松原 輝彦 (マツバラ テルヒコ)

Matsubara, Teruhiko

写真a

所属(所属キャンパス)

理工学部 生命情報学科 (矢上)

職名

准教授

HP

外部リンク

総合紹介 【 表示 / 非表示

  • オリゴ糖鎖が関わる疾患の早期発見や治療に有用な生体ナノ分子を創成し、ウイルスを高感度検出するバイオセンサーや感染阻害剤などを開発している。また非接触および無容器で反応が可能な音響浮揚による次世代のケミカルバイオロジー研究を展開している。

経歴 【 表示 / 非表示

  • 1999年01月
    -
    2000年06月

    日本学術振興会 特別研究員

  • 2000年07月
    -
    2003年03月

    徳島大学工学部 助手

  • 2003年04月
    -
    2007年03月

    大学助手(理工学部生命情報学科)

  • 2007年04月
    -
    2008年03月

    大学助教(職位変更による)(理工学部生命情報学科)

  • 2008年04月
    -
    2019年03月

    大学専任講師(理工学部生命情報学科)

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学歴 【 表示 / 非表示

  • 1995年03月

    岡山大学, 工学部, 生体機能応用工学科

    大学, 卒業

  • 1997年03月

    岡山大学, 工学研究科, 生体機能応用工学専攻

    大学院, 修了, 修士

  • 2000年03月

    東京工業大学, 生命理工学研究科, バイオテクノロジー専攻

    大学院, 修了, 博士

学位 【 表示 / 非表示

  • 博士(工学), 東京工業大学, 課程, 2000年03月

 

研究分野 【 表示 / 非表示

  • ナノテク・材料 / 生体化学 (Chemistry Related to Living Body)

研究キーワード 【 表示 / 非表示

  • ガングリオシド

  • ファージディスプレイ

  • ペプチドライブラリー

  • 複合糖質

  • 音響浮揚

共同研究希望テーマ 【 表示 / 非表示

  • オリゴ糖鎖のクラスターに結合する分子の利用

    産学連携、民間を含む他機関等との共同研究等を希望する,  希望形態: 受託研究, 共同研究, その他

  • ファージ提示法による標的分子および物質に対するランダムライブラリーからのペプチドおよびタンパク質の選択

    大学等の研究機関との共同研究を希望する

 

著書 【 表示 / 非表示

  • Influenza Virus

    Matsubara T., Sato T., Diamond Electrodes Fundamentals and Applications, 2022年01月

     概要を見る

    The rapid diagnosis of patients in clinical practice is important for anti-influenza therapy. However, since the sensitivity of conventional rapid diagnostic test kits is low, false-negative results are often produced. Therefore, simple and convenient test kits with high sensitivity are needed in clinical practice. In this chapter, we describe the construction of a boron-doped diamond (BDD) electrode that terminates with a receptor (sialic acid-containing oligosaccharide chain)-mimicking peptide as well as its performance in the electrochemical detection of human and avian influenza viruses (IFVs).

  • ペプチド医薬品のスクリーニング・安定化・製剤化技術

    110名, 技術情報協会, 2017年12月

    担当範囲: 6章1節

  • 生体分子化学-基礎から応用まで

    杉本 直己, 内藤 昌信, 橋詰 峰雄, 高橋 俊太郎, 田中 直毅, 建石 寿枝, 遠藤 玉樹, 津本 浩平, 長門石 曉, 松原 輝彦, 上田 実, 朝山 章一郎, 講談社サイエンティフィク, 2017年01月

    担当範囲: 9章(p197-224)

  • 超分子サイエンス&テクノロジー

    松原 輝彦・佐藤智典, NTS, 2009年05月

    担当範囲: 1036-1042

  • Contemporary Trends in Bacteriophage Research

    MATSUBARA TERUHIKO, Nova Science Publishers, Inc., 2009年05月

    担当範囲: 407-419

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論文 【 表示 / 非表示

  • Prevention of amyloid β fibril deposition on the synaptic membrane in the precuneus by ganglioside nanocluster-targeting inhibitors

    Miyamoto E., Hayashi H., Murayama S., Yanagisawa K., Sato T., Matsubara T.

    Rsc Chemical Biology 5 ( 5 ) 459 - 466 2024年04月

     概要を見る

    Alzheimer's disease (AD), a progressive neurodegenerative condition, is one of the most common causes of dementia. Senile plaques, a hallmark of AD, are formed by the accumulation of amyloid β protein (Aβ), which starts to aggregate before the onset of the disease. Gangliosides, sialic acid-containing glycosphingolipids, play a key role in the formation of toxic Aβ aggregates. In membrane rafts, ganglioside-bound complexes (GAβ) act as nuclei for Aβ assembly, suggesting that GAβ is a promising target for AD therapy. The formation of GAβ-induced Aβ assemblies has been evaluated using reconstituted planar lipid membranes composed of synaptosomal plasma membrane (SPM) lipids extracted from human and mouse brains. Although the effects of gangliosides on Aβ accumulation in the precuneus have been established, effects on Aβ fibrils have not been determined. In this study, Aβ<inf>42</inf> fibrils on reconstituted membranes composed of SPM lipids prepared from the precuneus cortex of human autopsied brains were evaluated by atomic force microscopy. In particular, Aβ<inf>42</inf> accumulation, as well as the fibril number and size were higher for membranes with precuneus lipids than for membranes with calcarine cortex lipids. In addition, artificial peptide inhibitors targeting Aβ-sensitive ganglioside nanoclusters cleared Aβ assemblies on synaptic membranes in the brain, providing a novel therapeutic strategy for AD.

  • Cyclization of Peptides Enhances the Inhibitory Activity against Ganglioside-Induced Aβ Fibril Formation

    Miyamoto E., Sato T., Matsubara T.

    ACS Chemical Neuroscience 14 ( 23 ) 4199 - 4207 2023年12月

     概要を見る

    Alzheimer’s disease is a progressive neurodegenerative disease and is the most common cause of dementia. It has been reported that the assembly of amyloid β-protein (Aβ) on the cell membrane is induced by the interaction of the Aβ monomer with gangliosides such as GM1. The ganglioside-bound Aβ (GAβ) complex acts as a seed to promote the toxic assembly of the Aβ fibrils. In a previous study, we found that a GM1 cluster-binding peptide (GCBP) specifically recognizes Aβ-sensitive ganglioside nanoclusters and inhibits the assembly of Aβ on a GM1-containing lipid membrane. In this study, cysteine-substituted double mutants of GCBP were designed and cyclized by intramolecular disulfide bond formation. Affinity assays indicated that one of the cyclic peptides had a higher affinity to a GM1-containing membrane compared to that of GCBP. Furthermore, surface topography analysis indicated that this peptide recognizes GM1 nanoclusters on the lipid membrane. An evaluation of the inhibitory kinetics indicated that the cyclic peptide could inhibit the formation of Aβ fibrils with an IC<inf>50</inf> value of 1.2 fM, which is 10,000-fold higher than that of GCBP. The cyclic peptide was also shown to have a clearance effect on Aβ fibrils deposited on the lipid membrane and suppressed the formation of toxic Aβ assemblies. Our results indicate that the cyclic peptide that binds to the Aβ-sensitive ganglioside nanocluster is a potential novel inhibitor of ganglioside-induced Aβ assembly.

  • Effects of the Magnetic Orientation of M13 Bacteriophage on Phage Display Selection

    Wang S., Uchida N., Ueno K., Matsubara T., Sato T., Aida T., Ishida Y.

    Chemistry A European Journal 29 ( 63 )  2023年11月

    ISSN  09476539

     概要を見る

    Although phage display selection using a library of M13 bacteriophage has become a powerful tool for finding peptides that bind to target materials on demand, a remaining concern of this method is the interference by the M13 main body, which is a huge filament >10<sup>3</sup> times larger than the displayed peptide, and therefore would nonspecifically adhere to the target or sterically inhibit the binding of the displayed peptide. Meanwhile, filamentous phages are known to be orientable by an external magnetic field. If M13 filaments are magnetically oriented during the library selection, their angular arrangement relative to the target surface would be changed, being expected to control the interference by the M13 main body. This study reports that the magnetic orientation of M13 filaments vertical to the target surface significantly affects the selection. When the target surface was affinitive to the M13 main body, this orientation notably suppressed the nonspecific adhesion. Furthermore, when the target surface was less affinitive to the M13 main body and intrinsically free from the nonspecific adhesion, this orientation drastically changed the population of M13 clones obtained through library selection. The method of using no chemicals but only a physical stimulus is simple, clean, and expected to expand the scope of phage display selection.

  • Endocytosis-Like Vesicle Fission Mediated by a Membrane-Expanding Molecular Machine Enables Virus Encapsulation for In Vivo Delivery

    Uchida N., Ryu Y., Takagi Y., Yoshizawa K., Suzuki K., Anraku Y., Ajioka I., Shimokawa N., Takagi M., Hoshino N., Akutagawa T., Matsubara T., Sato T., Higuchi Y., Ito H., Morita M., Muraoka T.

    Journal of the American Chemical Society 145 ( 11 ) 6210 - 6220 2023年03月

    ISSN  00027863

     概要を見る

    Biological membranes are functionalized by membrane-associated protein machinery. Membrane-associated transport processes, such as endocytosis, represent a fundamental and universal function mediated by membrane-deforming protein machines, by which small biomolecules and even micrometer-size substances can be transported via encapsulation into membrane vesicles. Although synthetic molecules that induce dynamic membrane deformation have been reported, a molecular approach enabling membrane transport in which membrane deformation is coupled with substance binding and transport remains critically lacking. Here, we developed an amphiphilic molecular machine containing a photoresponsive diazocine core (AzoMEx) that localizes in a phospholipid membrane. Upon photoirradiation, AzoMEx expands the liposomal membrane to bias vesicles toward outside-in fission in the membrane deformation process. Cargo components, including micrometer-size M13 bacteriophages that interact with AzoMEx, are efficiently incorporated into the vesicles through the outside-in fission. Encapsulated M13 bacteriophages are transiently protected from the external environment and therefore retain biological activity during distribution throughout the body via the blood following administration. This research developed a molecular approach using synthetic molecular machinery for membrane functionalization to transport micrometer-size substances and objects via vesicle encapsulation. The molecular design demonstrated in this study to expand the membrane for deformation and binding to a cargo component can lead to the development of drug delivery materials and chemical tools for controlling cellular activities.

  • Dihydromaniwamycin E, a Heat-Shock Metabolite from Thermotolerant Streptomyces sp. JA74, Exhibiting Antiviral Activity against Influenza and SARS-CoV-2 Viruses

    Saito S., Funayama K., Kato W., Okuda M., Kawamoto M., Matsubara T., Sato T., Sato A., Otsuguro S., Sasaki M., Orba Y., Sawa H., Maenaka K., Shindo K., Imoto M., Arai M.A.

    Journal of Natural Products 85 ( 11 ) 2583 - 2591 2022年11月

    ISSN  01633864

     概要を見る

    Dihydromaniwamycin E (1), a new maniwamycin derivative featuring an azoxy moiety, has been isolated from the culture extract of thermotolerant Streptomyces sp. JA74 along with the known analogue maniwamycin E (2). Compound 1 is produced only by cultivation of strain JA74 at 45 °C, and this type of compound has been previously designated a "heat shock metabolite (HSM)" by our research group. Compound 2 is detected as a production-enhanced metabolite at high temperature. Structures of 1 and 2 are elucidated by NMR and MS spectroscopic analyses. The absolute structure of 1 is determined after the total synthesis of four stereoisomers. Though the absolute structure of 2 has been proposed to be the same as the structure of maniwamycin D, the NMR and the optical rotation value of 2 are in agreement with those of maniwamycin E. Therefore, this study proposes a structural revision of maniwamycins D and E. Compounds 1 and 2 show inhibitory activity against the influenza (H1N1) virus infection of MDCK cells, demonstrating IC<inf>50</inf>values of 25.7 and 63.2 μM, respectively. Notably, 1 and 2 display antiviral activity against SARS-CoV-2, the causative agent of COVID-19, when used to infect 293TA and VeroE6T cells, with 1 and 2 showing IC<inf>50</inf>values (for infection of 293TA cells) of 19.7 and 9.7 μM, respectively. The two compounds do not exhibit cytotoxicity in these cell lines at those IC<inf>50</inf>concentrations.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

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競争的研究費の研究課題 【 表示 / 非表示

  • 音響浮揚現象を活用した細胞への高効率遺伝子導入法の開発

    2024年06月
    -
    2026年03月

    松原 輝彦, 挑戦的研究(萌芽), 補助金,  研究代表者

  • ファージ提示法で得られたペプチド配列リソースの標的指向型修飾法の開発

    2023年04月
    -
    2025年03月

    松原 輝彦, 学術変革領域研究(A), 補助金,  研究代表者

  • 全方位非接触界面による革新的バイオリアクターの開発

    2020年07月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 松原 輝彦, 挑戦的研究(萌芽), 補助金,  研究代表者

  • 難合成糖鎖受容体を分子模倣した修飾ペプチドの活性機構解明

    2015年04月
    -
    2018年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 松原 輝彦, 基盤研究(C), 補助金,  研究代表者

受賞 【 表示 / 非表示

  • 東京糖鎖研究会(GlycoTOKYO)奨励賞

    松原 輝彦, 2010年11月, 東京糖鎖研究会(GlycoTOKYO), ライブラリーを用いた糖鎖-タンパク質間相互作用を制御するペプチドの設計

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • 若い世代の特別講演会(第23回)講演証

    松原 輝彦, 2009年03月, 日本化学会第89春季年会2009, ライブラリー選択法で得られた新規ペプチドによる細胞表面糖鎖の機能制御

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • バイオ関連化学合同シンポジウム講演賞

    松原 輝彦, 2006年09月, バイオ関連化学合同シンポジウム(日本化学会生体関連化学部会、バイオテクノロジー部会、生命化学研究会), ヘマグルチニン糖鎖結合ポケットを認識するペプチド分子設計

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • ISBC 2003 Poster Award

    松原 輝彦, 2003年12月, First International Symposium on Biomolecular Chemistry, Functions of carbohydrate-binding peptides selected from phage-displayed peptide library

    受賞区分: 国内学会・会議・シンポジウム等の賞

     説明を見る

    First International Symposium on Biomolecular Chemistry (ISBC 2003), December 4, 2003

 

担当授業科目 【 表示 / 非表示

  • 生命情報特別講義第1

    2025年度

  • 生命情報輪講

    2025年度

  • 現代生物学概論

    2025年度

  • 生物学序論

    2025年度

  • 基礎理工学課題研究

    2025年度

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所属学協会 【 表示 / 非表示

  • 日本ペプチド学会, 

    2021年04月
    -
    継続中
  • 日本ソノケミストリー学会, 

    2020年04月
    -
    継続中
  • 日本神経化学会, 

    2017年04月
    -
    継続中
  • 日本糖質学会, 

    2004年10月
    -
    継続中
  • 遺伝子・デリバリー研究会, 

    2003年04月
    -
    継続中

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委員歴 【 表示 / 非表示

  • 2011年01月
    -
    継続中

    ASSOCIATE EDITOR, Trends in Glycoscience and Glycotechnology

  • 2011年01月
    -
    2017年12月

    Financial Secretary, FCCA