Updated on 2026/03/05

写真a

 
SAKAMOTO Satoshi
 
Organization
School of Life Science and Technology Assistant Professor
Title
Assistant Professor
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Degree

  • 博士（理学） ( 東北大学 )

Research Areas

  • Life Science / Bioorganic chemistry

Education

  • Tohoku University   Graduate School of Science   Department of Chemistry

    1998.4 - 2003.3

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  • Tohoku University   Faculty of Science   Department of Chemistry

    1994.4 - 1998.3

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Papers

  • Application of Magnetic Nanoparticle in Cancer Surgery—Sentinel Node Mapping and Magnetically Promoted Rapid Immunofluorescence Staining—

    Mihara Kisyo, Onishi Tatsuya, Matsuda Sachiko, Sakamoto Satoshi, Handa Hiroshi, Kuwahata Akihiro, Sekino Masaki, Kusakabe Moriaki, Kitagawa Yuko

    IEEJ Transactions on Fundamentals and Materials   142 ( 6 )   236 - 242   2022.6

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    Language：Japanese   Publisher：The Institute of Electrical Engineers of Japan  

    Recently, there has been remarkable progress in the field of magnetic nanoparticles, with them now being applied in cancer surgery. During tumor surgery, lymph node dissection is required along with tumor resection. However, in cases such as breast cancer, lymph node dissection can be omitted if no metastasis is found in the sentinel lymph node (SLN; the first draining lymph node from a primary tumor), thereby reducing postoperative sequelae. The presence or absence of SN metastasis alters the surgical procedure; therefore, intraoperative SLN mapping and rapid pathological SLN diagnosis are required. The standard procedure of SLN mapping is a combination of radioisotope and dye methods, but radioisotope methods have problems associated with regulation and safety. To overcome these problems, a SLN mapping method using magnetic nanoparticles has been developed. This technique has already been clinically applied to breast cancer. In this article, a laparoscopic magnetic probe was developed to expand the SLN theory to visceral organs such as the stomach and gallbladder. A preclinical study of SLN mapping was feasible in laparoscopic minimally invasive surgery. Although resected sentinel lymph nodes can be rapidly diagnosed intraoperatively, the diagnostic accuracy of hematoxylin and eosin staining is limited. Conversely, immunohistochemistry, which gives additional information to pathologists by staining particular proteins, has not yet been used for rapid diagnostics because of the time required for staining. A new rapid immunostaining method is magnetically-promoted rapid immunofluorescence staining using functionalized fluorescent ferrite beads. The antigen-antibody reaction is accelerated by magnetic force, and antigen-antibody complexes can be directly observed with a fluorescence microscope. We have succeeded in diagnosing frozen sections within 15 min from fixation to staining. To realize minimally invasive surgery, a detailed understanding of tumor development is essential, and nanotechnology is being applied in this field to address this issue. In this paper, we introduce a SLN biopsy and rapid immunostaining method based on magnetic nanoparticle technology to further this field.

    DOI： 10.1541/ieejfms.142.236

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  • Application of Magnetic Nanoparticles for Rapid Detection and In Situ Diagnosis in Clinical Oncology Reviewed

    Tatsuya Onishi, Kisyo Mihara, Sachiko Matsuda, Satoshi Sakamoto, Akihiro Kuwahata, Masaki Sekino, Moriaki Kusakabe, Hiroshi Handa, Yuko Kitagawa

    Cancers   14 ( 2 )   364 - 364   2022.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.3390/cancers14020364

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  • Application of Magnetic Nanoparticles for Rapid Detection and In Situ Diagnosis in Clinical Oncology. International journal

    Tatsuya Onishi, Kisyo Mihara, Sachiko Matsuda, Satoshi Sakamoto, Akihiro Kuwahata, Masaki Sekino, Moriaki Kusakabe, Hiroshi Handa, Yuko Kitagawa

    Cancers   14 ( 2 )   2022.1

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    Screening, monitoring, and diagnosis are critical in oncology treatment. However, there are limitations with the current clinical methods, notably the time, cost, and special facilities required for radioisotope-based methods. An alternative approach, which uses magnetic beads, offers faster analyses with safer materials over a wide range of oncological applications. Magnetic beads have been used to detect extracellular vesicles (EVs) in the serum of pancreatic cancer patients with statistically different EV levels in preoperative, postoperative, and negative control samples. By incorporating fluorescence, magnetic beads have been used to quantitatively measure prostate-specific antigen (PSA), a prostate cancer biomarker, which is sensitive enough even at levels found in healthy patients. Immunostaining has also been incorporated with magnetic beads and compared with conventional immunohistochemical methods to detect lesions; the results suggest that immunostained magnetic beads could be used for pathological diagnosis during surgery. Furthermore, magnetic nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs), can detect sentinel lymph nodes in breast cancer in a clinical setting, as well as those in gallbladder cancer in animal models, in a surgery-applicable timeframe. Ultimately, recent research into the applications of magnetic beads in oncology suggests that the screening, monitoring, and diagnosis of cancers could be improved and made more accessible through the adoption of this technology.

    DOI： 10.3390/cancers14020364

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  • UGGT1 retains proinsulin in the endoplasmic reticulum in an arginine dependent manner. International journal

    Jaeyong Cho, Masaki Hiramoto, Yuka Masaike, Satoshi Sakamoto, Yoichi Imai, Yumi Imai, Hiroshi Handa, Takeshi Imai

    Biochemical and biophysical research communications   527 ( 3 )   668 - 675   2020.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    We sought to clarify a pathway by which L- and dD-arginine simulate insulin secretion in mice and cell lines and obtained the following novel two findings. (1) Using affinity magnetic nanobeads technology, we identified that proinsulin is retained in the endoplasmic reticulum (ER) through UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) when arginine availability is limited. (2) L- and d-arginine release proinsulin from UGGT1 through competition with proinsulin and promote exit of proinsulin from the ER to Golgi apparatus. The ability of arginine to release proinsulin from UGGT1 closely correlates with arginine-induced insulin secretion in several models of β cells indicating that UGGT1-proinsulin interaction regulates arginine-induced insulin secretion.

    DOI： 10.1016/j.bbrc.2020.04.158

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  • Genome-wide screening reveals a role for subcellular localization of CRBN in the anti-myeloma activity of pomalidomide. Reviewed International journal

    Shumpei Tateno, Midori Iida, Satoshi Fujii, Tetsufumi Suwa, Miki Katayama, Haruka Tokuyama, Junichi Yamamoto, Takumi Ito, Satoshi Sakamoto, Hiroshi Handa, Yuki Yamaguchi

    Scientific reports   10 ( 1 )   4012 - 4012   2020.3

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    Pomalidomide, a derivative of thalidomide, is an effective treatment for multiple myeloma. The drug exerts its effects through CRBN, a component of the E3 ubiquitin ligase complex CRL4CRBN. To search for novel factors involved in the anti-cancer activity of pomalidomide, we performed a genome-wide shRNA library screen and identified 445 genes as those affecting pomalidomide sensitivity. Genes encoding components of the ubiquitin-proteasome pathway, such as subunits of the CRL4CRBN complex, the COP9 signalosome, and the 26S proteasome, were among the pomalidomide-affecting genes. Karyopherin beta 1 (KPNB1) was identified as a novel pomalidomide-affecting gene. KPNB1 was required for the nuclear import of CRBN and for the CRBN-directed, pomalidomide-dependent degradation of a clinically relevant substrate, the transcription factor Aiolos. By contrast, the cytoplasmic translation factor GSPT1 was degraded following treatment with the thalidomide derivative CC-885 only when CRBN was present in the cytoplasm, indicating that subcellular distribution of CRBN is critical for the efficacy of thalidomide-based medications.

    DOI： 10.1038/s41598-020-61027-w

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  • Development of an optimized dome-shaped magnet for rapid magnetic immunostaining

    Masaki Sekino, Akihiro Kuwahata, Shunsuke Fujita, Sachiko Matsuda, Miki Kaneko, Shinichi Chikaki, Satoshi Sakamoto, Itsuro Saito, Hiroshi Handa, Moriaki Kusakabe

    AIP ADVANCES   10 ( 2 )   2020.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1063/1.5130516

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  • Development of an automatic magnetic immunostaining system for rapid intraoperative diagnosis of cancer metastasis

    Masaki Sekino, Akihiro Kuwahata, Akinobu Yoshibe, Kiyotaka Imai, Miki Kaneko, Shinichi Chikaki, Itsuro Saito, Akinori Tsuruma, Satoshi Sakamoto, Hiroshi Handa, Sachiko Matsuda, Moriaki Kusakabe

    AIP ADVANCES   10 ( 1 )   2020.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1063/1.5130478

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  • Magnetically Promoted Rapid Immunofluorescence Staining for Frozen Tissue Sections. International journal

    Tatsuya Onishi, Sachiko Matsuda, Yuki Nakamura, Junko Kuramoto, Akinori Tsuruma, Satoshi Sakamoto, Shunichi Suzuki, Daiichiro Fuchimoto, Akira Onishi, Shinichi Chikaki, Miki Kaneko, Akihiro Kuwahata, Masaki Sekino, Hiroshi Yasuno, Naohiro Hanyu, Tomoko Kurita, Hiroyuki Takei, Takashi Sakatani, Kanae Taruno, Seigo Nakamura, Tetsu Hayashida, Hiromitsu Jinno, Moriaki Kusakabe, Hiroshi Handa, Kaori Kameyama, Yuko Kitagawa

    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society   67 ( 8 )   575 - 587   2019.8

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    Current immunohistochemistry methods for diagnosing abnormal cells, such as cancer cells, require multiple steps and can be relatively slow compared with intraoperative frozen hematoxylin and eosin staining, and are therefore rarely used for intraoperative examination. Thus, there is a need for novel rapid detection methods. We previously demonstrated that functionalized fluorescent ferrite beads (FF beads) magnetically promoted rapid immunoreactions. The aim of this study was to improve the magnetically promoted rapid immunoreaction method using antibody-coated FF beads and a magnet subjected to a magnetic field. Using frozen sections of xenograft samples of A431 human epidermoid cancer cells that express high levels of epidermal growth factor receptor (EGFR) and anti-EGFR antibody-coated FF beads, we reduced the magnetically promoted immunohistochemistry procedure to a 1-min reaction and 1-min wash. We also determined the optimum magnetic force for the antibody reaction (from 7.79 × 10-15 N to 3.35 × 10-15 N) and washing (4.78 × 10-16 N), which are important steps in this technique. Furthermore, we stained paraffin-embedded tissue arrays and frozen sections of metastatic breast cancer lymph nodes with anti-pan-cytokeratin antibody-coated FF beads to validate the utility of this system in clinical specimens. Under optimal conditions, this ultra-rapid immunostaining method may provide an ancillary method for pathological diagnosis during surgery. (J Histochem Cytochem 58:XXX-XXX, 2010).

    DOI： 10.1369/0022155419841023

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  • Cereblon Control of Zebrafish Brain Size by Regulation of Neural Stem Cell Proliferation. Reviewed International journal

    Hideki Ando, Tomomi Sato, Takumi Ito, Junichi Yamamoto, Satoshi Sakamoto, Nobuhiro Nitta, Tomoko Asatsuma-Okumura, Nobuyuki Shimizu, Ryota Mizushima, Ichio Aoki, Takeshi Imai, Yuki Yamaguchi, Arnold J Berk, Hiroshi Handa

    iScience   15   95 - 108   2019.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    Thalidomide is a teratogen that causes multiple malformations in the developing baby through its interaction with cereblon (CRBN), a substrate receptor subunit of the CRL4 E3 ubiquitin ligase complex. CRBN was originally reported as a gene associated with autosomal recessive non-syndromic mild mental retardation. However, the function of CRBN during brain development remains largely unknown. Here we demonstrate that CRBN promotes brain development by facilitating the proliferation of neural stem cells (NSCs). Knockdown of CRBN in zebrafish embryos impaired brain development and led to small brains, as did treatment with thalidomide. By contrast, overexpression of CRBN resulted in enlarged brains, leading to the expansion of NSC regions and increased cell proliferation in the early brain field and an expanded expression of brain region-specific genes and neural and glial marker genes. These results demonstrate that CRBN functions in the determination of brain size by regulating the proliferation of NSCs during development.

    DOI： 10.1016/j.isci.2019.04.007

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  • Application of high-performance magnetic nanobeads to biological sensing devices. Reviewed International journal

    Kabe Y, Sakamoto S, Hatakeyama M, Yamaguchi Y, Suematsu M, Itonaga M, Handa H

    Analytical and bioanalytical chemistry   411 ( 9 )   1825 - 1837   2019.1

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    Nanomaterials have extensive applications in the life sciences and in clinical diagnosis. We have developed magnetic nanoparticles with high dispersibility and extremely low nonspecific binding to biomolecules and have demonstrated their application in chemical biology (e.g., for the screening of drug receptor proteins). Recently, the excellent properties of nanobeads have made possible the development of novel rapid immunoassay systems and high-precision technologies for exosome detection. For immunoassays, we developed a technology to encapsulate a fluorescent substance in magnetic nanobeads. The fluorescent nanobeads allow the rapid detection of a specific antigen in solution or in tissue specimens. Exosomes, which are released into the blood, are expected to become markers for several diseases, including cancer, but techniques for measuring the absolute quantity of exosomes in biological fluids are lacking. By integrating magnetic nanobead technology with an optical disc system, we developed a novel method for precisely quantifying exosomes in human serum with high sensitivity and high linearity without requiring enrichment procedures. This review focuses on the properties of our magnetic nanobeads, the development of novel biosensors using these nanobeads, and their broad practical applications. Graphical abstract ᅟ.

    DOI： 10.1007/s00216-018-1548-y

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  • Structural basis of thalidomide enantiomer binding to cereblon Reviewed

    Tomoyuki Mori, Takumi Ito, Shujie Liu, Hideki Ando, Satoshi Sakamoto, Yuki Yamaguchi, Etsuko Tokunaga, Norio Shibata, Hiroshi Handa, Toshio Hakoshima

    Scientific Reports   8 ( 1 )   1294   2018.12

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    DOI： 10.1038/s41598-018-19202-7

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  • Development of a Highly Sensitive Device for Counting the Number of Disease-Specific Exosomes in Human Sera. Reviewed

    Kabe Y, Suematsu M, Sakamoto S, Hirai M, Koike I, Hishiki T, Matsuda A, Hasegawa Y, Tsujita K, Ono M, Minegishi N, Hozawa A, Murakami Y, Kubo M, Itonaga M, Handa H

    Clinical chemistry   64 ( 10 )   1463 - 1473   2018.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1373/clinchem.2018.291963

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  • Development of magnet configurations for magnetic immunostaining Reviewed

    Miki Kaneko, Shinichi Chikaki, Sachiko Matsuda, Akihiro Kuwahata, Masayuki Namita, Itsuro Saito, Satoshi Sakamoto, Moriaki Kusakabe, Masaki Sekino

    AIP Advances   8 ( 5 )   2018.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1063/1.5007918

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  • Development of a Rapid Magnetic Immunostaining System Using Antibody-Labelled Fluorescent Magnetic Beads

    坂本 聡, 半田 宏

    まぐね = Magnetics Japan   13 ( 4 )   167 - 173   2018

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    Language：Japanese   Publisher：日本応用磁気学会  

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  • The Neuroprotective Marine Compound Psammaplysene A Binds the RNA-Binding Protein HNRNPK Reviewed

    Boccitto M, Lee N, Sakamoto S, Spruce LA, Handa H, Clardy J, Seeholzer SH, Kalb RG

    Marine Drugs   15 ( 8 )   2017.8

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    DOI： 10.3390/md15080246

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  • Application of affinity purification of drug target proteins with practical magnetic nanoparticles to drug development

    Takumi Ito, Satoshi Sakamoto, Hiroshi Handa

    Nanoscale Fabrication, Optimization, Scale-up and Biological Aspects of Pharmaceutical Nanotechnology   479 - 510   2017.1

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    Language：English   Publishing type：Part of collection (book)   Publisher：Elsevier  

    DOI： 10.1016/B978-0-12-813629-4.00012-7

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  • Macrolides sensitize EGFR-TKI-induced non-apoptotic cell death via blocking autophagy flux in pancreatic cancer cell lines Reviewed

    Shuntaro Mukai, Shota Moriya, Masaki Hiramoto, Hiromi Kazama, Hiroko Kokuba, Xiao-Fang Che, Tomohisa Yokoyama, Satoshi Sakamoto, Akihiro Sugawara, Toshiaki Sunazuka, Satoshi Omura, Hiroshi Handa, Takao Itoi, Keisuke Miyazawa

    INTERNATIONAL JOURNAL OF ONCOLOGY   48 ( 1 )   45 - 54   2016.1

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    DOI： 10.3892/ijo.2015.3237

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  • A Trifluorinated Thiazoline Scaffold Leading to Pro-apoptotic Agents Targeting Prohibitins Reviewed

    Alba Perez-Perarnau, Sara Preciado, Claudia Mariela Palmeri, Cristina Moncunill-Massaguer, Daniel Iglesias-Serret, Diana M. Gonzalez-Girones, Miriam Miguel, Satoki Karasawa, Satoshi Sakamoto, Ana M. Cosialls, Camila Rubio-Patino, Jose Saura-Esteller, Rosario Ramon, Laia Caja, Isabel Fabregat, Gabriel Pons, Hiroshi Handa, Fernando Albericio, Joan Gil, Rodolfo Lavilla

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   53 ( 38 )   10150 - 10154   2014.9

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    DOI： 10.1002/anie.201405758

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  • Magnetically Promoted Rapid Immunoreactions Using Functionalized Fluorescent Magnetic Beads: A Proof of Principle Reviewed

    Satoshi Sakamoto, Kenshi Omagari, Yoshinori Kita, Yusuke Mochizuki, Yasuyuki Naito, Shintaro Kawata, Sachiko Matsuda, Osamu Itano, Hiromitsu Jinno, Hiroya Takeuchi, Yuki Yamaguchi, Yuko Kitagawa, Hiroshi Handa

    CLINICAL CHEMISTRY   60 ( 4 )   610 - 620   2014.4

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    DOI： 10.1373/clinchem.2013.211433

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  • A Novel Aromatic Carboxylic Acid Inhibits Luciferase Enzymatic Activity in Mammalian Cells by Acylation of an Active Regulatory Lysine Residue Reviewed

    Madoka Nakagomi, Koichi Shudo, Satoshi Sakamoto, Hiroshi Handa, Takeo Iwamoto, Tomokazu Matsuura

    BIOPHYSICAL JOURNAL   106 ( 2 )   263A - 263A   2014.1

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  • Single nanobeads detection by scaninng laser spot for immunosensing. Reviewed

    Tsujita K, Hasegawa Y, Ono M, Itonaga M, Kabe Y, Sakamoto S, Handa H

    MicroTAS   3   2297 - 2299   2014

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  • In Vivo Identification of Sentinel Lymph Nodes Using MRI and Size-Controlled and Monodispersed Magnetite Nanoparticles Reviewed

    Shuji Iida, Kensuke Imai, Sachiko Matsuda, Osamu Itano, Mamoru Hatakeyama, Satoshi Sakamoto, Daisuke Kokuryo, Koji Okabayashi, Takashi Endo, Yoshiyuki Ishii, Hirotoshi Hasegawa, Ichio Aoki, Hiroshi Handa, Yuko Kitagawa

    JOURNAL OF MAGNETIC RESONANCE IMAGING   38 ( 6 )   1346 - 1355   2013.12

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    DOI： 10.1002/jmri.24108

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  • Salicylic Acid Induces Mitochondrial Injury by Inhibiting Ferrochelatase Heme Biosynthesis Activity Reviewed

    Vipul Gupta, Shujie Liu, Hideki Ando, Ryohei Ishii, Shumpei Tateno, Yuki Kaneko, Masato Yugami, Satoshi Sakamoto, Yuki Yamaguchi, Osamu Nureki, Hiroshi Handa

    MOLECULAR PHARMACOLOGY   84 ( 6 )   824 - 833   2013.12

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    DOI： 10.1124/mol.113.087940

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  • Ultrahigh-Sensitivity Biomarker Sensing System Based on the Combination of Optical Disc Technologies and Nanobead Technologies Reviewed

    Koji Tsujita, Yuichi Hasegawa, Masayuki Ono, Makoto Itonaga, Satoshi Sakamoto, Mamoru Hatakeyama, Hiroshi Handa

    JAPANESE JOURNAL OF APPLIED PHYSICS   52 ( 9 )   2013.9

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    DOI： 10.7567/JJAP.52.09LB02

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  • Viral protein-coating of magnetic nanoparticles using simian virus 40 VP1 Reviewed

    Teruya Enomoto, Masaaki Kawano, Hajime Fukuda, Wataru Sawada, Takamasa Inoue, Kok Chee Haw, Yoshinori Kita, Satoshi Sakamoto, Yuki Yamaguchi, Takeshi Imai, Mamoru Hatakeyama, Shigeyoshi Saito, Adarsh Sandhu, Masanori Matsui, Ichio Aoki, Hiroshi Handa

    JOURNAL OF BIOTECHNOLOGY   167 ( 1 )   8 - 15   2013.8

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    DOI： 10.1016/j.jbiotec.2013.06.005

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  • Vesnarinone suppresses TNFa mRNA expression by inhibiting valosin-containing protein Reviewed

    Kentaro Hotta, Akihiro Nashimoto, Eiji Yasumura, Masafumi Suzuki, Motoki Azuma, Yosuke Iizumi, Daisuke Shima, Ryusuke Nabeshima, Masaki Hiramoto, Akira Okada, Kumiko Sakata-Sogawa, Makio Tokunaga, Takumi Ito, Hideki Ando, Satoshi Sakamoto, Yasuaki Kabe, Shinichi Aizawa, Takeshi Imai, Yuki Yamaguchi, Hajime Watanabe, Hiroshi Handa

    Molecular Pharmacology   83 ( 5 )   930 - 938   2013.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1124/mol.112.081935

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  • Vitamin K2 Covalently Binds to Bak and Induces Bak-Mediated Apoptosis Reviewed

    Satoki Karasawa, Motoki Azuma, Takeshi Kasama, Satoshi Sakamoto, Yasuaki Kabe, Takeshi Imai, Yuki Yamaguchi, Keisuke Miyazawa, Hiroshi Handa

    MOLECULAR PHARMACOLOGY   83 ( 3 )   613 - 620   2013.3

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    DOI： 10.1124/mol.112.082602

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  • Identification of DNA-Dependent Protein Kinase Catalytic Subunit (DNA-PKcs) as a Novel Target of Bisphenol A Reviewed

    Yuki Ito, Takumi Ito, Satoki Karasawa, Teruya Enomoto, Akihiro Nashimoto, Yasuyoshi Hase, Satoshi Sakamoto, Tsuneyo Mimori, Yoshihisa Matsumoto, Yuki Yamaguchi, Hiroshi Handa

    PLOS ONE   7 ( 12 )   e50481   2012.12

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    DOI： 10.1371/journal.pone.0050481

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  • Tools and methodologies capable of isolating and identifying a target molecule for a bioactive compound Reviewed

    Satoshi Sakamoto, Mamoru Hatakeyama, Takumi Ito, Hiroshi Handa

    BIOORGANIC & MEDICINAL CHEMISTRY   20 ( 6 )   1990 - 2001   2012.3

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    DOI： 10.1016/j.bmc.2011.12.022

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  • High-performance affinity purification for identification of 15-deoxy-Delta(12,14)-PGJ(2) interacting factors using magnetic nanobeads Reviewed

    Naoya Maekawa, Masaki Hiramoto, Satoshi Sakamoto, Motoki Azuma, Takumi Ito, Marie Ikeda, Michitaka Naitou, Hukum P. Acharya, Yuichi Kobayashi, Makoto Suematsu, Hiroshi Handa, Takeshi Imai

    BIOMEDICAL CHROMATOGRAPHY   25 ( 4 )   466 - 471   2011.4

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    DOI： 10.1002/bmc.1469

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  • A two-step ligand exchange reaction generates highly water-dispersed magnetic nanoparticles for biomedical applications Reviewed

    Mamoru Hatakeyama, Hiroshi Kishi, Yoshinori Kita, Kensuke Imai, Kosuke Nishio, Satoki Karasawa, Yuka Masaike, Satoshi Sakamoto, Adarsh Sandhu, Akihiro Tanimoto, Tatsuya Gomi, Eiichi Kohda, Masanori Abe, Hiroshi Handa

    JOURNAL OF MATERIALS CHEMISTRY   21 ( 16 )   5959 - 5966   2011

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    DOI： 10.1039/c0jm04381h

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  • Identification and Formation of Volatile Components Responsible for the Characteristic Aroma of Mat Rush (Igusa) Reviewed

    Kenji Kumazawa, Nao Sakai, Hiroko Amma, Satoshi Sakamoto, Masaki Kodama, Yoshiyuki Wada, Osamu Nishimura

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   74 ( 6 )   1231 - 1236   2010.6

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    DOI： 10.1271/bbb.100053

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  • Identification of Dynamin-2-Mediated Endocytosis as a New Target of Osteoporosis Drugs, Bisphosphonates Reviewed

    Yuka Masaike, Takeshi Takagi, Masataka Hirota, Joe Yamada, Satoru Ishihara, Tetsu M. C. Yung, Takamasa Inoue, Chika Sawa, Hiroshi Sagara, Satoshi Sakamoto, Yasuaki Kabe, Yasuyuki Takahashi, Yuki Yamaguchi, Hiroshi Handa

    MOLECULAR PHARMACOLOGY   77 ( 2 )   262 - 269   2010.2

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    DOI： 10.1124/mol.109.059006

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  • Identification of Dynamin-2-Mediated Endocytosis as a New Target of Osteoporosis Drugs, Bisphosphonates Reviewed

    Yuka Masaike, Takeshi Takagi, Masataka Hirota, Joe Yamada, Satoru Ishihara, Tetsu M. C. Yung, Takamasa Inoue, Chika Sawa, Hiroshi Sagara, Satoshi Sakamoto, Yasuaki Kabe, Yasuyuki Takahashi, Yuki Yamaguchi, Hiroshi Handa

    Molecular Pharmacology   77 ( 2 )   262 - 269   2010.2

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    DOI： 10.1124/mol.109.059006

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  • Study on recycling of waste water from spent water-soluble coolant Reviewed

    Kazuya Takada, Yasuo Kondo, Kenji Yamaguchi, Satoshi Sakamoto

    JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY   24 ( 1 )   267 - 270   2010.1

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    DOI： 10.1007/s12206-009-1160-3

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  • Detection of 8 nm Diameter Superparamagnetic Beads by Magnetically-Induced Manipulation of Micrometer-Sized Magnetic Beads: A Novel Protocol for Magnetically-Labeled Biosensing Reviewed

    Yoshitaka Morimoto, Tsukasa Takamura, Sang Yoon Park, Satoshi Sakamoto, Shintaro Kawata, Hiroshi Handa, Adarsh Sandhu

    JAPANESE JOURNAL OF APPLIED PHYSICS   49 ( 4 )   2010

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    DOI： 10.1143/JJAP.49.04DL07

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  • Inhibitory Effect of N,N-Didesmethylgrossularine-1 on Inflammatory Cytokine Production in Lipopolysaccharide-Stimulated RAW 264.7 Cells Reviewed

    Taiko Oda, Jong-Soo Lee, Yuta Sato, Yasuaki Kabe, Satoshi Sakamoto, Hiroshi Handa, Remy E. P. Mangindaan, Michio Namikoshi

    MARINE DRUGS   7 ( 4 )   589 - 599   2009.12

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    DOI： 10.3390/md7040589

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  • Novel Applications of Affinity Beads Reviewed

    Yasuaki Kabe, Mamoru Hatakeyama, Satoshi Sakamoto, Kosuke Nishio, Hiroshi Handa

    Protein Targeting with Small Molecules: Chemical Biology Techniques and Applications   39 - 56   2009.8

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    DOI： 10.1002/9780470495018.ch3

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  • Spongipyran synthetic studies. Evolution of a scalable total synthesis of (+)-spongistatin 1 Reviewed

    Amos B. Smith, Chris Sfouggatakis, Christina A. Risatti, Jeffrey B. Sperry, Wenyu Zhu, Victoria A. Doughty, Takashi Tomioka, Dimitar B. Gotchev, Clay S. Bennett, Satoshi Sakamoto, Onur Atasoylu, Shohei Shirakami, David Bauer, Makoto Takeuchi, Jyunichi Koyanagi, Yasuharu Sakamoto

    TETRAHEDRON   65 ( 33 )   6489 - 6509   2009.8

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    DOI： 10.1016/j.tet.2009.04.003

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  • Characterization of a magnetic carrier encapsulating europium and ferrite nanoparticles for biomolecular recognition and imaging Reviewed

    Mamoru Hatakeyama, Yusuke Mochizuki, Yoshinori Kita, Hiroshi Kishi, Kosuke Nishio, Satoshi Sakamoto, Masanori Abe, Hiroshi Handa

    JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS   321 ( 10 )   1364 - 1367   2009.5

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    DOI： 10.1016/j.jmmm.2009.02.039

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  • Development and Application of High-Performance Affinity Beads: Toward Chemical Biology and Drug Discovery Reviewed

    Satoshi Sakamoto, Yasuaki Kabe, Mamoru Hatakeyama, Yuki Yamaguchi, Hiroshi Handa

    CHEMICAL RECORD   9 ( 1 )   66 - 85   2009

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    DOI： 10.1002/tcr.20170

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  • Affinity magnetic beads for Chemical Biology and medicine. Reviewed

    Izumi Y, Kabe Y, Hatakeyama M, Sakamoto S, Handa H

    Colloids in Biotechnological Applications   152   197 - 207   2009

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  • Development of novel magnetic nano-carriers for high-performance affinity purification Reviewed

    Kosuke Nishio, Yuka Masaike, Morihito Ikeda, Hiroki Narimatsu, Nobuyuki Gokon, Shingo Tsubouchi, Mamoru Hatakeyama, Satoshi Sakamoto, Naohiro Hanyu, Adarsh Sandhu, Haruma Kawaguchi, Masanori Abe, Hiroshi Handa

    COLLOIDS AND SURFACES B-BIOINTERFACES   64 ( 2 )   162 - 169   2008.7

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    DOI： 10.1016/j.colsurfb.2008.01.013

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  • Sensitivity dependence of Hall biosensor arrays with the position of superparamagnetic beads on their active regions Reviewed

    Yoshimichi Kumagai, Yasuharu Imai, Masanori Abe, Satoshi Sakamoto, Hiroshi Handa, Adarsh Sandhu

    JOURNAL OF APPLIED PHYSICS   103 ( 7 )   2675 - 2677   2008.4

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    DOI： 10.1063/1.2833306

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  • Development of a chemical screening system using aqueorin-fused protein Reviewed

    Masafumi Suzuki, Shoichiro Furukawa, Chikanori Kuramori, Chika Sawa, Yasuaki Kabe, Mitsuhiro Nakamura, Jun-ichi Sawada, Yuki Yamaguchi, Satoshi Sakamoto, Satoshi Inouye, Hiroshi Handa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   368 ( 3 )   600 - 605   2008.4

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    DOI： 10.1016/j.bbrc.2008.01.107

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  • High efficiency Hall effect micro-biosensor platform for detection of magnetically labeled biomolecules Reviewed

    Adarsh Sandhu, Yoshimichi Kumagai, Adam Lapicki, Satoshi Sakamoto, Masanori Abe, Hiroshi Handa

    BIOSENSORS & BIOELECTRONICS   22 ( 9-10 )   2115 - 2120   2007.4

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    DOI： 10.1016/j.bios.2006.09.021

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  • Identification of a chemical substructure that is immobilized to ferrite nanoparticles (FP) Reviewed

    Kosuke Nishio, Nobuyuki Gokon, Makoto Hasegawa, Yuji Ogura, Morihito Ikeda, Hiroki Narimatsu, Masaru Tada, Yuki Yamaguchi, Satoshi Sakamoto, Masanori Abe, Hiroshi Handa

    COLLOIDS AND SURFACES B-BIOINTERFACES   54 ( 2 )   249 - 253   2007.2

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    DOI： 10.1016/j.colsurfb.2006.10.039

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  • Polymer Particles as the Carrier for Affinity Purification

    HATAKEYAMA Mamoru, NISHIO Kosuke, NAKAMURA Mitsuhiro, SAKAMOTO Satoshi, KABE Yasuaki, WADA Tadashi, HANDA Hiroshi

    KOBUNSHI RONBUNSHU   64 ( 1 )   9 - 20   2007

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  • Hall biosensor with integrated current microstrips for control of magnetic beads Reviewed

    Yoshimichi Kumagai, Kiyoshi Togawa, Satoshi Sakamoto, Masanori Abe, Hiroshi Handa, Adarsh Sandhu

    IEEE TRANSACTIONS ON MAGNETICS   42 ( 12 )   3893 - 3895   2006.12

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    DOI： 10.1109/TMAG.2006.879613

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  • Direct detection of redox reactions of sulfur-containing compounds on ferrite nanoparticle (FP) surface Reviewed

    Kosuke Nishio, Nobuyuki Gokon, Shingo Tsubouchi, Morihito Ikeda, Hiroki Narimatsu, Satoshi Sakamoto, Yasuo Izumi, Masanori Abe, Hiroshi Handa

    CHEMISTRY LETTERS   35 ( 8 )   974 - 975   2006.8

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    DOI： 10.1246/cl.2006.974

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  • A formal total synthesis of (+)-pinnatoxin A Reviewed

    S Sakamoto, H Sakazaki, K Hagiwara, K Kamada, K Ishii, T Noda, M Inoue, M Hirama

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   43 ( 47 )   6505 - 6510   2004

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    DOI： 10.1002/anie.200461802

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  • Construction of the AG-ring unit of pinnatoxin A via intramolecular alkylation and aza-Wittig reaction

    Jin Wang, Satoshi Sakamoto, Kei Kamada, Aiko Nitta, Takeshi Noda, Hiroki Oguri, Masahiro Hirama

    Synlett   ( 6 )   891 - 893   2003

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MISC

  • Development of magnet configurations for magnetic immunostaining (vol 8, 056732, 2018)

    Miki Kaneko, Shinichi Chikaki, Sachiko Matsuda, Akihiro Kuwahata, Masayuki Namita, Itsuro Saito, Satoshi Sakamoto, Hiroshi Handa, Moriaki Kusakabe, Masaki Sekino

    AIP ADVANCES   9 ( 9 )   2019.9

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  • Development of an automatic magnetic immunostaining system for rapid diagnosis of cancer metastasis

    2019 ( 40 )   7 - 10   2019.6

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  • 抗体標識化磁性ビーズを利用する高速・高感度生体分子検出システムの開発

    坂本聡, 加部泰明, 平井美和, 小池一康, 菱木貴子, 松田厚志, 長谷川祐一, 辻田公二, 小野雅之, 峯岸直子, 寳澤篤, 村上善則, 久保充明, 久保充明, 望月勇輔, 河田慎太郎, 内藤靖之, 松田祐子, 北川雄光, 糸長誠, 末松誠, 半田宏

    日本化学会春季年会講演予稿集(CD-ROM)   99th   ROMBUNNO.3F5‐03   2019.3

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  • MEDICAL ENGINEERING COLLABORATION IN THE FIELD OF BREAST SURGERY : IDENTIFICATION OF SENTINEL LYMPH NODES USING MAGNETIC NANOPARTICLES AND NEW IMMUNOSTAINING METHOD

    120 ( 1 )   137 - 139   2019

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  • ドーム型磁石を用いた磁気免疫染色における染色一様性の評価

    藤田 俊祐, 関野 正樹, 桑波田 晃弘, 金子 美樹, 隣 真一, 松田 祐子, 坂本 聡, 斎藤 逸郎, 半田 宏, 日下部 守昭

    生体医工学   57 ( 0 )   S157_2 - S157_2   2019

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    <p>磁石と抗体標識蛍光磁気ビーズを用いた磁気免疫染色法は、ビーズに内包されたフェライトを磁石により磁化し、組織切片上に素早く引き付けることで、抗原抗体反応を促進し、がん抗原の検出をわずか数分で可能とする。正確な診断を短時間で行うためには均一かつ強力な磁力によって、ビーズを空間的一様に組織切片へと引き付ける必要がある。本研究では、磁気免疫染色法においてドーム型形状の磁石を用いることを提案し、磁気免疫染色実験を実施し染色効果の確認を行った。 磁気ビーズの運動を数値解析した結果、典型的な円柱磁石では磁石中央と磁石端でビーズに生じる磁力が不均一になるために、空間一様性の高い染色ができないことが明らかとなった。そこで、均一な磁力を発生させるドーム型磁石の設計と染色時間中の一様性の評価を実施し、直径30mmで高さ30mmの上面に曲率半径50mmの球面を有する磁石が最適であることを明らかとした。また、上皮成長因子受容体を高発現したヒト類表皮がん培養細胞の染色実験を実施し、ドーム型磁石は円柱磁石に比べて蛍光強度の変化の少ない空間一様性の高い染色が1分間で可能であることを示し、提案するドーム型磁石の有用性を明らかとした。</p>

    DOI： 10.11239/jsmbe.Annual57.S157_2

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  • Development of a rapid magnetic immunostaining method using antibody-labelled fluorescence magnetic beads

    SAKAMOTO Satoshi, MATSUDA Sachiko, TSURUMA Akinori, ONISHI Tatsuya, KUWAHATA Akihiro, SEKINO Masaki, KUSAKABE Moriaki, KITAGAWA Yuko, HANDA Hiroshi

    日本化学会春季年会講演予稿集(CD-ROM)   99th   2019

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  • Sentinel node navigation surgery using SPIO and magnetically-promoted rapid immunofluorescence staining

    2018 ( 204 )   55 - 57   2018.12

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  • Design of magnet shape and characterization by numerical analysis for magnetic immunostaining

    2018 ( 204 )   63 - 67   2018.12

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  • 蛍光磁性ビーズを利用した高速高感度免疫測定システムの開発

    田中 俊行, 畠山 士, 安野 寛, 羽生 尚広, 坂本 聡, 半田 宏

    Medical Science Digest   44 ( 8 )   449 - 452   2018.7

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  • 乳腺外科領域における医工連携 磁気ナノ粒子を用いたセンチネルリンパ節の同定と新たな免疫染色法

    武井 寛幸, 中村 清吾, 日下部 守昭, 関野 正樹, 中川 貴之, 半田 宏, 坂本 聡, 北川 雄光, 松田 香織, 栗田 智子, 垂野 香苗

    日本外科学会定期学術集会抄録集   118回   829 - 829   2018.4

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  • Analysis of magnetic force distribution of magnet array for magnetic immunostaining

    金子 美樹, 隣 真一, 松田 祐子, 桑波田 晃弘, 並田 将幸, 斉藤 逸郎, 坂本 聡, 日下部 守昭, 関野 正樹

    電気学会研究会資料. MAG = The papers of technical meeting on magnetics, IEE Japan   2018 ( 31 )   11 - 15   2018.3

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  • 抗体標識化蛍光磁性ビーズを利用する迅速疾患診断システムの開発

    坂本聡, 松田祐子, 日下部守昭, 関野正樹, 北川雄光, 半田宏

    日本化学会春季年会講演予稿集(CD-ROM)   98th   2018

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  • Convex magnet configuration for magnetic immunostaining

    KANEKO MIKI, KUWAHATA AKIHIRO, MATSUDA SACHIKO, CHIKAKI CHINICHI, NAMITA MASAYUKI, SAITO ITSURO, SAKAMOTO SATOSHI, KUSAKABE MORIAKI, SEKINO MASAKI

    Transactions of Japanese Society for Medical and Biological Engineering   56 ( 0 )   S402 - S402   2018

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    <p>Magnetic immunostaining can significantly promote the immunoreaction using a magnet and antibody-labeled fluorescent ferrite (FF) beads and diagnose the cancer metastasis during operation. We proposed a convex magnet for uniformly attracting antibody-labeled FF beads toward antigens on an entire tissue section and evaluated the magnet configuration by the curvature radius in the magnet surface. In numerical analysis result, the optimal curvature radius was 55 mm.</p>

    DOI： 10.11239/jsmbe.Annual56.S402

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  • 抗炎症薬サリチル酸が示す生体内作用メカニズムの解析

    坂本聡, VIPUL Gupta, LIU Shujie, 安藤秀樹, 舘野峻平, 金子裕生, 湯上真人, 石井亮平, 濡木理, 山口雄輝, 半田宏

    日本化学会春季年会講演予稿集(CD-ROM)   97th   2017

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  • 機能性磁性微粒子の計数を基盤とした高精度生体分子測定技術の開発

    坂本聡, 長谷川祐一, 辻田公二, 小野雅之, 加部泰明, 糸長誠, 半田宏

    日本化学会講演予稿集   95th ( 1 )   2015

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  • 標的同定とバリデーションの実際 半田ビーズを用いたサリドマイド標的同定

    坂本聡, 伊藤拓水, 半田宏

    CSJ Current Review   ( 19 )   2015

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  • 機能化された分散性微粒子を利用する生体分子測定技術の開発

    坂本聡, 長谷川祐一, 柳生慎悟, 辻田公二, 小野雅之, 加部泰明, 糸長誠, 半田宏

    日本化学会講演予稿集   94th ( 1 )   2014

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  • 新規蛍光・磁性ビーズを用いた迅速疾患診断 : 蛍光体と磁性体を内包したビーズを用いて病気の診断時間を1/10以下に短縮

    坂本 聡, 半田 宏

    光アライアンス   24 ( 2 )   56 - 60   2013.2

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  • 分散性磁気微粒子の高精度計数による生体分子検出技術の開発

    坂本聡, 辻田公二, 長谷川祐一, 小野雅之, 畠山士, 加部泰明, 糸長誠, 末松誠, 半田宏

    日本化学会講演予稿集   93rd ( 1 )   2013

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  • 光ディスク技術を応用したバイオマーカー高精度検出技術の開発

    小野雅之, 辻田公二, 長谷川祐一, 柳生慎悟, 糸長誠, 加部泰明, 坂本聡, 半田宏, 半田宏

    化学とマイクロ・ナノシステム学会研究会講演要旨集   27th   2013

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  • Innovative separation and purification technology of biomolecules by using affinity-magnetic beads

    畠山 士, 坂本 聡, Sandhu Adarsh

    Materials integration   23 ( 9 )   17 - 23   2010.9

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  • ついに解明! サリドマイドが起こす催奇性の謎--標的分子セレブロンを突き止めたFGビーズ

    伊藤 拓水, 坂本 聡, 半田 宏

    化学   65 ( 8 )   47 - 51   2010.8

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  • Detection of Magnetic Nanoparticles by Magnetically Mediated Self-Assembly of Superparamagnetic Microbeads

    MORIMOTO Yoshitaka, SAKAMOTO Satoshi, ABE Masanori, HANDA Hiroshi, SANDHU Adarsh

    Bulletin of Topical Symposium of the Magnetics Society of Japan   164   7 - 10   2009.2

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  • Observation of Binding Mode of a Sulfur-Containing Compound with Ferrite Nanoparticles

    Kosuke Nishio, Yoshinori Kita, Hiroshi Kishi, Yuka Masaike, Yuusuke Mochizuki, Kensuke Imai, Satoshi Sakamoto, Mamoru Hatakeyama, Yasuo Izumi, Masanori Abe, Hiroshi Handa

    Photon Factory Activity Report 2007   25B   56 - 56   2008

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  • 【絵で見てわかるナノDDS マテリアルから見た治療・診断・予後・予防、ヘルスケア技術の最先端】 金属 フェライト フェライトを利用したナノ磁性粒子のDDSへの応用

    坂本 聡, 畠山 士, 西尾 広介, 半田 宏

    遺伝子医学MOOK   別冊 ( 絵で見てわかるナノDDS )   192 - 199   2007.12

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  • Chemical Biology/Chemical Genetics Utilizing Affinity Nanobeads

    SAKAMOTO Satoshi, KABE Yasuaki, HANDA Hiroshi

    KAGAKU TO SEIBUTSU   45 ( 10 )   712 - 717   2007.10

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    DOI： 10.1271/kagakutoseibutsu1962.45.712

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  • アフィニティ精製用担体としての高分子微粒子

    畠山 士, 西尾 広介, 中村 光裕, 坂本 聡, 関口 健司, 羽生 尚広, 加部 泰明, 和田 忠士, 半田 宏

    Inflammation and Regeneration   27 ( 4 )   402 - 402   2007.7

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  • Preparation of size-controlled (30-100 nm) magnetite nanoparticles for biomedical applications

    K. Nishio, M. Ikeda, N. Gokon, S. Tsubouchi, H. Narimatsu, Y. Mochizuki, S. Sakamoto, A. Sandhu, M. Abe, H. Handa

    JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS   310 ( 2 )   2408 - 2410   2007.3

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  • 糖とアミノ酸からワクチンを : 合成化学による抗がん性ワクチンの開発(E・医療薬科学)

    坂本 聡

    ファルマシア   43 ( 3 )   253 - 254   2007

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    Language：Japanese   Publisher：公益社団法人 日本薬学会  

    DOI： 10.14894/faruawpsj.43.3_253

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  • タンパク質を操るビーズ技術 (特集 ケミカルバイオロジー--タンパク質機能を調節する小分子の世界)

    加部 泰明, 坂本 聡, 半田 宏

    バイオニクス   3 ( 10 )   32 - 38   2006.10

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  • 96(P-40) Synthetic Study of Pinnatoxin A

    Sakamoto Satoshi, Noda Takeshi, Hirama Masahiro

    Symposium on the Chemistry of Natural Products, symposium papers   44 ( 0 )   563 - 568   2002

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    Pinnatoxin A (1) was isolated by Uemura and co-workers from the Pinna muricata in 1995. While 1 is partly responsible for food poisoning in China and Japan, 1 shows significant Ca^<2+> channel activity. Structure of 1 features: 1) a spirocyclic imine (A-ring), 2) a bis-spiroacetal (BCD-ring), and 3) a 27-membered macrocarbocycle. We describe herein our progress toward the convergent total synthesis of 1. The macrocarbocycle 1 was divided into two fragments, the BCD-ring fragment 4 and the AEFG-ring fragment 5. After the two fragments are linked, the macrocarbocycle will be constructed by using RCM reaction. Starting from the allylic alcohol 8, ketone 10 was synthesized through consecutive asymmetric oxidations. By tratment 10 with CSA in MeOH and then changing the solvent to toluene, the desired bis-spiroacetal 11 was selectively obtained, which was then converted to 4. On the other hand, 5 was synthesized from the aldehyde 12, that was derived from D-glucose in 8 steps. Grignard reaction of 12 and 14 gave an alcohol in high yield, which was then converted to the nitrile 15. KN(TMS)_2 mediated cyclization of 15 successfully gave 16 as a single isomer. Manipulation of protecting groups and introduction of the methyl group at C27 as well as an allyl group afforded 5. Both fragments 4 and 5 in hand were linked using t-BuLi in the presence of HMPA. After selective desilylation, treatment of 22 with the highly active Grubbs catalyst 19 produced the desired 27-membered carbocycle 23 in high yield. Hydrolysis of the dithioacetal 23 followed by acid treatment with TFA in MeOH successfully formed the EF-ring. Introduction of the exo methylene (C10), ketone (C6) and azide groups (C1) gave the carboxylic acid 27. The total synthesis of 1 is actively under progress in our research group.

    DOI： 10.24496/tennenyuki.44.0_563

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Presentations

  • 天然物ケミカルバイオロジー 天然物ターゲットID最前線 アフィニティビーズを利用した生物活性物質標的タンパク質の単離・同定・評価

    坂本 聡, 山口 雄輝, 半田 宏

    日本薬学会年会要旨集  2015.3 

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  • 内分泌撹乱物質ビスフェノールAの生体内作用機構解析

    伊藤 雄気, 梨本 明宏, 羽瀬 康嘉, 坂本 聡, 加部 泰明, 半田 宏

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集  2010.12 

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    Language：Japanese  

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  • 抗炎症作用を有する12員環マクロライドの創製と標的タンパク質の探索

    菅原 章公, 廣瀬 友靖, 坂本 聡, 半田 宏, 大村 智, 砂塚 敏明

    日本薬学会年会要旨集  2016.3 

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  • 骨粗鬆症薬ビスフォスフォネート系化合物の標的タンパク質の解析

    坂本 聡, 政池 由佳, 廣田 雅隆, 山田 丈, 高木 毅, 石原 聡, 澤 智華, 加部 泰明, 相良 洋, 半田 宏

    日本生化学会大会プログラム・講演要旨集  2009.9 

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  • 96(P-40) Synthetic Study of Pinnatoxin A

    Sakamoto Satoshi, Noda Takeshi, Hirama Masahiro

    Symposium on the Chemistry of Natural Products, symposium papers  2002 

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    Language：Japanese  

    Pinnatoxin A (1) was isolated by Uemura and co-workers from the Pinna muricata in 1995. While 1 is partly responsible for food poisoning in China and Japan, 1 shows significant Ca^<2+> channel activity. Structure of 1 features: 1) a spirocyclic imine (A-ring), 2) a bis-spiroacetal (BCD-ring), and 3) a 27-membered macrocarbocycle. We describe herein our progress toward the convergent total synthesis of 1. The macrocarbocycle 1 was divided into two fragments, the BCD-ring fragment 4 and the AEFG-ring fragment 5. After the two fragments are linked, the macrocarbocycle will be constructed by using RCM reaction. Starting from the allylic alcohol 8, ketone 10 was synthesized through consecutive asymmetric oxidations. By tratment 10 with CSA in MeOH and then changing the solvent to toluene, the desired bis-spiroacetal 11 was selectively obtained, which was then converted to 4. On the other hand, 5 was synthesized from the aldehyde 12, that was derived from D-glucose in 8 steps. Grignard reaction of 12 and 14 gave an alcohol in high yield, which was then converted to the nitrile 15. KN(TMS)_2 mediated cyclization of 15 successfully gave 16 as a single isomer. Manipulation of protecting groups and introduction of the methyl group at C27 as well as an allyl group afforded 5. Both fragments 4 and 5 in hand were linked using t-BuLi in the presence of HMPA. After selective desilylation, treatment of 22 with the highly active Grubbs catalyst 19 produced the desired 27-membered carbocycle 23 in high yield. Hydrolysis of the dithioacetal 23 followed by acid treatment with TFA in MeOH successfully formed the EF-ring. Introduction of the exo methylene (C10), ketone (C6) and azide groups (C1) gave the carboxylic acid 27. The total synthesis of 1 is actively under progress in our research group.

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Research Projects

  • 細胞外dATPマクロファージに対する貪食・細胞障害性機序の解析

    Grant number：17K00882  2017.4 - 2020.3

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

    澤 智華, 坂本 聡, 井上 由理子

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

    近年炎症細胞や好中球などの壊死やアポトーシスで放出された核酸の機能が注目されてきている。我々はこれまでに細胞外核酸は直接がん細胞に作用し細胞増殖抑制を示し、dATPのみマクロファージ様細胞株に作用してIL-8やTHBS1(Thrombospondin 1)など様々な因子の発現を誘導誘導し、細胞障害性を持つことをin vitroで報告した。
    そこで本研究では細胞外核酸、特にdATPによるマクロファージの活性化に注目し、創傷治癒効果の可能性を検討すること目的とした。IL-8は好中球やNK・T細胞の走化性を誘導し、初期免疫応答に重要な役割を担っている。またTHBS-1は血管新生抑制と酸化ストレスを誘導し、止血誘導や細胞増殖障害性が見られることがIn vitroで報告されている。そのため本研究ではこれらの予備データを基に、ネオジウム磁石を用いた創傷モデルマウスを作成し、核酸を創傷部位に局所投与することを試みた。壊死した細胞や好中球から放出された核酸が近傍のマクロファージに作用し、THBS1が発現誘導することをin vitroで確認し、早期の創傷治癒及び肥厚性瘢痕の抑制効果を比較検討している。

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