000年 

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MISC

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講演・口頭発表等

  • Identification of the Binding Molecules for Disease-related Proteins using Adn-based Phage Display Libraries

    Yoshiro CHUMAN

    The 18th AKABORI Conference 2020  2021年3月 

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    記述言語:英語  

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  • Specific Inhibitors for Oncogenic Protein Phosphatase PPM1D Using G-quadruplex-based DNA aptamer library 招待

    Yoshiro CHUMAN

    14th International Conference on Protein Phosphatases  2020年12月 

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  • Development of Cell Penetrating DNA aptamers for Oncogenic Protein Phosphatase PPM1D 招待

    Yoshiro CHUMAN

    The 43th Annual Meeting of the Molecular Biology Society of Japan  2020年12月 

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  • 刺激応答性DNAアプタマー(IRDAptamer)を用いた疾患関連ホスファターゼ阻害剤の開発 招待

    中馬 吉郎

    第93回日本生化学会大会  2020年9月 

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    記述言語:日本語  

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  • Identification of Specific Inhibitors for Oncogenic Protein Phosphatase PPM1D Using Ion-responsive DNA Aptamer (IRDAptamer) Library 招待

    Yoshiro CHUMAN

    The 42th Annual Meeting of the Molecular Biology Society of Japan  2019年12月 

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    記述言語:英語  

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  • Construction of Structurally-Controlled Platform for Identification of Specific Inhibitors against Oncogenic Ser/Thr Protein Phosphatases 招待

    Yoshiro CHUMAN

    2019 Taiwan-Japan Bilateral Conference on Phosphatase (4th)  2019年11月 

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    記述言語:英語  

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  • 細胞内疾患タンパク質を標的可能な刺激応答性DNAアプタマー創薬の開発と応用

    中馬 吉郎

    BioJapan2019  2019年10月 

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  • リン酸化ミミック分子を用いたSer/Thrホスファターゼ活性中心結合分子の開発

    中馬 吉郎

    第9回日本プロテインホスファターゼ研究会  2019年7月 

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  • 抗体模倣分子を用いた機能性分子の開発とポスト抗体薬への展開

    中馬 吉郎

    第6回U-goサロン  2019年6月 

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  • 『化学』の視点から生命現象を理解する:総合大学の利点を生かした分野横断型融合研究の展開 招待

    中馬 吉郎

    自然系研究最前線セミナー  2019年3月 

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    記述言語:日本語  

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  • イオン応答性DNAアプタマー(IRDAptamer)を用いたPPM1D阻害剤の開発 招待

    中馬 吉郎

    生物化学研究会2018  2019年3月 

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    記述言語:日本語  

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  • Specific Inhibitors for Oncogenic PPM1D Phosphatase Using ion-responsive DNA aptamer (IRDAptamer) 招待 国際会議

    CHUMAN Yoshiro

    The 13th International Conference on Protein Phosphatase  2018年10月 

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

    開催地:Tokyo  

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  • Substrate identification method for protein phosphatases using phosphorylation mimic phage display 招待 国際会議

    CHUMAN Yoshiro

    AKABORI Conference 2018  2018年9月 

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

    開催地:Lindau (Germany)  

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  • 発がん関連脱リン酸化酵素を標的とした阻害剤と新規基質同定法の開発 招待

    中馬 吉郎

    N-Hybrid conference 2018  2018年1月 

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    開催地:新潟市  

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  • Development of Specific Inhibitors for Oncogenic PPM1D Phosphatase Using Rigid-scaffold Structural Libraries

    CHUMAN Yoshiro

    The 3rd Japan-Taiwan Bilateral Conference on Protein Phosphatase  2017年11月 

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    開催地:仙台市  

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  • 発がんタンパク質PPM1Dを標的とした刺激応答性アプタマー阻害剤の開発 招待

    中馬 吉郎

    第3回アプタマー研究会  2017年3月 

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    開催地:久留米市  

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  • Screening of binding molecules for Ser/Thr phosphatases from rigid structural libraries 国際会議

    CHUMAN Yoshiro

    The 12th International Conference on Protein Phosphatase  2016年10月 

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

    開催地:Osaka  

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  • 酵素-基質複合体誘導によるSer/Thrホスファターゼ基質同定法の開発と応用 招待

    中馬 吉郎

    第89回日本生化学会  2016年9月 

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    開催地:仙台市  

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  • 立体制約型libraryを用いた疾患関連タンパク質結合分子の同定 招待

    中馬 吉郎

    フォーラム「生命科学談話シリーズ」  2016年4月 

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    開催地:福岡市  

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  • 発癌関連ホスファターゼに対する新規基質同定法と阻害剤の開発 招待

    中馬 吉郎

    第22回ペプチドフォーラム  2016年3月 

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    開催地:金沢市  

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  • PPM1Dホスファターゼ過剰発現による新規発癌機構 招待

    中馬 吉郎

    第46 回 若手ペプチド夏の勉強会  2014年8月 

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    開催地:京都  

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  • ヒトPPM1Dホスファターゼによる染色体不安定化と新規発がん機構 招待

    中馬 吉郎

    第55回新潟生化学懇話会  2014年6月 

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    開催地:長岡市  

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  • 翻訳後修飾酵素の制御異常による発がん機構と抗がん剤の開発 招待

    中馬 吉郎

    グリーンケミストリー第4回研究シンポジウム  2014年3月 

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    開催地:新潟市  

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  • Genome Instability in the Cells Overexpressing p53-inducible Protein Phosphatase PPM1D 招待 国際会議

    CHUMAN Yoshiro

    2nd Taiwan-Japan Bilateral Conference on Protein Phosphatases  2013年12月 

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

    開催地:Taiwan  

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  • p53誘導性ホスファターゼPPM1D研究の新展開

    中馬 吉郎

    生物化学研究会2013  2013年9月 

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    開催地:札幌市  

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  • p53誘導性ホスファターゼPPM1D過剰発現による染色体不安定性機構

    中馬 吉郎

    第86回日本生化学会  2013年9月 

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    開催地:横浜市  

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  • 17q23にコードされたPPM1Dホスファターゼ過剰発現による染色体不安定化

    中馬 吉郎

    第50回 日本生化学会北海道支部会  2013年7月 

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    開催地:札幌市  

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  • Suppression of Breast Cancer Cells Proliferation by a small molecule inhibitor of p53-inducible protein phosphatase PPM1D

    CHUMAN Yoshiro

    5th GCOE international symposium  2012年2月 

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    記述言語:英語  

    開催地:Sapporo  

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  • ヒトPPM1ホスファターゼファミリーにおけるリン酸化アミノ酸および金属イオン指向性

    中馬 吉郎

    第5回 日本プロテインホスファターゼ研究会学術集会  2012年1月 

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    開催地:大阪市  

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産業財産権

  • 細胞内分子を標的とした細胞膜透過型核酸アプタマー

    中馬 吉郎, 金子 敦巳, 亘 美佑

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    出願番号:特願2019-096035  出願日:2019年5月

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  • 発がん原因酵素を標的としたイオン応答性DNAアプタマー

    中馬 吉郎, 金子 敦巳, 亘 美佑

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    出願番号:特願2019-045938  出願日:2019年3月

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  • Monoclonal antibody specifically recognizing modification site after translation of p53 and kit for assaying modification site containing the same

    Kazuyasu Sakaguchi, Yoshiro Chuman, Yasuo Akebiyama, Miho Matsukizono, Maki Watanabe, Junichi Tsutumi

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    出願番号:特願11/910,313  出願日:2006年3月

    発行日:2011年11月

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  • p53翻訳後修飾部位を特異的に認識するモノクローナル抗体、及びその抗体を含む修飾部位測定キット

    坂口 和靖, 中馬 吉郎, 明日山 康生, 松木園 美穂

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    出願番号:特願2007-511193, PCT/JP2006/306921 

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  • プロテインホスファターゼ阻害剤

    坂口 和靖, 谷野 圭持, 中馬 吉郎, 吉村 文彦, 八木 寛陽

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    出願番号:特願2008-262646, PCT出願PCT/JP2009/005128 

    公表番号:WO2010041401 A1 

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受賞

  • 2010年度(第18回) JB論文賞

    2010年  

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    受賞国:日本国

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  • Fellows Award for Research Excellence (FARE) 2003(National Institutes of Health)

    2002年  

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共同研究・競争的資金等の研究

  • 光刺激によりOn/Off制御可能な次世代創薬プラットホームの開発

    研究課題/領域番号:20K21541  2020年7月 - 2023年3月

    日本学術振興会  科学研究費助成事業 挑戦的研究(萌芽)  挑戦的研究(萌芽)

    代表, 中馬 吉郎

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    配分額:6370000円 ( 直接経費:4900000円 、 間接経費:1470000円 )

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  • 薬剤耐性肺炎球菌のin vivo MS解析とキューブ型DNA抗菌薬の開発研究

    研究課題/領域番号:20H03858  2020年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    新潟大学, 医歯学系, 寺尾 豊

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    配分額:17940000円 ( 直接経費:13800000円 、 間接経費:4140000円 )

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  • 細胞膜自動透過性DNAアプタマーの分子基盤解明とポスト抗体医薬への展開

    2019年 - 2021年

    日本学術振興会  基盤研究(B) 

    代表,中馬 吉郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • 外部刺激応答性DNAアプタマーの抗がん剤展開と発がんタンパク質結晶化への応用

    2018年 - 2020年

    日本学術振興会  特別研究員奨励費(DC1) 

    新潟大学,自然科学系,金子 敦巳

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    資金種別:競争的資金

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  • MRSA特異的な3D転換性DNAアプタマー型抗菌薬の構築と開発技術の確立研究

    2018年 - 2019年

    日本学術振興会  挑戦的研究(萌芽) 

    新潟大学, 医歯学系, 寺尾 豊

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    資金種別:競争的資金

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  • 細胞内疾患原因タンパク質を標的とした自動ホーミング分子の開発

    2018年 - 2019年

    新潟大学  U-go グラント 

    代表,中馬 吉郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • 刺激応答性機能分子IRDAptamerを用いた細胞内制御可能な抗がん剤開発

    2017年 - 2018年

    新潟大学  U-go グラント 

    代表,中馬 吉郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • 酵素-基質複合体誘導によるSer/Thrホスファターゼ基質同定法の開発

    2015年 - 2017年

    日本学術振興会  基盤研究(C) 

    代表,中馬 吉郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • 癌抑制タンパク質p53の多量体化と配向化を基盤とした生物イベント制御と機能解明

    2012年 - 2015年

    日本学術振興会  基盤研究(B) 

    北海道大学,理学(系, 研究科, 究院),坂口 和靖

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    資金種別:競争的資金

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  • PPM1Dホスファターゼ過剰発現細胞における染色体分配制御の破綻と分子基盤解明

    2012年 - 2014年

    日本学術振興会  基盤研究(C) 

    代表,中馬 吉郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • p53四量体ドメインおよびエラスチンペプチドを用いた温度可変型機能性タンパク質の創出

    2011年 - 2012年

    日本学術振興会  GCOEプログラム若手研究者研究活動経費 

    代表,中馬 吉郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • 温度制御分子デバイスを用いた発がんタンパク質PPM1D阻害剤のスクリーニング

    2010年 - 2011年

    日本学術振興会  GCOEプログラム若手研究者研究活動経費 

    代表,中馬 吉郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • 腫瘍由来変異と進化に基づく癌抑制タンパク質p53四量体安定性と機能不全閾値の解明

    2009年 - 2012年

    日本学術振興会  基盤研究(B) 

    北海道大学,理学(系, 研究科, 究院),坂口 和靖

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    資金種別:競争的資金

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  • p53誘導性ホスファターゼPPM1Dの細胞周期における新規制御機構の解明

    2009年 - 2010年

    日本学術振興会  GCOEプログラム若手研究者研究活動経費 

    代表,中馬 吉郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • p53誘導性ホスファターゼPPM1Dスプライシング多型による発がん機構の解明

    2008年 - 2010年

    日本学術振興会  若手研究(B) 

    代表,中馬 吉郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • PPM1D特異的阻害剤による乳がん細胞増殖抑制と制御機構の解明

    2008年 - 2009年

    日本学術振興会  GCOEプログラム若手研究者研究活動経費 

    代表,中馬 吉郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • 新規PPM1D阻害剤を用いた抗癌剤併用療法への展開と薬剤作用機構の解明

    2007年 - 2008年

    日本学術振興会  GCOEプログラム若手研究者研究活動経費 

    代表,中馬 吉郎

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

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  • がん抑制タンパク質p53四量体形成変異による不活性化機構の解明と機能修復剤の開発

    2006年 - 2008年

    日本学術振興会  基盤研究(B) 

    北海道大学,理学(系, 研究科, 究院),坂口 和靖

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    資金種別:競争的資金

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  • p53誘導性ホスファターゼPPM1Dの機能解析用分子ツールとしての阻害剤開発

    2005年 - 2007年

    日本学術振興会  若手研究(B) 

    代表,中馬 吉郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • がん抑制タンパク質p53の四量体形成ドメインのフォールディング

    2004年 - 2005年

    日本学術振興会  特定領域研究 

    北海道大学,理学(系, 研究科, 究院),坂口 和靖

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    資金種別:競争的資金

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  • エンケファリン内蔵の変異オピオイド受容体による受容体分子機構の解明

    1998年 - 2000年

    日本学術振興会  特別研究員奨励費 

    代表,中馬 吉郎

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

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担当経験のある授業科目

  • 化学特論III

    2021年
    -
    現在
    機関名:新潟大学

  • 課題研究 a

    2020年
    -
    現在
    機関名:新潟大学

  • 課題研究 b

    2020年
    -
    現在
    機関名:新潟大学

  • 理学スタディ・スキルズ

    2019年
    機関名:新潟大学

  • 科学技術英語

    2018年
    機関名:新潟大学

  • コミュニケーション演習

    2018年
    機関名:新潟大学

  • 自然科学基礎実験

    2017年
    -
    現在
    機関名:新潟大学

  • 課題研究

    2017年
    -
    現在
    機関名:新潟大学

  • 化学基礎実習a

    2017年
    -
    現在
    機関名:新潟大学

  • 化学基礎実習b

    2017年
    -
    現在
    機関名:新潟大学

  • 生体分子化学Ⅱ

    2017年
    -
    現在
    機関名:新潟大学

  • Advances in Physics and Chemistry

    2017年
    機関名:新潟大学

  • 化学コロキウム

    2017年
    機関名:新潟大学

  • 数理物質科学演習Ⅰ(化学)

    2015年
    機関名:新潟大学

  • 数理物質科学特定研究Ⅰ(化学)

    2015年
    機関名:新潟大学

  • 安全教育

    2015年
    機関名:新潟大学

  • 分子生理化学

    2014年
    -
    現在
    機関名:新潟大学

  • 生化学演習

    2014年
    -
    現在
    機関名:新潟大学

  • 生化学実験

    2014年
    -
    現在
    機関名:新潟大学

  • グリーンケミストリー入門

    2014年
    -
    現在
    機関名:新潟大学

  • 生理機能化学

    2014年
    -
    現在
    機関名:新潟大学

  • 化学実験

    2014年
    -
    2016年
    機関名:新潟大学

  • 生体分子化学II

    2014年
    -
    2016年
    機関名:新潟大学

  • 課題研究(化学科)

    2014年
    -
    2016年
    機関名:新潟大学

▶ 全件表示

 

社会貢献活動

  • 高大連携 出前講義(科研費アウトリーチ等)

    役割:講師

    新潟県立 長岡高等学校 出前講義(オンライン)  2021年7月

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  • 高大連携 出前講義(科研費アウトリーチ等)

    役割:講師

    学校法人静岡理工科大学 星陵高等学校 出前講義 (オンライン)  2021年6月

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  • 高大連携 出前講義(科研費アウトリーチ等)

    役割:講師

    新潟県立高田高等学校  2018年9月

     詳細を見る

  • 高校生のためのシンポジウム

    役割:講師

    新潟大学  新潟大学教育研究特別シンポジウム  2018年7月

     詳細を見る

  • 高大連携 出前講義(科研費アウトリーチ等)

    役割:講師

    山形県立山形西高等学校  2017年7月

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  • 高大連携 出前講義(科研費アウトリーチ等)

    役割:講師

    長野県諏訪双葉高校  2016年10月

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  • 高大連携 出前講義(科研費アウトリーチ等)

    役割:講師

    新潟県立柏崎翔陽中等教育学校  2016年7月

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  • 高大連携 出前講義(科研費アウトリーチ等)

    役割:講師

    栃木県立栃木高等学校  2016年7月

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▶ 全件表示