研究者データベース

村岡 貴博MURAOKA Takahiroムラオカ タカヒロ

所属部署名工学研究院 応用化学部門
職名教授
Last Updated :2025/09/09

業績情報

氏名・連絡先

  • 氏名

    ムラオカ タカヒロ, 村岡 貴博, MURAOKA Takahiro
  • eメールアドレス

    muraokago.tuat.ac.jp
  • 個人ホームページ

    https://www.muraoka-lab.com

主たる所属・職名

  • 工学研究院 応用化学部門, 教授

その他の所属

  • グローバルイノベーション研究院テニュアトラック推進機構
  • 工学研究院

経歴

  • 東京工業大学
    生命理工学院
    助教
    自 2015年05月01日, 至 2017年01月31日
  • 科学技術振興機構
    戦略的創造推進事業さきがけ「分子技術と新機能創出」領域
    さきがけ研究者
    自 2013年10月01日, 至 2017年03月31日
  • 東北大学
    多元物質科学研究所
    助教
    自 2008年05月01日, 至 2015年04月30日
  • 日本学術振興会
    特別研究員 (PD)
    自 2007年04月01日, 至 2008年04月30日
  • ノースウェスタン大学
    化学科
    訪問研究員
    自 2006年07月06日, 至 2008年04月30日
  • 日本学術振興会
    特別研究員 (DC1)
    自 2004年04月01日, 至 2007年03月31日

学歴

  • 東京大学
    工学系研究科
    化学生命工学専攻
    至 2007年03月31日, 修了, 博士後期
  • 東京大学
    工学系研究科
    化学生命工学専攻
    至 2004年03月31日, 修了, 博士前期
  • 東京大学
    工学部
    化学生命工学科
    至 2002年03月31日, 卒業

教育・研究活動状況

  • 分子の集合体を構築し、機能制御する学問を超分子化学と言います。「生体は究極の分子集合体である」という点に着目し、当研究室では有機合成と超分子化学を基盤として、タンパク質や細胞などの生体の活動を操作する新材料開発を行っています。

研究分野

  • A489 ナノテク・材料, A37010 生体化学

研究キーワード

  • 有機合成
  • 超分子化学
  • タンパク質フォールディング
  • 光応答性物質
  • 両親媒性物質
  • リポソーム
  • イオンチャネル
  • 分子機械
  • ペプチド

科学研究費助成事業

  • 国際共同研究加速基金(海外連携研究)
    分泌経路におけるメゾスケール構造体プロファイリングの開拓
    自 2024年, 至 2024年
  • 国際共同研究加速基金(海外連携研究)
    分泌経路におけるメゾスケール構造体プロファイリングの開拓
    自 2023年, 至 2023年
  • 挑戦的研究(萌芽)
    高生産性細菌創製に向けた膜透過性ペプチドを基盤とした革新的な形質転換技術の開発
    自 2022年, 至 2022年
  • 新学術領域研究(研究領域提案型)
    物質輸送光発動分子システムの構築と応用
    自 2021年, 至 2021年
  • 学術変革領域研究(B)(総括班)
    遅延制御超分子化学の推進
    自 2021年, 至 2023年
  • 学術変革領域研究(B)(計画研究)
    遅延制御機能を示す人工分子の開発と非対称構造構築への実証
    自 2021年, 至 2023年
  • 挑戦的研究(萌芽)
    光トランスフェクション法の開発
    自 2021年, 至 2023年
  • 挑戦的研究(萌芽)
    高生産性細菌創製に向けた膜透過性ペプチドを基盤とした革新的な形質転換技術の開発
    自 2021年, 至 2021年
  • 基盤研究(B)
    タンパク質模倣に基づく酸化的フォールディング促進剤の開発
    自 2019年, 至 2021年
  • 若手研究(A)
    動的多次元場を構築する機能性分子開発
    自 2017年, 至 2018年
  • 新学術領域研究(研究領域提案型)
    多様な刺激に応答するπ組織体の応用
    自 2017年, 至 2018年

論文

  • Ligand Design with Accelerated Disulfide Formation with Serum Albumin to Extend Blood Retention
    Qi, Song; Liu, Zixuan; Suyama, Keitaro; Tsuchiya, Yuichi; Jedidiah, Canarejo; Phan, Khanh Quoc; Yutsudo, Noriko; Shimada, Atsushi; Hirota, Takeshi; Ieiri, Ichiro; Kishimura, Akihiro; Muraoka, Takahiro; Nose, Takeru; Mori, Takeshi; Katayama, Yoshiki
    ACS MEDICINAL CHEMISTRY LETTERS
    AMER CHEMICAL SOC
    We proposed a novel ligand for the interaction with human serum albumin (HSA) to extend the blood half-life of small molecular weight therapeutics. The ligand features an alkyl chain and an activated disulfide to allow binding to the hydrophobic pockets of HSA and the formation of disulfide to Cys34 of HSA, thereby minimizing the initial renal clearance. The dual nature of the ligand-HSA bonding was expected to give the ligand long blood retention. After 1 min of mixing with HSA, the ligand showed higher binding (1.7 times) than that of a control ligand (containing only activated disulfide). After intravenous injection to mice, the ligand half-lives were 1.6 and 9.2 times longer than those of control ligands with the active disulfide alone and with the alkyl chain alone, respectively. The proposed ligand has the potential to act as a platform for extending the half-life of small therapeutics in vivo.
    2024年12月16日, 研究論文(学術雑誌), 共同, 16, 1, 1948-5875, DOI(公開)(r-map), 144, 148
  • Redox-active chemical chaperones exhibiting promiscuous binding promote oxidative protein folding under condensed sub-millimolar conditions
    Suzuki, Koki; Nojiri, Ryoya; Matsusaki, Motonori; Mabuchi, Takuya; Kanemura, Shingo; Ishii, Kotone; Kumeta, Hiroyuki; Okumura, Masaki; Saio, Tomohide; Muraoka, Takahiro
    CHEMICAL SCIENCE
    ROYAL SOC CHEMISTRY
    Proteins form native structures through folding processes, many of which proceed through intramolecular hydrophobic effect, hydrogen bond and disulfide-bond formation. In vivo, protein aggregation is prevented even in the highly condensed milieu of a cell through folding mediated by molecular chaperones and oxidative enzymes. Chemical approaches to date have not replicated such exquisite mediation. Oxidoreductases efficiently promote folding by the cooperative effects of oxidative reactivity for disulfide-bond formation in the client unfolded protein and chaperone activity to mitigate aggregation. Conventional synthetic folding promotors mimic the redox-reactivity of thiol/disulfide units but do not address client-recognition units for inhibiting aggregation. Herein, we report thiol/disulfide compounds containing client-recognition units, which act as synthetic oxidoreductase-mimics. For example, compound beta CDWSH/SS bears a thiol/disulfide unit at the wide rim of beta-cyclodextrin as a client recognition unit. beta CDWSH/SS shows promiscuous binding to client proteins, mitigates protein aggregation, and accelerates disulfide-bond formation. In contrast, positioning a thiol/disulfide unit at the narrow rim of beta-cyclodextrin promotes folding less effectively through preferential interactions at specific residues, resulting in aggregation. The combination of promiscuous client-binding and redox reactivity is effective for the design of synthetic folding promoters. beta CDWSH/SS accelerates oxidative protein folding at highly condensed sub-millimolar protein concentrations. A promiscuous protein binder with redox activity efficiently promotes oxidative protein folding under condensed sub-millimolar conditions.
    2024年08月14日, 研究論文(学術雑誌), 共同, 15, 32, 2041-6520, DOI(公開)(r-map)
  • Boosting the enzymatic activity of CxxC motif-containing PDI family members
    Kuramochi, Tsubura; Yamashita, Yukino; Arai, Kenta; Kanemura, Shingo; Muraoka, Takahiro; Okumura, Masaki
    CHEMICAL COMMUNICATIONS
    ROYAL SOC CHEMISTRY
    Compounds harboring high acidity and oxidizability of thiol groups permit tuning the redox equilibrium constants of CxxC sites of members of the protein disulphide isomerase (PDI) family and thus can be used to accelerate folding processes and increase the production of native proteins by minimal loading in comparison to glutathione. Compounds harboring high acidity and oxidizability of thiol groups permit tuning the redox equilibrium constants of CxxC sites of the PDI family enzymes and thus can be used to promote oxidative folding and increase the native protein productions by minimal loading as compared to glutathione.
    2024年06月11日, 研究論文(学術雑誌), 共同, 60, 48, 1359-7345, DOI(公開)(r-map)
  • ROS-Responsive Methionine-Containing Amphiphilic Peptides Impart Enzyme-Triggered Phase Transition and Antioxidant Cell Protection
    Hara, Yoshika; Yoshizawa, Ken; Yaguchi, Atsuya; Hiramatsu, Hirotsugu; Uchida, Noriyuki; Muraoka, Takahiro
    BIOMACROMOLECULES
    AMER CHEMICAL SOC
    Reactive oxygen species (ROS) are produced by cellular activities, such as metabolism and immune response, and play important roles in cell signaling and homeostasis. However, overproduced ROS causes irreversible damage to nucleic acids and membrane lipids, supporting genetic mutations and enhancing the effects of aging. Cells defend themselves against ROS using antioxidant systems based on redox-active sulfur and transition metals. Inspired by such biological redox-responsive systems, we developed methionine-containing self-assembling peptides. The Met-containing peptides formed hydrogels that underwent a gel-to-sol phase transition upon oxidation by H2O2, and the sensitivity of the peptides to the oxidant increased as the number of Met residues increased. The peptide containing three Met residues, the largest number of Met residues in our series of designed peptides, showed the highest sensitivity to oxidation and detoxification to protect cells from ROS damage. In addition, this peptide underwent a phase transition in response to H2O2 produced by an oxidizing enzyme. This study demonstrates the design of a supramolecular biomaterial that is responsive to enzymatically generated ROS and can protect cells against oxidative stress.
    2024年05月09日, 研究論文(学術雑誌), 共同, 25, 6, 1525-7797, DOI(公開)(r-map), 3499, 3506
  • Activator of KAT3 histone acetyltransferase family ameliorates a neurodevelopmental disorder phenotype in the syntaxin 1A ablated mouse model
    Nakayama, Takahiro; Singh, Akash K.; Fukutomi, Toshiyuki; Uchida, Noriyuki; Terao, Yasuo; Hamada, Hiroki; Muraoka, Takahiro; Muthusamy, Eswaramoorthy; Kundu, Tapas K.; Akagawa, Kimio
    CELL REPORTS
    CELL PRESS
    Syntaxin-1A ( stx1a ) repression causes a neurodevelopmental disorder phenotype, low latent inhibition (LI) behavior, by disrupting 5-hydroxytryptaminergic (5-HTergic) systems. Herein, we discovered that lysine acetyltransferase (KAT) 3B increases stx1a neuronal transcription and TTK21, a KAT3 activator, induces stx1a transcription and 5 -HT release in vitro . Furthermore, glucose -derived CSP-TTK21 could restore decreased stx1a expression, 5-HTergic systems in the brain, and low LI in stx1a (+/ - ) mice by crossing the blood -brain barrier, whereas the KAT3 inhibitor suppresses stx1a expression, 5-HTergic systems, and LI behaviors in wild -type mice. Finally, in wild -type and stx1a ( - / - ) mice treated with IKK inhibitors and CSP-TTK21, respectively, we show that KAT3 activator -induced LI improvement is a direct consequence of KAT3B- stx1a pathway, not a side effect. In conclusion, KAT3B can positively regulate stx1a transcription in neurons, and increasing neuronal stx1a expression and 5-HTergic systems by a KAT3 activator consequently improves the low LI behavior in the stx1a ablation mouse model.
    2024年04月23日, 研究論文(学術雑誌), 共同, 43, 4, 2211-1247, DOI(公開)(r-map)
  • Rapid Synthesis of Chiral Figure-Eight Macrocycles Using a Preorganized Natural Product-Based Scaffold
    Honda, Tasuku; Ogata, Daiji; Tsurui, Makoto; Yoshida, Satoshi; Sato, Sota; Muraoka, Takahiro; Kitagawa, Yuichi; Hasegawa, Yasuchika; Yuasa, Junpei; Oguri, Hiroki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
    WILEY-V C H VERLAG GMBH
    Chiral D2-symmetric figure-eight shaped macrocycles are promising scaffolds for amplifying the chiroptical properties of pi-conjugated systems. By harnessing the inherent and adaptable conformational dynamics of a chiral C2-symmetric bispyrrolidinoindoline (BPI) manifold, we developed an enantio-divergent modular synthetic platform to rapidly generate a diverse range of chiral macrocycles, spanning from 14- to 66-membered rings, eliminating the need for optical resolution. Notably, a 32-membered figure-eight macrocycle showed excellent circularly polarized luminescence (CPL: |glum|=1.1x10-2) complemented by a robust emission quantum yield (phi fl=0.74), to achieve outstanding CPL brightness (BCPL: epsilon x phi flx|glum|/2=480). Using quadruple Sonogashira couplings, this versatile synthetic platform enables precise adjustments of the angle, distance, and length among intersecting pi-conjugated chromophores. Our synthetic strategy offers a streamlined and systematic approach to significantly enhance BCPL values for a variety of chiral D2-symmetric figure-eight macrocycles. A chiral D2-symmetric Figure-eight macrocycle, which exhibits bright CPL (glum=0.011, phi fl=0.74, BCPL=480), was efficiently synthesized using a versatile C2-symmetric natural product-based manifold with a preorganized conformation. This rapid and modular synthetic platform allows flexible and precise tuning of the angle, distance, and length among intersecting pi-conjugated chromophores in shape-persistent figure-eight macrocycles.image
    2024年02月26日, 研究論文(学術雑誌), 共同, 63, 9, 1433-7851, DOI(公開)(r-map)
  • Enzymatic and synthetic regulation of polypeptide folding
    Muraoka, Takahiro; Okumura, Masaki; Saio, Tomohide
    CHEMICAL SCIENCE
    ROYAL SOC CHEMISTRY
    Proper folding is essential for the biological functions of all proteins. The folding process is intrinsically error-prone, and the misfolding of a polypeptide chain can cause the formation of toxic aggregates related to pathological outcomes such as neurodegenerative disease and diabetes. Chaperones and some enzymes are involved in the cellular proteostasis systems that assist polypeptide folding to diminish the risk of aggregation. Elucidating the molecular mechanisms of chaperones and related enzymes is important for understanding proteostasis systems and protein misfolding- and aggregation-related pathophysiology. Furthermore, mechanistic studies of chaperones and related enzymes provide important clues to designing chemical mimics, or chemical chaperones, that are potentially useful for recovering proteostasis activities as therapeutic approaches for treating and preventing protein misfolding-related diseases. In this Perspective, we provide a comprehensive overview of the latest understanding of the folding-promotion mechanisms by chaperones and oxidoreductases and recent progress in the development of chemical mimics that possess activities comparable to enzymes, followed by a discussion of future directions. This perspective focuses on the latest understanding of the folding-promotion mechanisms by chaperones and oxidoreductases and recent progress in the development of chemical mimics that possess activities comparable to enzymes.
    2024年02月14日, 研究論文(学術雑誌), 共同, 15, 7, 2041-6520, DOI(公開)(r-map)
  • Self-assembling materials functionalizing bio-interfaces of phospholipid membranes and extracellular matrices
    Uchida, Noriyuki; Muraoka, Takahiro
    CHEMICAL COMMUNICATIONS
    ROYAL SOC CHEMISTRY
    This Feature Article focuses on recent studies on the development of self-assembling materials that mimic and control dynamic bio-interfaces. Extracellular matrix (ECM) is a fundamental tissue at the cellular interface constructed by networks of fibrous proteins, which regulates a variety of cellular activities. Reconstruction of ECM has been demonstrated by self-assembling peptides. By combining the dynamic properties of the self-assembling peptides conjugated with full-length proteins, peptide-based supramolecular materials enable neuronal migration and regeneration of injured neural tissue. The phospholipid bilayer is the main component of the cell membrane. The morphology and deformation of the phospholipid bilayer relate directly to dynamic interfacial functions. Stabilization of the phospholipid nanosheet structure has been demonstrated by self-assembling peptides, and the stabilized bicelle is functional for extended blood circulation. By using a photo-responsive synthetic surfactant showing a mechanical opening/closing motion, endocytosis-like outside-in membrane deformation is triggered. The outside-in deformation allows for efficient encapsulation of micrometer-size substances such as phage viruses into the liposomes, and the encapsulated viruses can be delivered to multiple organs in a living body via blood administration. These supramolecular approaches to mimicking and controlling bio-interfaces present powerful ways to develop unprecedented regenerative medicines and drug delivery systems.
    2023年08月08日, 研究論文(学術雑誌), 共同, 59, 64, 1359-7345, DOI(公開)(r-map), 9687, 9697
  • Semi-enzymatic acceleration of oxidative protein folding by N-methylated heteroaromatic thiols
    Okada, Shunsuke; Matsumoto, Yosuke; Takahashi, Rikana; Arai, Kenta; Kanemura, Shingo; Okumura, Masaki; Muraoka, Takahiro
    CHEMICAL SCIENCE
    ROYAL SOC CHEMISTRY
    We report the first example of a synthetic thiol-based compound that promotes oxidative protein folding upon 1-equivalent loading to the disulfide bonds in the client protein to afford the native form in over 70% yield. N-Methylation is a central post-translational processing of proteins in vivo for regulating functions including chaperone activities. Despite the universally observed biochemical reactions in nature, N-methylation has hardly been utilized in the design, functionalization, and switching of synthetic bioregulatory agents, particularly folding promotors. As a biomimetic approach, we developed pyridinylmethanethiols to investigate the effects of N-methylation on the promotion of oxidative protein folding. For a comprehensive study on the geometrical effects, constitutional isomers of pyridinylmethanethiols with ortho-, meta-, and para-substitutions have been synthesized. Among the constitutional isomers, para-substituted pyridinylmethanethiol showed the fastest disulfide-bond formation of the client proteins to afford the native forms most efficiently. N-Methylation drastically increased the acidity and enhanced the oxidizability of the thiol groups in the pyridinylmethanethiols to enhance the folding promotion efficiencies. Among the isomers, para-substituted N-methylated pyridinylmethanethiol accelerated the oxidative protein folding reactions with the highest efficiency, allowing for protein folding promotion by 1-equivalent loading as a semi-enzymatic activity. This study will offer a novel bioinspired molecular design of synthetic biofunctional agents that are semi-enzymatically effective for the promotion of oxidative protein folding including biopharmaceuticals such as insulin in vitro by minimum loading.
    2023年07月19日, 研究論文(学術雑誌), 共同, 14, 28, 2041-6520, DOI(公開)(r-map), 7630, 7636
  • ROS-Triggered Gel-Sol Transition and Kinetics-Controlled Cargo Release by Methionine-Containing Peptides
    Hara, Yoshika; Yaguchi, Atsuya; Hiramatsu, Hirotsugu; Muraoka, Takahiro
    CHEMBIOCHEM
    WILEY-V C H VERLAG GMBH
    The gel-sol transition of self-assembling peptides is a useful switch for environment-dependent drug release. For their applications, kinetics control of the responses is important for matching the velocity of release to the target biological events. Here we demonstrate the chemical control of redox-triggered gel-sol transition kinetics of self-assembling peptides by altering the amino acid sequence. Amphiphilic peptides were developed in which a methionine residue was located in the middle (JigSAP-IMI) or near the N terminus (JigSAP-MII). Both peptides formed hydrogels under physiological conditions-forming beta-sheet-based supramolecular nanofibers. In contrast, the oxidized forms remained in the solution state under identical conditions-adopting alpha-helix-rich secondary structures. Upon oxidation with H2O2, a reactive oxygen species, JigSAP-MII showed a faster gel-to-sol transition and cargo-releasing than JigSAP-IMI, thus indicating that the phase-transition and releasing kinetics of self-assembling peptides can be rationally controlled by the position of the reactive amino acid residue.
    2023年05月02日, 研究論文(学術雑誌), 共同, 24, 9, 1439-4227, DOI(公開)(r-map)
  • Endocytosis-Like Vesicle Fission Mediated by a Membrane- Expanding Molecular Machine Enables Virus Encapsulation for In Vivo Delivery
    Uchida, Noriyuki; Ryu, Yunosuke; Takagi, Yuichiro; Yoshizawa, Ken; Suzuki, Kotono; Anraku, Yasutaka; Ajioka, Itsuki; Shimokawa, Naofumi; Takagi, Masahiro; Hoshino, Norihisa; Akutagawa, Tomoyuki; Matsubara, Teruhiko; Sato, Toshinori; Higuchi, Yuji; Ito, Hiroaki; Morita, Masamune; Muraoka, Takahiro
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
    AMER CHEMICAL SOC
    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.
    2023年03月22日, 研究論文(学術雑誌), 共同, 145, 11, 0002-7863, DOI(公開)(r-map), 6210, 6220
  • Amphiphilic peptide-tagged N-cadherin forms radial glial-like fibers that enhance neuronal migration in injured brain and promote sensorimotor recovery
    Ohno, Yuya; Nakajima, Chikako; Ajioka, Itsuki; Muraoka, Takahiro; Yaguchi, Atsuya; Fujioka, Teppei; Akimoto, Saori; Matsuo, Misaki; Lotfy, Ahmed; Nakamura, Sayuri; Herranz-Perez, Vicente; Manuel Garcia-Verdugo, Jose; Matsukawa, Noriyuki; Kaneko, Naoko; Sawamoto, Kazunobu
    BIOMATERIALS
    ELSEVIER SCI LTD
    The mammalian brain has very limited ability to regenerate lost neurons and recover function after injury. Promoting the migration of young neurons (neuroblasts) derived from endogenous neural stem cells using biomaterials is a new and promising approach to aid recovery of the brain after injury. However, the delivery of sufficient neuroblasts to distant injured sites is a major challenge because of the limited number of scaffold cells that are available to guide neuroblast migration. To address this issue, we have developed an amphiphilic peptide [(RADA)3-(RADG)] (mRADA)-tagged N-cadherin extracellular domain (Ncad-mRADA), which can remain in mRADA hydrogels and be injected into deep brain tissue to facilitate neuroblast migration. Migrating neuroblasts directly contacted the fiber-like Ncad-mRADA hydrogel and efficiently migrated toward an injured site in the striatum, a deep brain area. Furthermore, application of Ncad-mRADA to neonatal cortical brain injury efficiently promoted neuronal regeneration and functional recovery. These results demonstrate that selfassembling Ncad-mRADA peptides mimic both the function and structure of endogenous scaffold cells and provide a novel strategy for regenerative therapy.
    2023年03月, 研究論文(学術雑誌), 共同, 294, 0142-9612, DOI(公開)(r-map)
  • Oxidative Protein Folding Promotion by Imidazoyl-conjugated Thiol
    Okada, Shunsuke; Matsumoto, Yosuke; Okumura, Masaki; Muraoka, Takahiro
    CHEMISTRY LETTERS
    CHEMICAL SOC JAPAN
    The promotion of protein folding is an important subject that can contribute to the efficient production of biological medicines. Here we report the promotion of disulfide bond-coupled protein folding by imidazoyl-conjugated thiol (ImdSH). ImdSH accelerated the disulfide bond formation and folding of reduced ribonuclease A and bovine pancreatic trypsin inhibitor relative to glutathione as a conventionally used additive.
    2023年03月, 研究論文(学術雑誌), 共同, 52, 3, 0366-7022, DOI(公開)(r-map), 202, 205
  • Coacervate Formation of Elastin-like Polypeptides in Explicit Aqueous Solution Using Coarse-Grained Molecular Dynamics Simulations
    Mabuchi, Takuya; Kijima, Junko; Yamashita, Yukino; Miura, Erika; Muraoka, Takahiro
    MACROMOLECULES
    AMER CHEMICAL SOC
    We performed coarse-grained molecular dynamics simulations with the Martini3 force field to investigate elastin-like polypeptide (ELP) coacervate formation and its internal structural and dynamics properties. Coacervate formation was found to be enhanced with increasing polymer concentration and polymer length, whereas no significant changes in the structural and dynamic properties inside the coacervate phase were observed among coacervates with different polymer concentrations and polymer lengths. The ion and water concentrations as well as the diffusion coefficients of water inside a coacervate were found to be reduced compared with that in bulk water. In addition, ELP phase separation behaviors were also observed experimentally and the trend of ELP concentration/length-dependent formation of a coacervate in the simulations was found to be in qualitative agreement with our experimental observations. Furthermore, simulations of the partitioning of RNA polymers demonstrate that an RNA polymer with ethyl (hydrophobic) modification favors the inside of a coacervate and shows a larger radius of gyration in comparison with a normal RNA polymer without modification (negatively charged). Our simulations provide a means to explore the requirement for control over coacervate formation and stability in a wide range of conditions. Understanding how specific sequence and structural features affect coacervate morphology and stability could help in the design of new biopolymers with additional desirable properties. [GRAPHICS]
    2023年02月14日, 研究論文(学術雑誌), 共同, 56, 3, 0024-9297, DOI(公開)(r-map), 794, 805
  • Self-assembling Materials Functionalizing Bio-interfaces of Phospholipid Membranes and Extracellular Matrices
    Noriyuki Uchida and Takahiro Muraoka
    Chemical Communications
    2023年, 研究論文(学術雑誌), 共同, 59, DOI(公開)(r-map), 9687, 9697
  • Semi-Enzymatic Acceleration of Oxidative Protein Folding by N-Methylated Heteroaromatic Thiols
    Shunsuke Okada, Yosuke Matsumoto, Rikana Takahashi, Kenta Arai, Shingo Kanemura, Masaki Okumura and Takahiro Muraoka
    Chemical Science
    2023年, 研究論文(学術雑誌), 共同, 14, DOI(公開)(r-map), 7630, 7636
  • Endocytosis-Like Vesicle Fission Mediated by a Membrane-Expanding Molecular Machine Enables Virus Encapsulation for In Vivo Delivery
    Noriyuki Uchida, Yunosuke Ryu, Yuichiro Takagi, Ken Yoshizawa, Kotono Suzuki, Yasutaka Anraku, Itsuki Ajioka, Naofumi Shimokawa, Masahiro Takagi, Norihisa Hoshino, Tomoyuki Akutagawa, Teruhiko Matsubara, Toshinori Sato, Yuji Higuchi, Hiroaki Ito, Masamune Morita and Takahiro Muraoka
    Journal of the American Chemical Society
    2023年, 研究論文(学術雑誌), 共同, 145, DOI(公開)(r-map), 6210, 6220
  • ROS-Triggered Gel–Sol Transition and Kinetics-Controlled Cargo Release by Methionine-Containing Peptides
    Yoshika Hara, Atsuya Yaguchi, Hirotsugu Hiramatsu and Takahiro Muraoka
    ChemBioChem
    2023年, 研究論文(学術雑誌), 共同, 24, DOI(公開)(r-map), e202200798
  • Coacervate Formation of Elastin-like Polypeptides in Explicit Aqueous Solution Using Coarse-Grained Molecular Dynamics Simulations
    Takuya Mabuchi, Junko Kijima, Yukino Yamashita, Erika Miura and Takahiro Muraoka
    Macromolecules
    2023年, 研究論文(学術雑誌), 共同, 56, DOI(公開)(r-map), 794, 805
  • Cell-Penetrating Peptide-Peptide Nucleic Acid Conjugates as a Tool for Protein Functional Elucidation in the Native Bacterium
    Yokoi, Yasuhito; Kawabuchi, Yugo; Zulmajdi, Abdullah Adham; Tanaka, Reiji; Shibata, Toshiyuki; Muraoka, Takahiro; Mori, Tetsushi
    MOLECULES
    MDPI
    Approximately 30% or more of the total proteins annotated from sequenced bacteria genomes are annotated as hypothetical or uncharacterized proteins. However, elucidation on the function of these proteins is hindered by the lack of simple and rapid screening methods, particularly with novel or hard-to-transform bacteria. In this report, we employed cell-penetrating peptide (CPP) -peptide nucleotide acid (PNA) conjugates to elucidate the function of such uncharacterized proteins in vivo within the native bacterium. Paenibacillus, a hard-to-transform bacterial genus, was used as a model. Two hypothetical genes showing amino acid sequence similarity to iota-carrageenases, termed cgiA and cgiB, were identified from the draft genome of Paenibacillus sp. strain YYML68, and CPP-PNA probes targeting the mRNA of the acyl carrier protein gene, acpP, and the two iota-carrageenase candidate genes were synthesized. Upon direct incubation of CPP-PNA targeting the mRNA of the acpP gene, we successfully observed growth inhibition of strain YYML68 in a concentration-dependent manner. Similarly, both the function of the candidate iota-carrageenases were also inhibited using our CPP-PNA probes allowing for the confirmation and characterization of these hypothetical proteins. In summary, we believe that CPP-PNA conjugates can serve as a simple and efficient alternative approach to characterize proteins in the native bacterium.
    2022年12月, 研究論文(学術雑誌), 共同, 27, 24, DOI(公開)(r-map)
  • Cysteine-based protein folding modulators for trapping intermediates and misfolded forms
    Nishino, Hayato; Kitamura, Mai; Okada, Shunsuke; Miyake, Ryosuke; Okumura, Masaki; Muraoka, Takahiro
    RSC ADVANCES
    ROYAL SOC CHEMISTRY
    Folding is a key process to form functional conformations of proteins. Folding via on-pathway intermediates leads to the formation of native structures, while folding through off-pathways affords non-native and disease-causing forms. Trapping folding intermediates and misfolded forms is important for investigating folding mechanisms and disease-related biological properties of the misfolded proteins. We developed cysteine-containing dipeptides conjugated with amino acids possessing mono- and diamino-groups. In oxidative protein folding involving disulfide-bond formation, the addition of cysteine and oxidized glutathione readily promoted the folding to afford native forms. In contrast, despite the acceleration of disulfide-bond formation, non-native isomers formed in significantly increased yields upon the addition of the dipeptides. This study provides a molecular design of cysteine-based protein-folding modulators that afford proteins adopting non-native conformations through intermolecular disulfide-bond formation. Because of the intrinsic reversibility of the disulfide bonds upon redox reactions, the disulfide bond-based approach demonstrated here is expected to lead to the development of reversible methodologies for trapping transient and misfolded forms by intermolecular disulfide bond formation and restarting the folding processes of the trapped forms by subsequent cleavage of the intermolecular disulfide bonds.
    2022年09月16日, 研究論文(学術雑誌), 共同, 12, 41, DOI(公開)(r-map), 26658, 26664
  • Self-assembling Molecular Medicine for the Subacute Phase of Ischemic Stroke
    Muraoka, Takahiro; Ajioka, Itsuki
    NEUROCHEMICAL RESEARCH
    SPRINGER/PLENUM PUBLISHERS
    Ischemic stroke leads to acute neuron death and forms an injured core, triggering delayed cell death at the penumbra. The impaired brain functions after ischemic stroke are hardly recovered because of the limited regenerative properties. However, recent rodent intervention studies manipulating the extracellular environments at the subacute phase shed new light on the regenerative potency of the injured brain. This review introduces the rational design of artificial extracellular matrix (ECM) mimics using supramolecular peptidic scaffolds, which self-assemble via non-covalent bonds and form hydrogels. The facile customizability of the peptide structures allows tuning the hydrogels' physical and biochemical properties, such as charge states, hydrophobicity, cell adhesiveness, stiffness, and stimuli responses. Supramolecular peptidic materials can create safer and more economical drugs than polymer materials and cell transplantation. We also discuss the importance of activating developmental programs for the recovery at the subacute phase of ischemic stroke. Self-assembling molecular medicine mimicking the ECMs and activating developmental programs may stand as a new drug modality of regenerative medicine in various tissues.
    2022年09月, 研究論文(学術雑誌), 共同, 47, 9, 0364-3190, DOI(公開)(r-map), 2488, 2498
  • Jigsaw-shaped self-assembling peptide (JigSAP) hydrogels efficiently incorporate and release VEGF and promote brain regeneration
    Ajioka, Itsuki; Yaguchi, Atsuya; Oshikawa, Mio; Watanabe, Go; Muraoka, Takahiro
    JOURNAL OF NEUROCHEMISTRY
    WILEY
    2022年08月, 研究論文(国際会議プロシーディングス), 共同, 162, 0022-3042, DOI(公開)(r-map), 104, 104
  • Stabilization of bicelles using metal-binding peptide for extended blood circulation
    Takagi, Yuichiro; Uchida, Noriyuki; Anraku, Yasutaka; Muraoka, Takahiro
    CHEMICAL COMMUNICATIONS
    ROYAL SOC CHEMISTRY
    A metal-binding peptide appending cholic acid, Chol-MBP, formed bicelles by mixing with 1,2-dipalmitoyl-sn-glycero-3-phosphorylcholine (DPPC). Coordination of Chol-MBP with Cu2+ stabilized DPPC bicelles against dilution and contamination of serum proteins, enabling extended blood circulation. This study demonstrates an effective supramolecular design of phospholipid bicelles with enhanced stability useful for membrane-based biomaterials.
    2022年04月21日, 研究論文(学術雑誌), 共同, 58, 33, 1359-7345, DOI(公開)(r-map), 5164, 5167
  • 生体模倣から開発する蛋白質安定化低分子
    村岡貴博
    アグリバイオ
    2022年02月03日, (MISC)総説・解説(商業誌), 単独, 6, 2, 78, 80
  • Efficient protein incorporation and release by a jigsaw-shaped self-assembling peptide hydrogel for injured brain regeneration
    Yaguchi, Atsuya; Oshikawa, Mio; Watanabe, Go; Hiramatsu, Hirotsugu; Uchida, Noriyuki; Hara, Chikako; Kaneko, Naoko; Sawamoto, Kazunobu; Muraoka, Takahiro; Ajioka, Itsuki
    NATURE COMMUNICATIONS
    NATURE PORTFOLIO
    The extracellular matrix contributes to tissue regeneration by binding and releasing growth factors. Here the authors present the jigsaw-shaped self-assembling peptide JigSAP as an artificial ECM and show that VEGF-JigSAP has therapeutic effects on the subacute-chronic phase of brain stroke. During injured tissue regeneration, the extracellular matrix plays a key role in controlling and coordinating various cellular events by binding and releasing secreted proteins in addition to promoting cell adhesion. Herein, we develop a cell-adhesive fiber-forming peptide that mimics the jigsaw-shaped hydrophobic surface in the dovetail-packing motif of glycophorin A as an artificial extracellular matrix for regenerative therapy. We show that the jigsaw-shaped self-assembling peptide forms several-micrometer-long supramolecular nanofibers through a helix-to-strand transition to afford a hydrogel under physiological conditions and disperses homogeneously in the hydrogel. The molecular- and macro-scale supramolecular properties of the jigsaw-shaped self-assembling peptide hydrogel allow efficient incorporation and sustained release of vascular endothelial growth factor, and demonstrate cell transplantation-free regenerative therapeutic effects in a subacute-chronic phase mouse stroke model. This research highlights a therapeutic strategy for injured tissue regeneration using the jigsaw-shaped self-assembling peptide supramolecular hydrogel.
    2021年11月19日, 研究論文(学術雑誌), 共同, 12, 1, DOI(公開)(r-map)
  • Supramolecular Transmembrane Ion Channels Formed by Multiblock Amphiphiles
    Sato, Kohei; Muraoka, Takahiro; Kinbara, Kazushi
    ACCOUNTS OF CHEMICAL RESEARCH
    AMER CHEMICAL SOC
    CONSPECTUS: Transmembrane proteins located within biological membranes play a crucial role in a variety of important cellular processes, such as energy conversion and signal transduction. Among them, ion channel proteins that can transport specific ions across the biological membranes are particularly important for achieving precise control over those processes. Strikingly, approximately 20% of currently approved drugs are targeted to ion channel proteins within membranes. Thus, synthetic molecules that can mimic the functions of natural ion channel proteins would possess great potential in the sensing and manipulation of biologically important processes, as well as in the purification of key industrial materials. Inspired by the sophisticated structures and functions of natural ion channel proteins, our research group developed a series of multiblock amphiphiles (MAs) composed of a repetitive sequence of flexible hydrophilic oligo(ethylene glycol) chains and rigid hydrophobic oligo(phenylene-ethynylene) units. These MAs can be effectively incorporated into the hydrophobic layer of lipid bilayer membranes and adopt folded conformations, with their hydrophobic units stacked in a face-to-face configuration. Moreover, the folded MAs can self-assemble within the membranes and form supramolecular nanopores that can transport ions across the membranes. In these studies, we focused on the structural flexibility of the MAs and decided to design new molecules able to respond to various external stimuli in order to control their transmembrane ion transport properties. For this purpose, we developed new MAs incorporating sterically bulky groups within their hydrophobic units and demonstrated that their transmembrane ion transport properties could be controlled via mechanical forces applied to the membranes. Moreover, we developed MAs incorporating phosphate ester groups that functioned as ligand-binding sites at the boundary between hydrophilic and hydrophobic units and found that these MAs exhibited transmembrane ion transport properties upon binding with aromatic amine ligands, even within the biological membranes of living cells. We further modified the hydrophobic units of the MAs with fluorine atoms and demonstrated their voltage-responsive transmembrane ion transport properties. These molecular design principles were extended to the development of a transmembrane anion transporter whose transport mechanism was studied by all-atom molecular dynamics simulations. This Account describes the basic principles of the molecular designs of MAs, the characterization of their self-assembled structures within a lipid bilayer, and their transmembrane ion transport properties, including their responsiveness to stimuli. Finally, we discuss future perspectives on the manipulation of biological processes based on the characteristic features of MAs.
    2021年10月05日, 研究論文(学術雑誌), 共同, 54, 19, 0001-4842, DOI(公開)(r-map), 3700, 3709
  • 生体模倣から開発する蛋白質安定化低分子
    村岡貴博
    月刊「細胞」
    2021年08月24日, (MISC)総説・解説(商業誌), 単独, 53, 9, 57, 58
  • Hydrogel-Stiffening and Non-Cell Adhesive Properties of Amphiphilic Peptides with Central Alkylene Chains
    Yaguchi, Atsuya; Hiramatsu, Hirotsugu; Ishida, Atsuya; Oshikawa, Mio; Ajioka, Itsuki; Muraoka, Takahiro
    CHEMISTRY-A EUROPEAN JOURNAL
    WILEY-V C H VERLAG GMBH
    Amphiphilic peptides bearing terminal alkyl tails form supramolecular nanofibers that are increasingly used as biomaterials with multiple functionalities. Insertion of alkylene chains in peptides can be designed as another type of amphiphilic peptide, yet the influence of the internal alkylene chains on self-assembly and biological properties remains poorly defined. Unlike the terminal alkyl tails, the internal alkylene chains can affect not only the hydrophobicity but also the flexibility and packing of the peptides. Herein, we demonstrate the supramolecular and biological effects of the central alkylene chain length inserted in a peptide. Insertion of the alkylene chain at the center of the peptide allowed for strengthened beta-sheet hydrogen bonds and modulation of the packing order, and consequently the amphiphilic peptide bearing C2 alkylene chain formed a hydrogel with the highest stiffness. Interestingly, the amphiphilic peptides bearing internal alkylene chains longer than C2 showed a diminished cell-adhesive property. This study offers a novel molecular design to tune mechanical and biological properties of peptide materials.
    2021年06月25日, 研究論文(学術雑誌), 共同, 27, 36, 0947-6539, DOI(公開)(r-map), 9295, 9301
  • Conjugate of Thiol and Guanidyl Units with Oligoethylene Glycol Linkage for Manipulation of Oxidative Protein Folding
    Okada, Shunsuke; Matsusaki, Motonori; Okumura, Masaki; Muraoka, Takahiro
    MOLECULES
    MDPI
    Oxidative protein folding is a biological process to obtain a native conformation of a protein through disulfide-bond formation between cysteine residues. In a cell, disulfide-catalysts such as protein disulfide isomerase promote the oxidative protein folding. Inspired by the active sites of the disulfide-catalysts, synthetic redox-active thiol compounds have been developed, which have shown significant promotion of the folding processes. In our previous study, coupling effects of a thiol group and guanidyl unit on the folding promotion were reported. Herein, we investigated the influences of a spacer between the thiol group and guanidyl unit. A conjugate between thiol and guanidyl units with a diethylene glycol spacer (GdnDEG-SH) showed lower folding promotion effect compared to the thiol-guanidyl conjugate without the spacer (GdnSH). Lower acidity and a more reductive property of the thiol group of GdnDEG-SH compared to those of GdnSH likely resulted in the reduced efficiency of the folding promotion. Thus, the spacer between the thiol and guanidyl groups is critical for the promotion of oxidative protein folding.
    2021年02月, 研究論文(学術雑誌), 共同, 26, 4, DOI(公開)(r-map)
  • Current Progress in Cross-Linked Peptide Self-Assemblies
    Uchida, Noriyuki; Muraoka, Takahiro
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    MDPI
    Peptide-based fibrous supramolecular assemblies represent an emerging class of biomaterials that can realize various bioactivities and structures. Recently, a variety of peptide fibers with attractive functions have been designed together with the discovery of many peptide-based self-assembly units. Cross-linking of the peptide fibers is a key strategy to improve the functions of these materials. The cross-linking of peptide fibers forming three-dimensional networks in a dispersion can lead to changes in physical and chemical properties. Hydrogelation is a typical change caused by cross-linking, which makes it applicable to biomaterials such as cell scaffold materials. Cross-linking methods, which have been conventionally developed using water-soluble covalent polymers, are also useful in supramolecular peptide fibers. In the case of peptide fibers, unique cross-linking strategies can be designed by taking advantage of the functions of amino acids. This review focuses on the current progress in the design of cross-linked peptide fibers and their applications.
    2020年10月, 研究論文(学術雑誌), 共同, 21, 20, DOI(公開)(r-map)
  • Reversible formation of multiple stimuli-responsive polymeric materials through processing control of trifunctional amphiphilic molecules
    Muraoka, Takahiro; Honda, Hidetaka; Nabeya, Kota; Kinbara, Kazushi
    CHEMICAL COMMUNICATIONS
    ROYAL SOC CHEMISTRY
    A nonionic amphiphile consisting of thermo-responsive tetraethylene glycol chains, redox-responsive thiol groups, and photo-responsive anthracene units was developed. By combining the thermal and redox stimuli in water and bulk to control the assembling processes, two pairs of polymeric materials possessing contrasting responses to thermal treatment and photoirradiation were prepared.
    2020年07月21日, 研究論文(学術雑誌), 共同, 56, 57, 1359-7345, DOI(公開)(r-map), 7881, 7884
  • Thermo-driven self-assembly of a PEG-containing amphiphile in a bilayer membrane
    Li, Rui; Muraoka, Takahiro; Kinbara, Kazushi
    RSC ADVANCES
    ROYAL SOC CHEMISTRY
    Self-assembly of lipid molecules in a plasma membrane, namely lipid raft formation, is involved in various dynamic functions of cells. Inspired by the raft formation observed in the cells, here we studied thermally induced self-assembly of a synthetic amphiphile,bola-AkDPA, in a bilayer membrane. The synthetic amphiphile consists of a hydrophobic unit including fluorescent aromatic and aliphatic components and hydrophilic tetraethylene glycol chains attached at both ends of the hydrophobic unit. In a polar solvent,bola-AkDPAformed aggregates to show excimer emission. In a lipid bilayer membrane,bola-AkDPAshowed intensified excimer emission upon increase of its concentration or elevation of the temperature; bola-type amphiphiles containing oligoethylene glycol chains likely tend to form self-assemblies in a bilayer membrane triggered by thermal stimuli.
    2020年07月08日, 研究論文(学術雑誌), 共同, 10, 43, DOI(公開)(r-map), 25758, 25762
  • A synthetic ion channel with anisotropic ligand response
    Muraoka, Takahiro; Noguchi, Daiki; Kasai, Rinshi S.; Sato, Kohei; Sasaki, Ryo; Tabata, Kazuhito V.; Ekimoto, Toru; Ikeguchi, Mitsunori; Kamagata, Kiyoto; Hoshino, Norihisa; Noji, Hiroyuki; Akutagawa, Tomoyuki; Ichimura, Kazuaki; Kinbara, Kazushi
    NATURE COMMUNICATIONS
    NATURE PUBLISHING GROUP
    Biological membranes play pivotal roles in the cellular activities. Transmembrane proteins are the central molecules that conduct membrane-mediated biochemical functions such as signal transduction and substance transportation. Not only the molecular functions but also the supramolecular properties of the transmembrane proteins such as self-assembly, delocalization, orientation and signal response are essential for controlling cellular activities. Here we report anisotropic ligand responses of a synthetic multipass transmembrane ion channel. An unsymmetrical molecular structure allows for oriented insertion of the synthetic amphiphile to a bilayer by addition to a pre-formed membrane. Complexation with a ligand prompts ion transportation by forming a supramolecular channel, and removal of the ligand deactivates the transportation function. Biomimetic regulation of the synthetic channel by agonistic and antagonistic ligands is also demonstrated not only in an artificial membrane but also in a biological membrane of a living cell.
    2020年06月10日, 研究論文(学術雑誌), 共同, 11, 1, 2041-1723, DOI(公開)(r-map)
  • New Modified Deoxythymine with Dibranched Tetraethylene Glycol Stabilizes G-Quadruplex Structures
    Tateishi-Karimata, Hisae; Ohyama, Tatsuya; Muraoka, Takahiro; Tanaka, Shigenori; Kinbara, Kazushi; Sugimoto, Naoki
    MOLECULES
    MDPI
    Methods for stabilizing G-quadruplex formation is a promising therapeutic approach for cancer treatment and other biomedical applications because stable G-quadruplexes efficiently inhibit biological reactions. Oligo and polyethylene glycols are promising biocompatible compounds, and we have shown that linear oligoethylene glycols can stabilize G-quadruplexes. Here, we developed a new modified deoxythymine with dibranched or tribranched tetraethylene glycol (TEG) and incorporated these TEG-modified deoxythymines into a loop region that forms an antiparallel G-quadruplex. We analyzed the stability of the modified G-quadruplexes, and the results showed that the tribranched TEG destabilized G-quadruplexes through entropic contributions, likely through steric hindrance. Interestingly, the dibranched TEG modification increased G-quadruplex stability relative to the unmodified DNA structures due to favorable enthalpic contributions. Molecular dynamics calculations suggested that dibranched TEG interacts with the G-quadruplex through hydrogen bonding and CH-pi interactions. Moreover, these branched TEG-modified deoxythymine protected the DNA oligonucleotides from degradation by various nucleases in human serum. By taking advantage of the unique interactions between DNA and branched TEG, advanced DNA materials can be developed that affect the regulation of DNA structure.
    2020年02月01日, 研究論文(学術雑誌), 共同, 25, 3, DOI(公開)(r-map)
  • Biofunctional Molecules Inspired by Protein Mimicry and Manipulation
    Muraoka, Takahiro
    BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
    CHEMICAL SOC JAPAN
    This account focuses on synthetic approaches to develop functional molecules on the basis of mimicry and manipulation of proteins. Proteins are one of the central molecules serving vital functions and maintaining biological homeostasis. The sophisticated roles and dynamic functions found in proteins provide lots of useful clues to develop synthetic functional molecules. This account describes the development of synthetic supramolecular ion channels made of multiblock structures that can switch ion transportation in response to external stimuli by mimicking ligand-gated and mechano-responsive transmembrane proteins. Multiblock amphiphiles also perform membrane budding and self-assembly in a bilayer. This account also describes functionalization of poly(ethylene glycol) by structuring, which allows for controlling the thermal properties and protein aggregation suppression. The thermal response of poly(ethylene glycol) is also effective in a solid state to develop crystals showing thermal polymorphic transitions.
    2020年01月, 研究論文(学術雑誌), 単独, 93, 1, 0009-2673, DOI(公開)(r-map), 138, 153
  • Abiotic Factors Promote Cell Penetrating Peptide Permeability in Enterobacteriaceae Models
    Toyohara, Daichi; Yokoi, Yasuhito; Inoue, Go; Muraoka, Takahiro; Mori, Tetsushi
    FRONTIERS IN MICROBIOLOGY
    FRONTIERS MEDIA SA
    Conventionally, the delivery of biomolecules into bacteria for the generation of characterized or functional mutants has relied greatly on horizontal gene transfer techniques. However, the low compatibility of these techniques with novel or hard-to-transform bacteria currently serves as a challenge to the bioengineering field. Here, we explored the use of cell penetrating peptides (CPPs) as an alternative biomolecule delivery approach by investigating the effects of the abiotic factors during CPP permeation. Using the (KFF)(3)K-FAM conjugate and Escherichia coli as models, we evaluated four abiotic factors where two of these factors, temperature and solution tonicity, promoted (KFF)(3)K-FAM permeation efficiency. Our data show that optimal (KFF)(3)K-FAM permeation efficiency was achieved for E. coli at approximately 98.1% under conditions of 37 degrees C (growth optimal temperature) and 50% PBS concentration. Based on these conditions, we subsequently tested the applicability of CPP permeation in various bacterial strains by treating 10 bacterial strains from the Enterobacteriaceae family among which seven strains have no CPP permeation records with (KFF)(3)K-FAM. Interestingly, when compared with non-optimized conditions, all 10 strains showed a marked increase in CPP permeation ranging between 20 and 90% efficiency. Although using strains within Enterobacteriaceae that are phylogenetically close, our results hinted on the possibility that with proper optimization of the abiotic factors, CPPs could be compatible with a broad range of bacterial strains. Our efforts suggest that CPP could serve as an effective alternative approach for mutant generation and for biomolecule delivery into novel or hard-to-transform bacteria.
    2019年11月26日, 研究論文(学術雑誌), 共同, 10, 1664-302X, DOI(公開)(r-map)
  • Glycine Substitution Effects on the Supramolecular Morphology and Rigidity of Cell-Adhesive Amphiphilic Peptides
    Ishida, Atsuya; Watanabe, Go; Oshikawa, Mio; Ajioka, Itsuki; Muraok, Takahiro
    CHEMISTRY-A EUROPEAN JOURNAL
    WILEY-V C H VERLAG GMBH
    Self-assembling peptides that are capable of adopting beta-sheet structures can generate nanofibers that lead to hydrogel formation. Herein, to tune the supramolecular morphologies, mechanical properties, and stimuli responses of the hydrogels, we investigated glycine substitution in a beta-sheet-forming amphiphilic peptide. Glycine substitution generally enhances conformational flexibility. Indeed, glycine substitution in an amphiphilic peptide weakened the hydrogels or even inhibited the gelation. However, unexpectedly, glycine substitution at the center of the peptide molecule significantly enhanced the hydrogel stiffness. The central glycine substitution affected the molecular packing and led to twisted beta-sheet structures and to nanofiber bundling, which likely led to the stiffened hydrogel. Importantly, the supramolecular structures were accurately predicted by molecular dynamics simulations, demonstrating the helpfulness of these techniques for the identification of self-assembling peptides. The hydrogel formed by the amphiphilic peptide with the central glycine substitution had cell adhesive function, and showed a reversible thermal gel-to-sol transition. Thus, glycine substitution is effective in modulating self-assembling structures, rheological properties, and dynamics of biofunctional self-assembling peptides.
    2019年10月22日, 研究論文(学術雑誌), 共同, 25, 59, 0947-6539, DOI(公開)(r-map), 13523, 13530
  • Formation of Giant and Small Cyclic Complexes from a Flexible Tripeptide Ligand Controlled by Metal Coordination and Hydrogen Bonds
    Miyake, Ryosuke; Ando, Akira; Ueno, Manami; Muraoka, Takahiro
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
    AMER CHEMICAL SOC
    Formation of giant cyclic complexes by the assembly of small, flexible units is demonstrated by connecting 14 artificial tripeptides (1) with 14 Ni(II) ions. Although tripeptide 1 is very flexible because of the presence of three CH2 groups in the main chain, it formed a tetradecanuclear cyclic complex [1(14)Ni(14)](28+)) with a large cavity (diameter: ca. 2 nm). In this structure, three tripeptides are coordinated to each Ni(II) center by three different coordination sites in 1, forming a mesh-like structure. Crystal structure analysis and theoretical calculations indicate that the conformation of 1 was controlled by the formation of metal coordination bonds and intramolecular hydrogen bonds. Because of the structural flexibility, the cyclic framework formed both circular and ellipsoidal structures in the crystalline state, depending on the packing structure. In addition, by the conditions of the assembly process, the size of the cavities could be tuned either with a small decrement (dodecanuclear complex [1(12)Ni(12)](24+),) or a large decrement (octanuclear complexes [(1-3H(+))(4)Ni-8](4+)), in which ”shrunk” cavities with a 10-fold difference in diameter (<0.2 nm) were formed by tuning the tripeptide conformation through additional metal coordination to the tripeptide framework. Dynamic light scattering and mass spectrometry studies indicated that the giant cyclic complexes were also present in the solution state.
    2019年06月05日, 研究論文(学術雑誌), 共同, 141, 22, 0002-7863, DOI(公開)(r-map), 8675, 8679
  • Coupling effects of thiol and urea-type groups for promotion of oxidative protein folding
    Okada, Shunsuke; Matsusaki, Motonori; Arai, Kenta; Hidaka, Yuji; Inaba, Kenji; Okumura, Masaki; Muraoka, Takahiro
    CHEMICAL COMMUNICATIONS
    ROYAL SOC CHEMISTRY
    Coupling of thiol and urea-type -NHC(=X)NH2 (X = O or NH) groups is effective in promoting oxidative protein folding. In particular, a thiol compound coupled with a guanidyl (X = NH) group significantly accelerates the rates of folding processes and enhances the yields of native proteins.
    2019年01月18日, 研究論文(学術雑誌), 共同, 55, 6, 1359-7345, DOI(公開)(r-map), 759, 762
  • Heat-Triggered Crystallization of Liquid Crystalline Macrocycles Allowing for Conductance Switching through Hysteretic Thermal Phase Transitions
    Takahiro Muraoka, Tatsuya Shima, Takashi Kajitani, Norihisa Hoshino, Estelle Morvan, Axelle Grélard, Erick J. Dufourc, Takanori Fukushima, Tomoyuki Akutagawa, Kota Nabeya, and Kazushi Kinbara
    Chemistry An Asian Journal
    Wiley
    2019年01月04日, 研究論文(学術雑誌), 共同, 14, 1, DOI(公開)(r-map), 141, 148
  • Design of C-2-symmetric alkaloidal chiral amphiphiles and configurational effects on self-assembly
    Tsuchiya, Nana; Ryu, Yunosuke; Muraoka, Takahiro; Oguri, Hiroki
    ORGANIC & BIOMOLECULAR CHEMISTRY
    ROYAL SOC CHEMISTRY
    Alkaloids are a cornerstone in the development of medicinal and synthetic compounds due to their capability of specific recognition of targeted biomacromolecules, and uses in optical resolution and asymmetric reactions. To explore the untapped potential of the rigid and densely functionalized structures of alkaloids with precisely regulated configurations as optically active core scaffolds of self-assembling molecules, here we report the design, syntheses, chiroptical properties and self-assemblies of C-2-symmetric alkaloidal amphiphiles with anti/syn stereochemical variations. Bispyrrolidinoindoline (BPI) was chosen as the optically active core scaffold. It was synthetically modified with hydrophobic alkyl chains and hydrophilic tetraethylene glycol tails to provide amphiphilicity. The anti/syn configurational differences in the amphiphiles significantly influenced the chiroptical, dynamic and supramolecular properties. Amphiphiles with anti-configurations responded to a solvent polarity change by altering their conformations, while the conformational changes of the syn-type amphiphiles were largely restricted. Furthermore, the anti-type amphiphile having the highest structural flexibility showed a characteristic split Cotton effect in an organic medium and formed the largest aggregates upon addition of water with a significant change in the circular dichroism (CD) profile, while amphiphiles having conformational restriction by the syn-configuration or a macrocyclic structure showed monomodal CD signals and afforded significantly smaller aggregates upon addition of water. Hence, the C-2-symmetric alkaloidal BPI structure is demonstrated to be a useful core scaffold for supramolecular chemistry to design amphiphiles with controllable configurational diversity, which allows for the customization of chiroptical properties, conformational flexibility and self-assembly.
    2018年12月28日, 研究論文(学術雑誌), 共同, 16, 48, 1477-0520, DOI(公開)(r-map), 9305, 9313
  • Localization of transmembrane multiblock amphiphilic molecules in phase-separated vesicles
    Kinbara, Kazushi; Umetsu, Kaori; Sonobe, Hiroki; Muraoka, Takahiro; Shimokawa, Naofumi; Takagi, Masahiro
    FARADAY DISCUSSIONS
    ROYAL SOC CHEMISTRY
    A series of triblock amphiphilic molecules bearing hydrophilic PEG chains at both ends of the long aromatic hydrophobic moieties were obtained serendipitously. The molecules involve linearly connected diarylethyne and diarylbutadiyne units, which show characteristic emissions upon excitation by UV light. These emissions showed red-shifts upon an increase in the solvent polarity, where the shifts are larger for the molecules with longer aromatic moieties. The distribution of these molecules in phase-separated membranes consisting of DOPC/DPPC/cholesterol was studied by fluorescence microscopy. It was found that most compounds, except for that with the longest hydrophobic unit, were selectively distributed in the Ld phase consisting mainly of DOPC. Interestingly, some of them were suggested to encourage delocalization of cholesterol in both the Lo and Ld phases.
    2018年09月01日, 研究論文(学術雑誌), 共同, 209, 1359-6640, DOI(公開)(r-map), 315, 328
  • Bio-inspired Multiblock Molecules for Membrane Functionalization
    Muraoka, Takahiro
    BIOLOGICAL & PHARMACEUTICAL BULLETIN
    PHARMACEUTICAL SOC JAPAN
    A multipass transmembrane (MTM) structure is prevalent in membrane proteins for a wide range of functions. Typically, the MTM structure is constructed of bundled multiple alpha-helices spanning the membrane which are connected by flexible domains. One characteristic feature of MTM proteins is dynamic functions such as stimuli responses and conformational changes. In this review, the development of synthetic molecules forming an MTM structure in membranes is highlighted. The MTM folded structure is developed using an amphiphilic molecular design with a multiblock strategy between rigid hydrophobic components and flexible hydrophilic units. Such synthetic amphiphiles not only form the MTM structure by folding but also self-assemble to construct supramolecular ion channels. An elaborated molecular design of the MTM structure with a ligand-binding pocket allows for ligand-gated regulation of ion transport. Light-triggered membrane deformation for vesicle budding is also demonstrated.
    2018年03月, 研究論文(学術雑誌), 単独, 41, 3, 0918-6158, DOI(公開)(r-map), 294, 302
  • Enzymatically cleavable traceless biotin tags for protein PEGylation and purification
    Wawro, Adam M.; Aoki, Yusuke; Muraoka, Takahiro; Tsumoto, Kouhei; Kinbara, Kazushi
    CHEMICAL COMMUNICATIONS
    ROYAL SOC CHEMISTRY
    Here we report an example of a protein-PEG conjugate with a biotin tag cleavable by lipase-catalyzed hydrolysis. Very mild cleavage conditions, heterogeneous, easily separable catalysts, and traceless design make this method attractive for the preparation and purification of PEGylated proteins.
    2018年02月21日, 研究論文(学術雑誌), 共同, 54, 15, 1359-7345, DOI(公開)(r-map), 1913, 1916
  • Multifarious Polymorphism of a Multiblock Amphiphilic Macrocycle Bearing Thermally Responsive Polyether Segment
    Muraoka, Takahiro; Shima, Tatsuya; Kinbara, Kazushi
    ACS OMEGA
    AMER CHEMICAL SOC
    Formation of multiple crystalline phases of a multiblock amphiphilic macrocycle AT2B is demonstrated. AT2B forms a single crystal (Cr-alpha) by vapor diffusion and shows reversible single-crystal-to-single-crystal transition between two crystalline phases (Cr-alpha and Cr-beta) by a temperature change, and crystalline AT2B (Cr-beta) melts at 422 K, and the cooling rate from the melt influences the phase of the solid formed. By cooling at 1.0 K min(-1), AT2B forms crystalline phases (Cr-gamma and Cr-delta), which are different from both Cr-alpha and Cr-beta. On the other hand, cooling at 2.0 K min(-1) results in the formation of an amorphous phase, and a mechanical stress also triggers a crystal-to-amorphous solid transition. Interestingly, the amorphous solid crystallizes to give the fifth crystalline phase (Cr-gamma) upon heating before melting. It is suggested that these multiple phase transitions are driven by thermal conformational changes at the tetraethylene glycol chains of AT2B.
    2018年01月, 研究論文(学術雑誌), 共同, 3, 1, 2470-1343, DOI(公開)(r-map), 414, 418
  • Mechano-Sensitive Synthetic Ion Channels
    Muraoka, Takahiro; Umetsu, Kaori; Tabata, Kazuhito V.; Hamada, Tsutomu; Noji, Hiroyuki; Yamashita, Takashi; Kinbara, Kazushi
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
    AMER CHEMICAL SOC
    Mechanical stress is a ubiquitous stimulus sensed by membrane proteins, but rarely by synthetic molecules. Inspired by mechano-sensitive ion channels found in cell membranes, tension-responsive transmembrane multiblock amphiphiles were developed. In membranes, a single-transmembrane amphiphile responds to both expanding and contracting tensions to weaken and strengthen the stacking of membrane-spanning units, respectively, and ion transportation is triggered by expanding tension to form a supramolecular channel, while little transportation is observed under a tensionless condition. In contrast, a three-transmembrane amphiphile showed little spectroscopic response to tensions, likely due to weaker stacking of membrane-spanning units than in the single-transmembrane amphiphile. Nevertheless, the three-transmembrane amphiphile shows ion transportation by forming a unimolecular channel even under a tensionless condition, and the ion-transporting activity decreased with expanding tension. Interestingly, the estimated operating force of these synthetic systems was comparable to that of the mechano-sensitive proteins. This study opens the door toward new mechano-sensitive molecular devices.
    2017年12月, 研究論文(学術雑誌), 共同, 139, 49, 0002-7863, DOI(公開)(r-map), 18016, 18023
  • Thermally-induced lateral assembly of a PEG-containing amphiphile triggering vesicle budding
    Li, Rui; Muraoka, Takahiro; Kinbara, Kazushi
    CHEMICAL COMMUNICATIONS
    ROYAL SOC CHEMISTRY
    A macrocyclic amphiphile consisting of a thermo-responsive octaethylene glycol chain with hydrophobic aromatic and aliphatic units undergoes lateral self-assembly in a liquid-disordered-state phospholipid bilayer membrane upon heating, which further leads to vesicle budding.
    2017年11月, 研究論文(学術雑誌), 共同, 53, 85, 1359-7345, DOI(公開)(r-map), 11662, 11665
  • Stimuli-responsive multi-block molecules
    Muraoka, Takahiro
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
    AMER CHEMICAL SOC
    2017年08月, 研究論文(学術雑誌), 単独, 254, 0065-7727
  • Newly characterized interaction stabilizes DNA structure: oligoethylene glycols stabilize G-quadruplexes CH-pi interactions
    Tateishi-Karimata, Hisae; Ohyama, Tatsuya; Muraoka, Takahiro; Podbevsek, Peter; Wawro, Adam M.; Tanaka, Shigenori; Nakano, Shu-ichi; Kinbara, Kazushi; Plavec, Janez; Sugimoto, Naoki
    NUCLEIC ACIDS RESEARCH
    OXFORD UNIV PRESS
    Oligoethylene glycols are used as crowding agents in experiments that aim to understand the effects of intracellular environments on DNAs. Moreover, DNAs with covalently attached oligoethylene glycols are used as cargo carriers for drug delivery systems. To investigate how oligoethylene glycols interact with DNAs, we incorporated deoxythymidine modified with oligoethylene glycols of different lengths, such as tetraethylene glycol (TEG), into DNAs that form antiparallel G-quadruplex or hairpin structures such that the modified residues were incorporated into loop regions. Thermodynamic analysis showed that because of enthalpic differences, the modified G-quadruplexes were stable and the hairpin structures were slightly unstable relative to unmodified DNA. The stability of G-quadruplexes increased with increasing length of the ethylene oxides and the number of deoxythymidines modified with ethylene glycols in the G-quadruplex. Nuclear magnetic resonance analyses and molecular dynamics calculations suggest that TEG interacts with bases in the G-quartet and loop via CH-pi and lone pair-pi interactions, although it was previously assumed that oligoethylene glycols do not directly interact with DNAs. The results suggest that numerous cellular co-solutes likely affect DNA function through these CH-pi and lone pair-pi interactions.
    2017年07月, 研究論文(学術雑誌), 共同, 45, 12, 0305-1048, DOI(公開)(r-map), 7021, 7030

著書

  • Supramolecular Chemistry of Multiblock Amphiphiles
    Takahiro Muraoka
    Wiley VCH
    2023年
  • Protein Aggregation Suppression and Folding Promotion by Synthetic Molecules
    Takahiro Muraoka
    Royal Society of Chemistry
    2021年06月11日
  • Molecular Technology for Membrane Functionalization in Molecular Technology, Volume 2: Life Innovation
    Michio Murakoshi, Takahiro Muraoka
    Wiley
    2018年12月10日

研究発表、招待講演等

  • 遅延制御によるタンパク質高次構造構築とバイオ展開
    第12回バイオ関連化学シンポジウム若手フォーラム
    2025年09月01日, 口頭発表(招待・特別)
  • 神経組織を再生する蛋白質の人工集積化
    第25回日本蛋白質科学会年会
    2025年06月18日, 口頭発表(招待・特別)
  • Protein-incorporating Self-assembling Peptides for Injured Brain Regeneration
    International Seminar on Bioengineering 2025
    2025年02月17日, 口頭発表(招待・特別)
  • Protein-incorporating self-assembling peptides for injured brain regeneration
    6th International Symposium on Pathomechanisms of Amyloid Diseases
    2024年12月04日, 口頭発表(招待・特別)
  • 遅延制御による高次構造構築とバイオ応用
    関東高分子若手研究会2024 秋の講演会
    2024年10月26日, 口頭発表(招待・特別)
  • 北里大学未来工学部シンポジウム
    2024年07月06日, 口頭発表(招待・特別)
  • 機能的相分離材料の人工構築
    第24会日本蛋白質科学会年会ー相分離遅延を可視化する先端技術ー
    2024年06月13日, 口頭発表(招待・特別)
  • Injured brain regeneration by protein-incorporating self-assembling peptides
    Pre-symposium of ISBC2024 in Nara
    2024年04月22日, 口頭発表(招待・特別)
  • レドックス制御によるタンパク質フォールディング促進
    日本薬学会第144年会「構造薬科学 -“分子”構造を見る、知る、操る-」
    2024年03月28日, 口頭発表(招待・特別)
  • 損傷脳機能回復を促す自己集合ペプチド分子技術
    日本薬学会第144年会「中分子創薬に資する次世代分子技術」
    2024年03月28日, 口頭発表(招待・特別)
  • 膜輸送分子技術の構築と応用
    ケムステVシンポ「ペプチドと膜が織りなす超分子生命工学」
    2023年11月21日, 口頭発表(招待・特別)
  • A Membrane-expanding Molecular Machine Triggering Endocytosis and Virus Encapsulation for in vivo Delivery
    第59回工学とバイオセミナー(東京大学生産技術研究所)
    2023年11月17日, 口頭発表(招待・特別)
  • 遅延制御が拓く生体模倣化学
    京都大学工学部
    2023年11月15日, 口頭発表(招待・特別)
  • 損傷脳を再生する自己集合性ペプチド材料
    第96回日本生化学会大会
    2023年10月31日, 口頭発表(招待・特別)
  • 可視光で駆動する巨大膜変形と能動輸送
    「細胞を創る」研究会16.0シンポジウム
    2023年09月25日, 口頭発表(招待・特別)
  • 速度論効果を利用する多段階蛋白質フォールディング促進
    日本化学会 第103春季大会(2023)
    2023年03月25日, 口頭発表(招待・特別)
  • 膜変形分子機械の開発と生体内輸送への応用
    令和4年度東北地区先端高分子セミナー
    2023年03月07日, 口頭発表(招待・特別)
  • Functional assembly of polypeptides for injured brain regeneration
    ZOOMinar series on “Molecular Basis of Proteinopathies”
    2023年02月06日, 口頭発表(招待・特別)
  • Development of a novel gel-forming peptide with helix-to- strand transition capability for injured brain regeneration
    The 16th Asian Textile Conference (ATC-16)
    2022年10月28日, ポスター発表
  • 膜融合を発現する分子機械を用いた光応答性ベシクルの開発と応用
    第12回CSJ化学フェスタ2022
    2022年10月18日, ポスター発表
  • 酸化的タンパク質フォールディングを促進するチオール化合物の開発と電荷効果
    第12回CSJ化学フェスタ2022
    2022年10月18日, ポスター発表
  • 自己集合性ペプチドの親水部変換によるバイオ機能制御
    第12回CSJ化学フェスタ2022
    2022年10月18日, ポスター発表
  • 多段階反応システムによるタンパク質フォールディング促進
    第16回バイオ関連化学シンポジウム
    2022年09月10日, 口頭発表(一般)
  • Endocytosis-like Vesicle Fission by Membrane Expanding Molecular Machine Enabling Efficient Encapsulation of Huge Biomacromolecules
    第71回高分子討論会
    2022年09月07日, 口頭発表(一般)
  • 天然物骨格を活用した8の字型キラル中分子群の設計・合成・キロプテイカル特性
    第64回天然有機化合物討論会
    2022年09月07日, 口頭発表(一般)
  • 組木型パッキングを構成する両親媒性ペプチドのゲル特性、精密構造解析と脳梗塞治療応用
    第71回高分子討論会
    2022年09月05日, ポスター発表
  • チオール化合物への電荷付与が酸化的タンパク質フォールディング促進に与える効果
    第71回高分子討論会
    2022年09月05日, ポスター発表
  • 酵素模倣型酸化的フォールディング促進剤による濃縮環境での多段階触媒システムの実証
    第71回高分子討論会
    2022年09月05日, ポスター発表
  • 液液相分離の制御に向けた水溶性ブロックポリマー
    第71回高分子討論会
    2022年09月05日, ポスター発表
  • Regulated folding and assembly of polypeptides for designing ECM-mimetic biomaterials
    Protein Folding, Aggregation, Misfolding Disease, and Disease Crosstalk
    2022年09月02日, 口頭発表(招待・特別)
  • Neurochemistry from Supramolecular Chemistry
    Neuro2022
    2022年07月02日, 口頭発表(招待・特別)
  • プラズマによって誘起されるタンパク質液-液相分離現象の解明
    第34回日本機械学会バイオエンジニアリング講演会
    2022年06月25日, ポスター発表
  • キネティクス操作に基づく酸化的蛋白質フォールディング制御
    蛋白質科学会「キネティクスから理解する生命システム」ワークショップ
    2022年06月08日, 口頭発表(招待・特別)
  • カチオン性基を有するチオール化合物のタンパク質フォールディング促進効果
    第71回高分子学会年次大会
    2022年05月26日, ポスター発表
  • 高次構造転移特性を有する自己集合性ペプチドの開発と組織再生への応用
    第71回高分子学会年次大会
    2022年05月25日, ポスター発表
  • 巨大生体高分子の高効率封入を可能にする光応答性エンドサイトーシスの実現とin vivoファージディスプレイ法への応用
    日本薬学会第142年会
    2022年03月26日, 口頭発表(一般)
  • リン脂質膜変形分子素子の開発(1):光応答性両親媒性分子を用いたエンドサイトーシス様ベシクル分裂
    日本化学会 第102春季大会(2022)
    2022年03月24日, 口頭発表(一般)
  • 生体酵素模倣を指向したタンパク質酸化的フォールディング促進剤の開発
    日本化学会 第102春季大会(2022)
    2022年03月24日, 口頭発表(一般)
  • 高次構造転移特性を有するヒドロゲル化ペプチドの開発と組織再生への応用
    日本化学会 第102春季大会(2022)
    2022年03月24日, 口頭発表(一般)
  • 酸化的タンパク質フォールディングを操作するポリカチオン化合物の開発
    日本化学会 第102春季大会(2022)
    2022年03月24日, 口頭発表(一般)
  • 芳香族化合物による酸化的タンパク質フォールディング促進効果
    日本化学会 第102春季大会(2022)
    2022年03月24日, 口頭発表(一般)
  • 凝集抑制効果を併せ持った酸化的タンパク質フォールディング促進剤の開発
    日本化学会 第102春季大会(2022)
    2022年03月24日, 口頭発表(一般)
  • 液液相分離を利用した酸化的タンパク質フォールディング操作
    日本化学会 第102春季大会(2022)
    2022年03月24日, 口頭発表(一般)
  • リン脂質膜変形分子素子の開発(2): チューブ状リン脂質膜の形成を誘導するCaRLペプチドの設計と応用
    日本化学会 第102春季大会(2022)
    2022年03月24日, 口頭発表(一般)
  • 凝集抑制効果を併せ持った酸化的タンパク質フォールディング促進剤の開発
    2022年03月24日, 口頭発表(一般)
  • 自己集合性ペプチドを用いた神経組織再生
    第3回タタバイオ分子クラブ
    2022年03月22日, 口頭発表(招待・特別)
  • 新規微生物ラベル化法による環境浄化に有効な微生物の単離技術
    公益財団法人鉄鋼環境基金2021年度 第4回研究討論会(土壌・水質分野)
    2022年03月14日, 口頭発表(招待・特別)
  • Development of synthetic amphiphilic peptides with bio-functions and stimuli-responses
    Pacifichem 2021
    2021年12月20日, ポスター発表
  • Redox-active Synthetic Molecules for Promotion of Oxidative Protein Folding
    Pacifichem 2021
    2021年12月19日, ポスター発表
  • Effects of redox-active compounds with aromatic units for promotion of oxidative protein folding
    Pacifichem 2021
    2021年12月19日, ポスター発表
  • Membrane Deformation Induced by Self-assembly of Synthetic Lipids on Phospholipid Bilayer
    Pacifichem 2021
    2021年12月18日, ポスター発表
  • Glycine Substitution Effects on Supramolecular Morphology and Thermal Response of Self-Assembling Peptides
    Pacifichem 2021
    2021年12月16日, 口頭発表(招待・特別)
  • 粘弾性を調節した超分子ペプチドゲルの開発と脳梗塞の再生治療
    第44回 日本分子生物学会
    2021年12月03日, 口頭発表(一般)
  • 合成化学アプローチによるジスルフィド結合異性化酵素の模倣
    第44回 日本分子生物学会年会
    2021年12月01日, 口頭発表(招待・特別)
  • VEGFを徐放する超分子ペプチドの開発と亜急性期脳梗塞の再生治療
    第43回日本バイオマテリアル学会大会
    2021年11月28日, 口頭発表(一般)
  • 高次構造転移し超分子ゲルを形成する新規自己集合性ペプチドの開発と応用
    第11回CSJ化学フェスタ2021
    2021年10月20日, ポスター発表
  • リン脂質膜上での分子集合によって誘導されるチューブ膜変形現象
    第11回CSJ化学フェスタ2021
    2021年10月20日, ポスター発表
  • 二次構造転移を伴う自己集合性ペプチドの開発とゲル形成特性
    日本化学会秋季事業 第11回 CSJ化学フェスタ2021
    2021年10月19日, ポスター発表
  • 光膜変形を駆動する両親媒性分子の開発
    日本化学会秋季事業 第11回 CSJ化学フェスタ2021
    2021年10月19日, ポスター発表
  • 光応答膜変形を利用したベシクルの融合
    日本化学会秋季事業 第11回 CSJ化学フェスタ2021
    2021年10月19日, ポスター発表
  • タンパク質酸化的フォールディングを促進するチオール化合物の分子骨格効果
    日本化学会秋季事業 第11回 CSJ化学フェスタ2021
    2021年10月19日, ポスター発表
  • 生きた細胞膜で機能する人工イオンチャネル
    第6回ABC-InFO
    2021年09月22日, 口頭発表(招待・特別)
  • リン脂質膜上での分子集合によって誘導される膜変形現象
    第15回バイオ関連化学シンポジウム
    2021年09月09日, 口頭発表(一般)
  • 分子中央部へのアルキレン鎖導入によるペプチド集積化と生物学的機能化
    第15回バイオ関連化学シンポジウム
    2021年09月09日, ポスター発表
  • タンパク質酸化的フォールディングを促進する低分子化合物の官能基配置効果
    第15回バイオ関連化学シンポジウム
    2021年09月08日, ポスター発表
  • アルキレン鎖導入ペプチドの超分子ファイバー形態と機能
    日本化学会 生体機能関連化学部会 若手の会 第32回サマースクール
    2021年07月16日, ポスター発表
  • 人工イオンチャネルの全原子分子動力学シミュレーション
    第21回日本蛋白質科学会年会
    2021年06月16日, 口頭発表(一般)
  • Self-assembly of Amphiphilic Peptide in Phospholipid Membrane
    第38回国際フォトポリマーコンファレンス(ICPST-38 (2021) )
    2021年06月15日, 口頭発表(招待・特別)
  • アルキレン鎖を導入した両親媒性ペプチドの自己集合特性と生物学的機能
    第1回発動分子科学研究会
    2021年06月11日, ポスター発表
  • 光応答性分子機械を用いたエンドサイトーシス様のベシクル分裂
    発動分子科学研究会
    2021年06月11日, ポスター発表
  • リン脂質膜上での分子集合によって誘導される膜変形現象
    発動分子科学研究会
    2021年06月11日, ポスター発表
  • 自己集合性ペプチド中央へのアルキレン鎖導入効果
    2021年繊維学会年次大会
    2021年06月09日, ポスター発表
  • 人工膜変形素子の開発:リン脂質膜上での分子接着によって誘導される膜変形現象
    第70回高分子学会年次大会
    2021年05月28日, 口頭発表(一般)
  • 人工膜変形素子の開発:光応答性分子機械を用いたエンドサイトーシスのようなベシクル分裂
    第70回高分子学会年次大会
    2021年05月28日, 口頭発表(一般)
  • グラム陽性菌に対する生体分子導入に向けた膜透過性ペプチドの検討
    第21回マリンバイオテクノロジー学会
    2021年05月15日, ポスター発表
  • タンパク質酸化的フォールディングを促進する低分子化合物の分子骨格効果
    日本化学会春季年会
    2021年03月22日, 口頭発表(一般)
  • 二次構造変化を示す自己集合性ペプチドの開発と高強度ゲルの構築
    日本化学会春季年会
    2021年03月22日, 口頭発表(一般)
  • タンパク質酸化的フォールディングを促進する低分子化合物の置換基効果
    日本化学会春季年会
    2021年03月22日, 口頭発表(一般)
  • リポソーム内部でのリン脂質合成による自己複製機構の構築
    細胞を創る研究会
    2020年11月12日, ポスター発表
  • 膜タンパク質から着想した両親媒性ペプチドのゲル化挙動
    繊維学会秋季研究発表会
    2020年11月06日, 口頭発表(一般)
  • 生体内環境で機能する超分子
    高分子学会第63回茨城地区活動講演会
    2020年11月05日, 口頭発表(招待・特別)
  • 人工膜小胞内リン脂質合成による自律的細胞分裂機構の構築
    CSJ化学フェスタ
    2020年10月20日, ポスター発表
  • 高い強度と刺激応答性を兼ね備えた超分子ペプ チドゲル化剤の開発と応用
    CSJ化学フェスタ
    2020年10月20日, ポスター発表
  • Protein Stabilization by Small Organic Molecules
    令和2年度化学系学協会東北大会 有機化学コロキウム
    2020年09月26日, 口頭発表(招待・特別)
  • Development of a self-reproducing vesicular system driven by internal phospholipid synthesis
    第58回日本生物物理学会年会
    2020年09月17日, ポスター発表
  • タンパク質酸化的フォールディングを促進するチオール化合物の新たな分子デザイン
    日本化学会 第100春季年会 (2020)
    2020年03月22日, 口頭発表(一般)
  • Morphological Changes of Self-assembled Structures by Single-Bond Rotating Motion
    pi-EJ 2019
    2019年11月13日, ポスター発表
  • Development of Membrane Penetrating Substances for Bacteria
    pi-EJ 2019
    2019年11月13日, ポスター発表
  • Macroscopic Membrane Deformation by Stimuli-responsive Functional Molecules
    pi-EJ 2019
    2019年11月13日, ポスター発表
  • Structured PEGs for Protein Stabilization
    International Symposium on Disordered Proteins, Protein Folding, and Disease-causing Aggregation
    2019年10月25日, 口頭発表(招待・特別)
  • All-atom molecular dynamics simulations of artificial ion channels
    情報計算化学生物学会(CBI学会2019年大会)
    2019年10月22日, ポスター発表
  • Development of Membrane Penetrating Substances for Microbes
    CSJ化学フェスタ
    2019年10月16日, ポスター発表
  • Redoxで発動するタンパク質フォールディング
    高分子討論会
    2019年09月26日, 口頭発表(招待・特別)
  • 人工イオンチャネルの分子動力学シミュレーション
    生物物理学会
    2019年09月24日, 口頭発表(一般)
  • 分子の動きから発想するバイオ材料化学
    東京大学工学部応用化学科野地研究室セミナー
    2019年09月18日, 口頭発表(招待・特別)
  • 新規レドックス分子のデザイン法確立と酸化的フォールディングへの応用
    第92回日本生化学会大会
    2019年09月18日, 口頭発表(一般)
  • 微生物膜透過性を有するペプチドの探索と評価
    日本微生物生態学会
    2019年09月12日, 口頭発表(一般)
  • Cell-penetrating-peptides potentially enhances biomolecule delivery in bacteria
    Marine Biotechnology Conference 2019
    2019年09月09日, 口頭発表(一般)
  • Identification of factors hindering cell-penetrating peptide permeabilization
    Marine Biotechnology Conference 2019
    2019年09月09日, 口頭発表(一般)
  • Synthetic Promotors of Oxidative Protein Folding
    10th RSC-CSJ Joint Symposium – Chemistry for Complex Biological Systems –
    2019年09月07日, ポスター発表
  • Development of Membrane Penetrating Substances for Microbes
    バイオ関連化学シンポジウム
    2019年09月05日, ポスター発表
  • Morphological Changes of Self-assembled Structures by Single-bond Rotating Motion
    バイオ関連化学シンポジウム
    2019年09月04日, ポスター発表
  • Development of Redox Molecules Accelerating Oxidative Protein Folding
    バイオ関連化学シンポジウム
    2019年09月04日, ポスター発表
  • ペプチド集合体の形態と動的特性に与えるグリシン置換の効果
    バイオ関連化学シンポジウム
    2019年09月04日, ポスター発表
  • ウレア基を付与したチオールによる酸化的タンパク質フォールディングの促進
    バイオ関連化学シンポジウム
    2019年09月04日, 口頭発表(一般)
  • タンパク質を安定化する低分子の新設計
    有機合成化学協会 関東支部ミニシンポジウムー湘南2019ー
    2019年07月06日, 口頭発表(招待・特別)
  • Protein Folding Acceleration by Redox-Active Molecules
    東京大学工学系研究科化学生命工学専攻講演会「化学と生命のかけはし」
    2019年07月05日, 口頭発表(招待・特別)
  • Protein Folding Acceleration by Redox-Active Molecules
    10th International Conference on Molecular Electronics and Bioelectronics (M&BE10)
    2019年06月27日, 口頭発表(一般)
  • 新規レドックス分子による酸化的フォールディングの促進と応用
    第19回日本蛋白質科学会年会 第71回日本細胞生物学会大会
    2019年06月24日, 口頭発表(一般)
  • 精密分子構造修飾に基づくペプチド集合体の物性制御
    繊維学会
    2019年06月07日, 口頭発表(一般)
  • Cell-penetrating-peptides as carriers for biomolecule transfer into bacteria
    日本細菌学会
    2019年04月23日, 口頭発表(一般)
  • ウレア骨格を有するチオール化合物の酸化的タンパク質フォールディング促進効果
    第99回日本化学会春季年会
    2019年03月19日, 口頭発表(一般)
  • Design and Synthesis of C2-Symmetric Alkaloidal Chiral Amphiphiles and Configurational Effects on Self-Assembly
    第99回日本化学会春季年会
    2019年03月18日, 口頭発表(一般)
  • Protein Cyborgization by Main Chain Substitution
    第99回日本化学会春季年会
    2019年03月18日, 口頭発表(一般)
  • 大腸菌の膜透過性を有するペプチドの探索と評価
    第99回日本化学会春季年会
    2019年03月17日, ポスター発表
  • 新規刺激応答性自己組織化ペプチドの設計
    第99回日本化学会春季年会
    2019年03月17日, ポスター発表
  • 単結合ねじれ運動を利用した分子集合体形状変換
    第99回日本化学会春季年会
    2019年03月17日, ポスター発表
  • Development of multiblock arene-perfluoroarene macrocycle
    第99回日本化学会春季年会
    2019年03月17日, 口頭発表(一般)
  • グアニジル基を用いた蛋白質酸化的フォールディング促進剤の開発
    第18回東北大学多元物質科学研究所 研究発表会
    2018年12月13日, ポスター発表
  • Thiol-containing Compounds for Acceleration of Protein Folding
    10th International Peptide Symposium
    2018年12月07日, ポスター発表
  • Development of Reducing Agents Accelerating Protein Folding
    π-EJ 2018, European–Japanese Workshop 2018
    2018年11月06日, ポスター発表
  • Stimuli–Responsive Multiblock Molecules in Membrane and Crystal
    π-EJ 2018, European–Japanese Workshop 2018
    2018年11月06日, 口頭発表(招待・特別)
  • タンパク質酸化的リフォールディングを促進する還元剤の新たな分子デザイン
    CSJ化学フェスタ2018
    2018年10月23日, ポスター発表
  • 水中での動的分子集合体の開発
    第5回π造形科学若手研究会
    2018年10月05日, ポスター発表
  • 刺激応答性分子の開発とその固体物性
    第5回π造形科学若手研究会
    2018年10月05日, ポスター発表
  • 機能性ペプチドの開発と評価
    第5回π造形科学若手研究会
    2018年10月05日, ポスター発表
  • 生体分子を模倣し操作する超分子化学
    π造形コロキウム(防衛大学校)
    2018年09月19日, 口頭発表(招待・特別)
  • タンパク質酸化的リフォールディング促進剤の開発
    第12回バイオ関連化学シンポジウム
    2018年09月09日, ポスター発表
  • 地球環境を支える希少微生物を 生きたまま解析し保存する基盤技術の開発
    平成 30 年度公益信託『エスペック地球環境研究・技術基金』授与式
    2018年08月24日, 口頭発表(招待・特別)
  • 有機合成化学を基盤とするタンパク質・細胞操作
    NCNP-TUAT若手研究シンポジウム2018夏
    2018年08月07日, 口頭発表(招待・特別)
  • 生体親和性分子を用いた酵素安定化技術の開発
    第19回酵素応用シンポジウム
    2018年06月01日, 口頭発表(招待・特別)
  • 光応答性両親媒性ペプチドを用いた細胞接着制御
    第17回日本再生医療学会総会
    2018年03月21日, 口頭発表(招待・特別)
  • 膜タンパク質模倣からデザインする人工イオンチャネルの開発
    応用物理学会分子バイオエレクトロニクス分科会
    2018年03月06日, 口頭発表(招待・特別)
  • タンパク質模倣から着想する機能性分子開発
    多元研若手研究者交流講演会
    2018年02月23日, 口頭発表(招待・特別)
  • 刺激応答性膜機能化分子の開発
    第4回π造形科学若手研究会
    2017年12月16日, ポスター発表
  • タンパク質安定化剤の開発
    第4回π造形科学若手研究会
    2017年12月16日, ポスター発表
  • 光応答自己集合性ペプチドの開発
    第4回π造形科学若手研究会
    2017年12月16日, ポスター発表
  • タンパク質から発想する機能性分子開発
    第4回π造形科学若手研究会
    2017年12月16日, 口頭発表(招待・特別)
  • Multiblock Molecules for Membrane Functionalization
    Symposium on Frontier of Biofunctional Chemistry, ISBC 2017 Pre-Symposium Meeting
    2017年12月12日, 口頭発表(招待・特別)
  • Bio-Inspired Multi-Block Amphiphiles
    Seminar at University of Bordeaux, LCPO
    2017年11月16日, 口頭発表(招待・特別)
  • Stimuli Responses of Multiblock Molecules with Aromatic and PEG Units
    π-System Figuration, German-Japanese Workshop
    2017年11月13日, 口頭発表(招待・特別)
  • 化学と生物の接点で展開する機能性分子の開発
    The 2nd FRIS Retreat / 若手研究者学際融合領域会
    2017年08月31日, 口頭発表(招待・特別)
  • タンパク質から学ぶマルチブロック型分子の開発と機能展開
    関東高分子若手研究会サマーキャンプ
    2017年08月02日, 口頭発表(招待・特別)
  • Bio-Inspired Multi-Block Amphiphiles
    Celebrating Four Decades of Research on Self-Assembling Materials
    2017年06月25日, 口頭発表(招待・特別)
  • Development of Multi-block Amphiphiles for Bio-related Functions
    International Symposium on Pure & Applied Chemistry (ISPAC) 2017
    2017年06月09日, 口頭発表(基調)
  • タンパク質操作に向けた有機化学的アプローチ
    最先端光計測とライフサイエンスの未来 ーBio. Phys. Chem.三重点の探索ー
    2017年03月04日, 口頭発表(招待・特別)
  • 生体から着想した硬さと柔らかさの組合せによる機能性分子の開発
    新学術領域研究「柔らかな分子系」ワークショップ「構造変化で操る分子の機能」
    2017年01月21日, 口頭発表(招待・特別)

外部研究資金等

  • タンパク質疾患治療技術を指向したタンパク質機能を肩代わりする合成分子の開発
    受託研究, 自 2017年02月01日, 至 2017年03月31日

委員歴

  • 公益財団法人 高分子学会
    行事委員 副委員長
    自 20240601, 至 20260531
  • 公益社団法人高分子学会
    編集委員
    自 20210401, 至 20230630

メディア報道

  • 東京農工大・徳島大・東北大、蛋白質の正しいフォールディングを助ける化合物を開発
    農工大らの研究チームが、高濃度の溶液内でタンパク質のフォールディングを正しく進める化合物を開発した、と掲載される。
    日経バイオテク
    自 2024年08月01日, 至 2024年08月01日
  • 東京農工大、100Mの高濃度条件でタンパク質フォールディングを促進する低分子化合物の開発に成功ー「寛容的」な基質認識が可能にする、タンパク質製剤の合成効率向上と認知症などの変性疾患治療への技術基盤ー
    農工大 村岡貴博教授ら研究グループは、ジスルフィド(SS)結合の形成を伴う酸化的タンパク質フォールディングを、初めて、サブmM(100μM)の高濃度条件で効率的に進める人工分子βCDWSHの開発に成功した、と掲載される。
    日経バイオテク
    自 2024年07月29日, 至 2024年07月29日
  • Tokyo University of Agriculture and Technology develop self-assembling peptides that protect cells and tissues from damage and oxidate stress
    The research groups of Tokyo University of Agriculture and Technology etc. has annouced that they successfully developed a self-assembling peptide (JigSAP-MMM)that is responsive to oxidative stress and protects cells and tissuesfrom oxidative damage.
    Science Japan
    自 2024年07月11日, 至 2024年07月11日
  • 酸化損傷から細胞保護東京農工大、ペプチド開発
    農工大の内田紀之特任講師と村岡貴博教授らは、参加による損傷から細胞や組織を保護する自己集合性ペプチドを開発した、と紹介される。
    日刊工業新聞
    自 2024年05月17日, 至 2024年05月17日
  • 最小量でタンパク質の立体構造形成を促進する化合物を開発、東京農工大らの研究グループ
    Pharm Tech Japan
    自 2023年07月06日, 至 2023年07月06日
  • 脳傷害後の神経再生を促す超分子バイオマテリアルの開発に成功
    名古屋市立大学大学院医学研究科脳神経科学研究所の澤本和延教授、大野雄也、中嶋智佳子、および同志社大学脳科学研究科の金子奈穂子教授らの研究グループは、東京医科歯科大学、東京農工大学、バレンシア大学の研究者と共同で、傷害を受けたマウスの脳を再生させるバイオマテリアルを開発したと紹介される。
    時事メディカル/マイナビニュース
    自 2023年02月02日, 至 2023年02月03日
  • VEGFを脳内で徐放するゲル
    東京農工大学の村岡貴博教授らの研究グループが、体内投与した箇所でタンパク質を効果的に徐放するゲル、ジグソー型ペプチド「JigSAP」を開発したことが紹介される。
    医療経済WEB
    自 2022年01月15日, 至 2022年01月15日
  • Jigsaw-shaped peptide solves tissue regeneration puzzle
    東京農工大学の村岡貴博教授らの研究グループが、体内投与した箇所でタンパク質を効果的に徐放するゲル、ジグソー型ペプチド「JigSAP」を開発したことが紹介される。
    Medical Express
    自 2022年01月13日, 至 2022年01月13日
  • 亜急性期脳梗塞 細胞フリー再生治療に道東京医科歯科大など
    東京農工大学の村岡貴博教授らの研究グループが、体内投与した箇所でタンパク質を除法する超分子ペプチドゲルを構築するペプチド「JigSAP(ジグサップ)」を開発したと発表したことが紹介される。
    科学新聞
    自 2021年12月03日, 至 2021年12月03日
  • 血管再生を促進するVEGFタンパク質徐放のゲル「JigSAP」を開発-東京医歯大ほか
    東京農工大学の村岡貴博教授らの研究グループが、体内投与した箇所でタンパク質を効果的に徐放するゲル、ジグソー型ペプチド「JigSAP」を開発したことが紹介される。
    Q Life Pro
    自 2021年11月24日, 至 2021年11月24日
  • 薄膜技術研究5人に助成金サムコ振興財団
    東京農工大学の村岡貴博教授がサムコ科学技術振興財団の研究助成対象者に選ばれたことが紹介される。
    京都新聞
    自 2021年07月13日, 至 2021年07月13日
  • 人工イオンチャネルを開発
    東京工業大学の金原数教授、東京農工大学の村岡貴博准教授らの研究グループが、神経伝達物質に応答してイオンを輸送する人工イオンチャネルを開発したことが紹介される。
    化学工業日報
    自 2020年07月01日, 至 2020年07月01日
  • ヒドロゲルの新たな力学強度・温度応答性制御法
    Chem-Station
    自 2019年11月11日, 至 2019年11月11日
  • 高い効率性や省エネルギー性を持つ人工たんぱく質の創出に期待
    お茶の水女子大学の三宅亮介講師と東京農工大学の村岡貴博准教授らの研究グループが、人工的にデザインしたペプチドを用いて、柔らかい小さな分子から、タンパク質に匹敵する巨大空間を作ることに成功したことが紹介される。
    大学ジャーナル
    自 2019年06月06日, 至 2019年06月06日
  • タンパク質合成へ基礎技術
    お茶の水女子大学の三宅亮介講師や東京農工大学の村岡貴博准教授らが、人工的にたんぱく質を作る基礎技術を開発したことが紹介される。
    日経産業新聞
    自 2019年05月31日, 至 2019年05月31日
  • 研究ハイライト タンパク質を正しく仕上げる
    現代化学
    自 2019年02月01日, 至 2019年02月28日
  • タンパク質の構造形成助ける薬剤開発に成功農工大・東北大の研究グループ
    東京農工大学大学院工学研究院応用化学部門の村岡貴博准教授らの研究グループが、タンパク質が正しく機能するために必要不可欠な酸化的フォールディングというステップを、細胞内で使用されているグタチオンよりも高い効率で促進する低分子“グアニジンチオール”を開発することに成功したことが紹介される。
    科学新聞
    自 2019年01月01日, 至 2019年01月01日

所属学協会

  • 日本微生物生態学会
  • 日本蛋白質科学会
  • 繊維学会
  • アメリカ化学会
  • 高分子学会
  • 日本化学会

受賞

  • マツダ財団
    マツダ研究助成奨励賞
    選択的分子捕捉材料の開発と応用
    2019年09月01日
  • エスペック
    公益信託 第21回エスペック地球環境研究奨励賞
    2018年10月16日
  • 東京農工大学
    学長賞
    2018年10月15日
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