研究者紹介システム

砂山 博文
スナヤマ ヒロブミ
大学院工学研究科 応用化学専攻
准教授
応用化学関係
Last Updated :2022/06/13

研究者情報

所属

  • 【主配置】

    大学院工学研究科 応用化学専攻

学位

  • 博士(工学), 神戸大学

研究ニュース

研究活動

研究分野

  • ライフサイエンス / 薬系分析、物理化学
  • ナノテク・材料 / ナノバイオサイエンス
  • ナノテク・材料 / 分析化学

受賞

  • 2020年11月 クロマトグラフィー科学会, 奨励賞

  • 2018年06月 10th International conference on molecular imprinting (MIP2018) Best Poster Award

  • 2018年05月 第78回分析化学討論会 産業界シンポジウム若手ポスター賞

  • 2022年04月 日本化学会第102春季年会 優秀講演賞 (産業)

  • 2021年11月 第32回クロマトグラフィー科学会議 Best Presentation Award

  • 2022年05月 第69回応用物理学会春季講演会 Poster Award

論文

  • Hirobumi SUNAYAMA, Toshifumi TAKEUCHI

    The Society for Chromatographic Sciences, 2021年05月31日, CHROMATOGRAPHY, 42 (2), 73 - 81

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    研究論文(学術雑誌)

  • Hirobumi Sunayama, Toshifumi Takeuchi

    Springer Science and Business Media LLC, 2021年05月17日, Analytical and Bioanalytical Chemistry, 413, 6183 - 6189

    [査読有り]

    研究論文(学術雑誌)

  • Takashi IKEGAMI, Ryoichi KATAOKA, Hirobumi SUNAYAMA, Toshifumi TAKEUCHI

    Japan Society for Analytical Chemistry, 2021年03月05日, 分析化学, 70 (3), 111 - 124

    [査読有り]

    研究論文(学術雑誌)

  • Hirobumi Sunayama, Kazuhiro Takamiya, Eri Takano, Ryo Horikawa, Yukiya Kitayama, Toshifumi Takeuchi

    The Chemical Society of Japan, 2021年02月15日, Bulletin of the Chemical Society of Japan, 94 (2), 525 - 531

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    研究論文(学術雑誌)

  • Katsuki Tsutsumi, Hirobumi Sunayama, Yukiya Kitayama, Eri Takano, Yuji Nakamachi, Ryohei Sasaki, Toshifumi Takeuchi

    Wiley, 2021年02月08日, Advanced NanoBiomed Research, 1 (4), 2000079 - 2000079

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    研究論文(学術雑誌)

  • Chehasan Cheubong, Eri Takano, Yukiya Kitayama, Hirobumi Sunayama, Kazuaki Minamoto, Ryota Takeuchi, Shunsuke Furutani, Toshifumi Takeuchi

    Pork contamination is a serious concern for the global halal food market because many manufacturers commonly use pork instead of beef to reduce production costs. In this study, a highly sensitive fluorescent molecularly imprinted polymer nanogel (F-MIP-NG)-based sensor was developed for rapid porcine serum albumin (PSA) detection to investigate pork contamination in halal meat extracts. F-MIP-NGs were prepared via molecular imprinting and conjugation with ATTO 647N as the fluorescent reporter molecule for the post-imprinting modification (PIM) and then immobilized on gold-coated sensor chips. For achieving rapid and easy measurement, the fluorescence response was measured using a custom-made liquid handling robot equipped with a fluorescence microscope. The fluorescence response increased with increasing PSA concentration. Under optimal conditions, the F-MIP-NG-based sensors exhibited high sensitivity, a detection limit of 40 pM, a linear range of 0.25-5 nM, and excellent affinity and selectivity towards PSA, compared to potentially interfering proteins. Moreover, it was more efficient to detect beef contamination in 1 wt% pork contamination compared to the real-time polymerase chain reaction. Collectively the good analytical performance, high rates of recovery in real meat extract samples, fast detection, and a low detection limit of pork contamination (0.1 wt%) indicated the potential of the proposed sensor for detecting PSA as a marker of pork contamination in halal meat samples. The proposed sensing system based on the MIPs would open a way to establish highly sensitive and rapid sensing systems (<5 min/sample) for food analysis.

    Elsevier BV, 2021年01月, Biosensors and Bioelectronics, 172, 112775 - 112775, 英語

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    研究論文(学術雑誌)

  • Takahiro Morishita, Aoi Yoshida, Natsuki Hayakawa, Kentaro Kiguchi, Chehasan Cheubong, Hirobumi Sunayama, Yukiya Kitayama, Toshifumi Takeuchi

    American Chemical Society (ACS), 2020年09月15日, Langmuir, 36 (36), 10674 - 10682

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    研究論文(学術雑誌)

  • Chehasan Cheubong, Aoi Yoshida, Yuki Mizukawa, Natsuki Hayakawa, Minako Takai, Takahiro Morishita, Yukiya Kitayama, Hirobumi Sunayama, Toshifumi Takeuchi

    Accurate, simple, and valuable analytical methods for detection of food contamination are rapidly expanding to evaluate the validity of food product quality because of ethnic considerations and food safety. Herein molecularly imprinted nanogels (MIP-NGs), capable of porcine serum albumin (PSA) recognition, were prepared as artificial molecular recognition elements. The MIP-NGs were immobilized on a quartz crystal microbalance (QCM) sensor for detection of pork contamination in real beef extract samples. The MIP-NGs-based QCM sensor showed high affinity and excellent selectivity toward PSA compared to reference serum albumins from five different animals. The high PSA specificity of MIP-NGs led to the detection of pork contamination with a detection limit of 1% (v/v) in real beef extract samples. We believe the artificial molecular recognition materials prepared by molecular imprinting are a promising candidate for halal food control.

    AMER CHEMICAL SOC, 2020年05月, ANALYTICAL CHEMISTRY, 92 (9), 6401 - 6407, 英語

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    研究論文(学術雑誌)

  • Toshifumi Takeuchi, Kisho Mori, Hirobumi Sunayama, Eri Takano, Yukiya Kitayama, Taku Shimizu, Yuzuki Hirose, Sachiko Inubushi, Ryohei Sasaki, Hirokazu Tanino

    Small extracellular vesicles (sEVs) are reliable biomarkers for early cancer detection; however, conventional detection methods such as immune-based assays and microRNA analyses are not very sensitive and require sample pretreatments and long analysis time. Here, we developed a molecular imprinting-based dynamic molding approach to fabricate antibody-conjugated signaling nanocavities capable of size recognition. This enabled the establishment of an easy-to-use, rapid, sensitive, pretreatment-free, and noninvasive sEV detection platform for efficient sEV detection-based cancer diagnosis. An apparent dissociation constant was estimated to be 2.4 x 10(-16) M, which was similar to 1000 times higher than that of commercial immunoassays (analysis time, 5 min/sample). We successfully used tears for the first time to detect cancer-related intact sEVs, clearly differentiating between healthy donors and breast cancer patients, as well as between samples collected before and after total mastectomy. Our nanoprocessing strategy can be easily repurposed for the specific detection of other types of cancer by changing the conjugated antibodies, thereby facilitating the establishment of liquid biopsy for early cancer diagnosis.

    American Chemical Society (ACS), 2020年04月08日, Journal of the American Chemical Society, 142 (14), 6617 - 6624, 英語

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    研究論文(学術雑誌)

  • Tetsuro Saeki, Eri Takano, Hirobumi Sunayama, Yuri Kamon, Ryo Horikawa, Yukiya Kitayama, Toshifumi Takeuchi

    Novel sequential post-imprinting modifications were demonstrated on the development of multi-functionalized molecularly imprinted polymers for a biomarker glycoprotein.

    Royal Society of Chemistry (RSC), 2020年, Journal of Materials Chemistry B, 8 (35), 7987 - 7993

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    研究論文(学術雑誌)

  • Tetsuro Saeki, Hirobumi Sunayama, Yukiya Kitayama, Toshifumi Takeuchi

    American Chemical Society (ACS), 2019年02月05日, Langmuir, 35 (5), 1320 - 1326

    [査読有り]

    研究論文(学術雑誌)

  • Eri Takano, Nobuaki Shimura, Yoshihisa Ujima, Hirobumi Sunayama, Yukiya Kitayama, Toshifumi Takeuchi

    American Chemical Society (ACS), 2019年01月31日, ACS Omega, 4 (1), 1487 - 1493

    [査読有り]

    研究論文(学術雑誌)

  • Morishige, T., Takano, E., Sunayama, H., Kitayama, Y., Takeuchi, T.

    2019年, ChemNanoMat, 5 (2), 224 - 229

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    研究論文(学術雑誌)

  • Kisho Mori, Mitsuhiro Hirase, Takahiro Morishige, Eri Takano, Hirobumi Sunayama, Yukiya Kitayama, Sachiko Inubushi, Ryohei Sasaki, Masakazu Yashiro, Toshifumi Takeuchi

    © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Exosomes are small (30–100 nm) membrane vesicles that serve as regulatory agents for intercellular communication in cancers. Currently, exosomes are detected by immuno-based assays with appropriate pretreatments like ultracentrifugation and are time consuming (>12 h). We present a novel pretreatment-free fluorescence-based sensing platform for intact exosomes, wherein exchangeable antibodies and fluorescent reporter molecules were aligned inside exosome-binding cavities. Such antibody-containing fluorescent reporter-grafted nanocavities were prepared on a substrate by well-designed molecular imprinting and post-imprinting modifications to introduce antibodies and fluorescent reporter molecules only inside the binding nanocavities, enabling sufficiently high sensitivity to detect intact exosomes without pretreatment. The effectiveness of the system was demonstrated by using it to discriminate between normal exosomes and those originating from prostate cancer and analyze exosomes in tear drops.

    2019年02月04日, Angewandte Chemie - International Edition, 58 (6), 1612 - 1615

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    研究論文(学術雑誌)

  • Yuichiro Sato, Kiminori Matsubara, Takanori Kubo, Hirobumi Sunayama, Yuta Hatori, Kinjiro Morimoto, Toshio Seyama

    Pseudomonas fluorescens lectin (PFL), which belongs to the high mannose (HM)-binding OAAH (Oscillatoria agardhii agglutinin homologue) lectin family, induces cancer cell death. However, the detailed mechanisms underlying this process have not yet been elucidated. We found that PFL decreased various integrins as well as EGFR in cancer cells by promoting internalization and autophagic degradation of these molecules, subsequently inducing caspase-8 dependent cell apoptosis. As revealed by an ex vivo angiogenesis assay using the rat aortic model, PFL inhibited neovascularization in a dose-dependent manner, which was potentially mediated by down-regulation of endothelium integrins. Interestingly, PFL also down-regulated B7-H4 in cancer cells, which has been implicated as a negative regulator of T cell-mediated immunity. We found that B7-H4 co-localized with β3 integrin in MKN28 gastric cancer cells. siRNA silencing of B7-H4 in MKN28 cells decreased expression of β3 integrin, suggesting physical and functional association between these molecules. Direct interaction of PFL with integrin αvβ3 or B7-H4 was examined by surface plasmon resonance analysis, which detected high affinity glycan-dependent binding to PFL. These investigations suggest that PFL interaction with cell surface integrins is a key process for the anti-cancer activities of PFL.

    2019年04月30日, Cancers, 11 (5), 英語, 国際誌

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    研究論文(学術雑誌)

  • Hiroki Matsumoto, Hirobumi Sunayama, Yukiya Kitayama, Eri Takano, Toshifumi Takeuchi

    Informa UK Limited, 2019年12月31日, Science and Technology of Advanced Materials, 20 (1), 305 - 312

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    研究論文(学術雑誌)

  • Toshifumi Takeuchi, Hirobumi Sunayama

    The molecular imprinting technology yields artificial materials capable of antibody-like molecular recognition. Molecularly imprinted materials are attractive because procedures for their preparation and use are comparatively simple. The number of research reports concerning molecularly imprinted polymers (MIPs) have been increasing yearly, attracting a great deal of interest in various fields. However, as most MIPs have been generated by relatively simple methods developed from the 1970s to the 2000s, resulting in MIPs bearing a single function, their capabilities are limited compared to those of multi-functionalised naturally occurring materials. Proteins are biosynthesised through multiple steps, including fabrication of peptide backbone and subsequent post-translational modifications that introduce additional functionalities, finally producing the mature protein. Post-imprinting modification (PIM) is an innovative strategy for generating MIPs analogous to biosynthetic proteins. New functionalities are introduced, in a site-directed manner, into a molecular imprinted cavity. Monomer residues in the cavity are chemically modified to incorporate new features, such as on/off switching of binding activity, fluorescence signalling, photoresponsivity, and finely tuned binding characteristics. In this Feature Article, we provide an overview of multifunctional MIPs prepared via PIMs developed earlier and the currently used state-of-the-art ones.

    Royal Society of Chemistry, 2018年, Chemical Communications, 54 (49), 6243 - 6251, 英語

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    研究論文(学術雑誌)

  • Sunayama, H., Kitayama, Y., Takeuchi, T.

    2018年, Journal of Molecular Recognition, 31 (3), e2633

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    研究論文(学術雑誌)

  • Satoshi Nakai, Hirobumi Sunayama, Yukiya Kitayama, Masaki Nishijima, Takehiko Wada, Yoshihisa Inoue, Toshifumi Takeuchi

    American Chemical Society (ACS), 2017年03月07日, Langmuir, 33 (9), 2103 - 2108

    [査読有り]

    研究論文(学術雑誌)

  • Eri Takano, Nobuaki Shimura, Takeshi Akiba, Yukiya Kitayama, Hirobumi Sunayama, Koichi Abe, Kazunori Ikebukuro, Toshifumi Takeuchi

    The authors describe a pipette type of biosensor for detecting target genes and using a zinc finger protein fused to luciferase (ZF luciferase). The ZF protein binds to a specific DNA sequence, and the target double-stranded (ds) DNA can be detected by monitoring the enzymatic activity of ZF luciferase. A small avidin-immobilized reaction plate is placed on a plastic pipette tip (referred to as Biologi tip). The dsDNA detection procedures are carried out by using a programmable dispensing robot equipped with a photodetector. These procedures include (a) the aspiration of an analyte to capture the biotinylated target dsDNA (a product of a polymerase chain reaction) on the small reaction plate inside the pipette tip, (b) the introduction of ZF luciferase and luciferin into the pipette tip, and (c) migration of the pipette tip to the detection port to measure bioluminescence on the small reaction plate. The emission originating from luciferase activity is observed on the reaction plate containing immobilized biotin-tagged target dsDNA, whereas plates containing non-target or biotinylated single-stranded DNA only do not yield a signal. The intensity of emission increases proportionally to the concentration of dsDNA, and the detection limit of the target dsDNA is as low as 62 pM. An actual genomic DNA sample from Escherichia coli O157 was successfully detected by this automatic analyzer using the Biologi tip equipped with a reaction plate. This indicates that this system has a large potential for practical applications, including in particular point-of-care analyses in hygiene control, food safety testing, and clinical diagnosis. [Figure not available: see fulltext.].

    Springer-Verlag Wien, 2017年06月01日, Microchimica Acta, 184 (6), 1595 - 1601, 英語

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    研究論文(学術雑誌)

  • Narito Suda, Hirobumi Sunayama, Yukiya Kitayama, Yuri Kamon, Toshifumi Takeuchi

    The Royal Society, 2017年08月, Royal Society Open Science, 4 (8), 170300

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    研究論文(学術雑誌)

  • Toshifumi Takeuchi, Hirobumi Sunayama

    Molecular imprinting is a template polymerization to prepare functional materials capable of molecular recognition. Molecularly imprinted polymers (MIPs) can be simply prepared by copolymerization of a template molecule conjugated with functional monomers and cross-linkers. These robust and affordable synthetic polymer receptors are expected to be alternatives to biomacromolecules such as antibodies and enzymes. MIPs bearing a single function have matured so far, whereas preparation of multi-functionalized MIPs is still problematic due to the simple preparation protocols. Recently, we have proposed a new strategy, post-imprinting modification (PIM), to introduce additional functionality into MIPs and/or to improve molecular recognition activity by post-polymerization modification within the imprinted cavities, which was inspired by post-translational modifications during biosynthesis of proteins. In this paper, we describe an overview of PIM-based multi-functional MIPs, and introduce desirable functions such as off/on switching of molecular recognition activity, fluorescent reporting function for the binding events, catalytic activity and photoresponsive activity.

    Society of Polymer Science, 2016年, Kobunshi Ronbunshu, 73 (1), 19 - 29, 日本語

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    研究論文(学術雑誌)

  • Ryo Horikawa, Hirobumi Sunayama, Yukiya Kitayama, Eri Takano, Toshifumi Takeuchi

    Inspired by biosystems, a process is proposed for preparing next-generation artificial polymer receptors with molecular recognition abilities capable of programmable site-directed modification following construction of nanocavities to provide multi-functionality. The proposed strategy involves strictly regulated multi-step chemical modifications: 1) fabrication of scaffolds by molecular imprinting for use as molecular recognition fields possessing reactive sites for further modifications at pre-determined positions, and 2) conjugation of appropriate functional groups with the reactive sites by post-imprinting modifications to develop programmed functionalizations designed prior to polymerization, allowing independent introduction of multiple functional groups. The proposed strategy holds promise as a reliable, affordable, and versatile approach, facilitating the emergence of polymer-based artificial antibodies bearing desirable functions that are beyond those of natural antibodies.

    WILEY-V C H VERLAG GMBH, 2016年10月, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 55 (42), 13023 - 13027, 英語

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    研究論文(学術雑誌)

  • Nobuo Murase, Takashi Mukawa, Hirobumi Sunayama, Toshifumi Takeuchi

    Photoresponsive molecularly imprinted nanocavities were prepared using a newly designed functional monomer bearing a photoresponsive spiropyran moiety with a carboxy group that can interact with atrazine (the template molecule), in which the spiropyran moiety was incorporated into the binding cavities. Spectrophotometric analysis confirmed that the spiropyran moiety was photoresponsive even after polymerization. The selectivity of the EDMA-based molecularly imprinted polymer (MIPEDMA) was tested to examine the binding behavior of atrazine and other agrochemicals, revealing that the atrazine-imprinted polymer can bind selectively to triazine herbicides. Photo-triggered switching of the binding activity in MIPEDMA was investigated, and the binding activity was found to decrease dramatically after UV light irradiation, suggesting that the spiropyran moiety in the binding cavities was transformed to the merocyanine form, resulting in unfavorable translocation of the carboxy group for atrazine binding. Consequently, the spiropyran-based MIPEDMA demonstrated in this study could open a way to realizing reliable photoresponsive smart materials. (C) 2016 Wiley Periodicals, Inc.

    WILEY, 2016年08月, JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS, 54 (16), 1637 - 1644, 英語

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    研究論文(学術雑誌)

  • Hirobumi Sunayama, Takeo Ohta, Atsushi Kuwahara, Toshifumi Takeuchi

    An antibiotic-imprinted cavity with two different fluorescent dyes was prepared by molecular imprinting and subsequent post-imprinting modifications (PIMs), for the readout of a specific binding event as a fluorescence signal. The fluorescent dyes were site-specifically introduced into the cavity using an orthogonal reversible bonding reaction, Schiff base formation, and a disulfide exchange reaction. The template molecule, comprising cephalexin connected to a Schiff base monomer and a disulfide monomer, was copolymerized with a crosslinker. This was followed by Schiff base hydrolysis and a disulfide exchange reaction, yielding the APO-type scaffold (PRECURSOR). Two different fluorophores, 4-formylsalicylic acid (FSA) and 4-(N, N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD), were introduced into the PRECURSOR by site-directed PIMs, yielding a fluorescent HOLO polymer. The obtained fluorescent polymer, HOLO(FSA)( Cys-DBD), was able to selectively readout the binding events as a fluorescence signal change. We found that the proposed strategy has the potential to open up a new class of synthetic materials possessing various desirable functions.

    ROYAL SOC CHEMISTRY, 2016年, JOURNAL OF MATERIALS CHEMISTRY B, 4 (44), 7138 - 7145, 英語

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    研究論文(学術雑誌)

  • Hironori Taguchi, Hirobumi Sunayama, Eri Takano, Yukiya Kitayama, Toshifumi Takeuchi

    Molecularly imprinted polymers bearing peptide fragment-based binding sites within the protein-imprinted cavities were prepared by copolymerization of the acrylated protein with 6-monoacryloyl- trehalose and 6,6'-diacryloyl-trehalose as a hydrophilic comonomer and a crosslinker respectively, followed by enzymatic decomposition of the grafted protein into the polymer matrix with pepsin, resulting in the creation of peptide fragment-based protein-binding sites.

    ROYAL SOC CHEMISTRY, 2015年, ANALYST, 140 (5), 1448 - 1452, 英語

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    研究論文(学術雑誌)

  • Takeuchi, T., Mori, T., Kuwahara, A., Ohta, T., Oshita, A., Sunayama, H., Kitayama, Y., Ooya, T.

    2014年, Angewandte Chemie - International Edition, 53 (47)

    [査読有り]

    研究論文(学術雑誌)

  • Sunayama, H., Ooya, T., Takeuchi, T.

    2014年, Chemical Communications, 50 (11)

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    研究論文(学術雑誌)

  • Hirobumi Sunayama, Toshifumi Takeuchi

    Protein-imprinted cavities bearing exchangeable domains to be used for postimprinting fluorophore introduction to transform binding events into fluorescence changes were constructed in molecularly imprinted polymer (MIPs) matrixes prepared on glass substrates. Copolymerization was performed with acrylamide, N,N'-methylenebisaclylamide, and a newly designed functional group-exchangeable monomer, ({[2-(2-methacrylamido)ethyldithio]ethylcarbamoyl}methoxy)acetic acid (MDTA), in the presence of a model basic protein, lysozyme (Lyso); MDTA can interact with Lyso and assemble close to Lyso in the resulting polymer. After removal of Lyso, followed by a disulfide reduction to cleave the (ethylcarbamoylmethoxy)acetic acid moiety from the MDTA residues, the exposed thiol groups within the imprinted cavities were modified by aminoethylpyridyldisulfide to be transformed into aminoethyl groups that function as active sites for amine-reactive fluorophores. Fluorescein isothiocyanate (FITC) was then coupled with the aminoethyl groups, yielding site specifically FITC-modified signaling imprinted cavities for Lyso binding. Because the in-cavity fluorescent labeling was achieved via a disulfide linkage, it was easy to remove, exchange, and/or replace amine-reactive fluorophores. This facilitated the screening of fluorophores to select the highest readout for binding events, replace fluorophores when photobleaching occurred, and introduce other functions. The proposed molecular imprinting process, combined with postimprinting modifications, is expected to provide an affordable route to develop multifunctional MIPs for specific detection of protein binding events.

    AMER CHEMICAL SOC, 2014年11月, ACS APPLIED MATERIALS & INTERFACES, 6 (22), 20003 - 20009, 英語

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    研究論文(学術雑誌)

  • Yuki Inoue, Atsushi Kuwahara, Kohei Ohmori, Hirobumi Sunayama, Tooru Ooya, Toshifumi Takeuchi

    Protein-imprinted polymers, capable of specific transduction of protein binding events into fluorescent signal change, were designed and synthesized by using dansyl ethylenediamine-conjugated O-acryloyl L-hydroxyproline (Hyp-En-Dans). Human serum albumin (HSA) was used as a model target protein and HSA-imprinted polymers (HSA-IP) were prepared on glass substrates. Specific fluorescence change was observed for HSA binding on the imprinted polymer thin film, whereas a weaker response was observed for other proteins, including bovine serum albumin, chymotrypsin, lysozyme, and avidin. The binding specificity was found to derive from the rigid structure of the hydrogen-bondable pyrrolidine moiety. Compared with SPR measurements, the non-specific binding caused by the polymer matrix and/or randomly located fluorescent monomer residues that did not compose specific binding sites did not contribute to the observed fluorescence change. These results revealed that the proposed protein-imprinting technique using Hyp-En-Dans could provide a highly selective protein-sensing platform, in which only specific binding events would be detected by fluorescent measurements. (C) 2013 Elsevier B.V. All rights reserved.

    ELSEVIER ADVANCED TECHNOLOGY, 2013年10月, BIOSENSORS & BIOELECTRONICS, 48, 113 - 119, 英語

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    研究論文(学術雑誌)

  • Yusuke Suga, Hirobumi Sunayama, Tooru Ooya, Toshifumi Takeuchi

    Molecularly imprinted polymers were prepared using a protein-conjugated disulfide cleavable monomer. After removing the protein by disulfide reduction, a thiol-reactive fluorophore was introduced into the thiol residue located only inside the imprinted cavity, resulting in specific transduction of the binding events into fluorescence spectral change. © The Royal Society of Chemistry 2013.

    2013年10月04日, Chemical Communications, 49 (76), 8450 - 8452, 英語

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    研究論文(学術雑誌)

  • Hirobumi Sunayama, Tooru Ooya, Toshifumi Takeuchi

    The functional monomer bearing three functional groups for protein imprinting was designed, which has a structure consisting of a polymerizable methacryloyl group, a secondary amine group for fluorescent dye conjugation by a post-imprinting treatment, and a benzoic acid moiety capable of interacting with a target protein. Lysozyme-imprinted polymer thin films were prepared on the initiator-immobilized glass substrates by radical polymerization in the presence of lysozyme, the designed functional monomer, a co-monomer(s) and a crosslinker. After the removal of lysozyme, fluorescein isothiocyanate was introduced into the secondary amine group of the functional monomer residues in the imprinted thin film as a fluorescent reporter dye (post-imprinting treatment). Lysozyme was selectively bound to the thin film with a binding constant of ca. 106M-1. Since the reporter dye can be only introduced into the binding cavity, the fluorescent response can be detected only when the guest is bound to the cavity, namely only specific binding events can be transduced as fluorescence spectral change. Compared with the SPR measurement, selective binding to the imprinted cavity can be more precisely detected by the proposed method, enabling us to prepare a new class of protein recognizable materials with the ability of the specific signal transduction of protein binding events. © 2010 Elsevier B.V.

    2010年10月, Biosensors and Bioelectronics, 26 (2), 458 - 462, 英語

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    研究論文(学術雑誌)

  • Natsuki Hayakawa, Yukiya Kitayama, Kazunori Igarashi, Yu Matsumoto, Eri Takano, Hirobumi Sunayama, Toshifumi Takeuchi

    American Chemical Society (ACS), 2022年04月13日, ACS Applied Materials & Interfaces, 14 (14), 16074 - 16081

    [査読有り]

    研究論文(学術雑誌)

  • Azusa Oshita, Hirobumi Sunayama, Toshifumi Takeuchi

    A molecularly imprinted nanocavity that binds to antibiotics and wherein successful binding is indicated by a change in fluorescence, which can detect not only antibiotics in aqueous media of various pH values, but also in meat extract samples.

    Royal Society of Chemistry (RSC), 2022年, Journal of Materials Chemistry B

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    研究論文(学術雑誌)

  • Aoi Yoshida, Yukiya Kitayama, Natsuki Hayakawa, Yuki Mizukawa, Yuya Nishimura, Eri Takano, Hirobumi Sunayama, Toshifumi Takeuchi

    Biocompatible polymer-modified gold nanocomposites of different shapes (nanoparticles, rods, and stars) were created to serve as radiation sensitizers. The therapeutic effect of the radiated nanostars proved to be the most effective.

    Royal Society of Chemistry (RSC), 2022年, Biomaterials Science, 10, 2665 - 2672

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    研究論文(学術雑誌)

  • Yukiya Kitayama, Takuya Yamada, Kentaro Kiguchi, Aoi Yoshida, Shuhei Hayashi, Hiroaki Akasaka, Kazunori Igarashi, Yuya Nishimura, Yu Matsumoto, Ryohei Sasaki, Eri Takano, Hirobumi Sunayama, Toshifumi Takeuchi

    Gold-nanoparticle-incorporated molecularly imprinted nanogels acquire stealth capabilities in vivo through protein corona regulation using intrinsic dysopsonic proteins. The composite can be used in radiation therapy to treat mouse pancreatic cancer.

    Royal Society of Chemistry (RSC), 2022年, Journal of Materials Chemistry B

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    研究論文(学術雑誌)

MISC

  • 砂山 博文, 竹内 俊文

    日本薬学会, 2019年02月, ファルマシア, 55 (2), 150 - 154, 日本語

    [招待有り]

    記事・総説・解説・論説等(学術雑誌)

  • 分子インプリント高分子の蛍光センシングへの応用 (特集 ホスト-ゲスト相互作用を基盤とした高分子材料)

    砂山 博文, 竹内 俊文

    高分子学会, 2012年06月, 高分子, 61 (6), 406 - 409, 日本語

  • Molecularly imprinted materials: Applications to fluorescent sensing systems

    Sunayama, H., Takeuchi, T.

    2012年, Kobunshi, 61 (6)

書籍等出版物

  • Encyclopedia of Polymeric Nanomaterials

    Takeuchi, T., Sunayama, H.

    分担執筆, Molecularly Imprinted Polymers, Springer, Berlin, Heidelberg, 2015年06月12日, 英語, ISBN: 9783642296475

  • Molecularly Imprinted Polymers in Biotechnology

    Takeuchi, T., Sunayama, H., Takano, E., Kitayama, Y.

    分担執筆, Chapter 4: Post-imprinting and In-Cavity Functionalization, Springer, Cham, 2015年, 英語, ISBN: 9783319207285

共同研究・競争的資金等の研究課題

  • 高密度分子集積ナノ界面による超高感度ウイルス検出

    科学技術振興機構, 戦略的創造研究推進事業(ACT-X), 神戸大学, 2020年12月 - 2023年03月, 研究代表者

  • 人工高分子レセプターによる光反応場の創製

    砂山 博文

    日本学術振興会, 科学研究費助成事業 若手研究, 若手研究, 神戸大学, 2019年04月01日 - 2021年03月31日

  • 多段階化学修飾による疎水性化合物認識情報発信型人工高分子レセプターの創製

    砂山 博文

    日本学術振興会, 科学研究費助成事業 若手研究(B), 若手研究(B), 安田女子大学, 2016年04月01日 - 2019年03月31日

    本年度もPIMによるMIPの機能化に関する検討を行った。モデル化合物として前立腺特異抗原(PSA)を用い、PIM用の機能性モノマーとして4-[2-(N-methacrylamido)ethylaminomethyl]benzoic acid (MABA)を合成した。このモノマーは相互作用部位として安息香酸部位、これと重合官能基の間にPIM部位として2級アミンを有する構造となっている。重合開始基としてbromo基、PSA固定化部位としてphenylboronic acid部位を有する混合自己組織化膜を作製し、これにPSAを固定化した。MABA、MPC(コモノマー)、MBAA(架橋剤)を10 mMリン酸緩衝液(pH 7.4)中、40℃で1時間反応させることで表面開始原子移動ラジカル重合にてポリマー薄膜を作製した。このポリマー薄膜の分子認識特性を表面プラズモン共鳴(SPR)測定装置にて検討を行ったところ、濃度依存的なSPRシグナルの増加が観察されたことからPSA結合空間が形成されていることが示唆された。また、選択性について検討を行ったところ、非標的分子の結合が多くみられた。このことからPIMとして低濃度のPSAを添加することで高親和性の結合空間を保護し、低親和性の結合空間にカルボン酸活性エステルを有するoligoethylene glycol鎖を導入するキャッピング処理を行ったところ、優選択性の大きな改善が確認された。また、アミノ基に反応活性のある蛍光分子を導入したところ蛍光分子に由来する蛍光シグナルが確認され、これにPSAを添加すると濃度依存的な蛍光強度の変化が観察された。 これらのことからPIMにより結合空間を選択的に修飾しMIPの機能を制御することにより情報発信型の高機能性材料を実現できることから、本研究における要素技術が実現可能であることが示された。

  • レチノール選択的分子インプリントポリマーを用いた肉牛品質検査法の開発

    砂山博文

    国立研究開発法人科学技術振興機構, 研究成果展開事業 マッチングプランナープログラム, 探索試験, 神戸大学・安田女子大学, 2015年10月 - 2016年09月, 研究代表者