論文 - 戸嶋　一敦

Photo-induced glycosylation using edible polyphenol ellagic acid

Hidenari Shigeta, Satomi Goi, DAISUKE TAKAHASHI, *Kazunobu Toshima

Carbohydrate Research （Elsevier ）  552   109461 2025年03月

研究論文（学術雑誌）, 査読有り

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Creation of a New Macrolide Antibiotic against Non-tuberculous Mycobacterium Using Late-stage Boron-mediated Aglycon Delivery

Yuka Isozaki, Takumi Makikawa, Kosuke Kimura, Daiki Nishihara, Fujino, Yoshikazu Tanaka, Chigusa Hayashi, Yoshimasa Ishizaki, *Masayuki Igarashi, *Takeshi Yokoyama, *Kazunobu Toshima, *DAISUKE TAKAHASHI

Science Advances （American Association for the Advancement of Science）  11 （ 10 ） eadt2352 2025年03月

研究論文（学術雑誌）, 最終著者, 責任著者, 査読有り

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A novel porphyrin-based theranostic agent activated by cysteine over-expressed in cancer cells shows promise for tumour-targeted monitoring and phototherapy

Fumihisa Ishida, Satoe Moriya, DAISUKE TAKAHASHI, *Kazunobu Toshima

Bioorganic & Medicinal Chemistry （Elsevier）  121   118131 2025年02月

研究論文（学術雑誌）, 査読有り

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Synthesis of Low-Molecular-Weight Fucoidan Analogue and Its Inhibitory Activities against Heparanase and SARS-CoV-2 Infection

Aoi Sugimoto, Tatsuki Koike, Yuya Kuboki, Sumika Komaba, Shuhei Kosono, Maniyamma Aswathy, Itsuki Anzai, Tokiko Watanabe, *Kazunobu Toshima, *DAISUKE TAKAHASHI

Angewandte Chemie International Edition （Wiley-VCH）  64 （ 6 ） e202411760 2024年10月

研究論文（学術雑誌）, 最終著者, 責任著者, 査読有り

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A novel photosensitizer based on hypocrellin B activated by cysteine over-expressed in cancer cells

Fumihisa Ishida, Rikuto Onishi, DAISUKE TAKAHASHI, *Kazunobu Toshima

Organic & Biomolecular Chemistry （Royal Society of Chemistry）  22   7187 - 7193 2024年08月

研究論文（学術雑誌）, 査読有り

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Designed Mannosylerythritol Lipid Analogues Exhibiting both Selective Cytotoxicity against Human Skin Cancer Cells and Recovery Effects on Damaged Skin Cells

Jikun Meng, Chihiro Yasui, Mai Shida, Kazunobu Toshima, *DAISUKE TAKAHASHI

Chemistry A European Journal 2024年05月

研究論文（学術雑誌）, 責任著者, 査読有り

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Photo-Induced Glycosylation Using the Edible Polyphenol Curcumin

Satomi Goi, Hidenari Shigeta, DAISUKE TAKAHASHI, *Kazunobu Toshima

（Organic & Biomolecular Chemistry ）  2024年05月

最終著者, 責任著者, 査読有り

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Discovery of a Novel Photosensitizer Based on the Enediyne Antibiotic N1999A2 and Its Application as a Glutathione-Activatable Theranostic Agent

Kotono Matsunaga, Minami Takahashi, Tugumi Kagaya, DAISUKE TAKAHASHI, *Kazunobu Toshima

Bulletin of the Chemical Society of Japan 97卷 （ 5号 ） uoae057頁  2024年05月

研究論文（学術雑誌）, 最終著者, 責任著者, 査読有り

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Synthesis and Immunological Evaluation of Escherichia coli O1- Derived Oligosaccharide–Protein Conjugates toward Avian Pathogenic Escherichia coli O1 Vaccine Development

Katsunori Seki, Takumi Makikawa, *Kazunobu Toshima, *DAISUKE TAKAHASHI

Synthesis （Georg Thieme Verlag KG ）  56巻 （ 06号 ） 953頁 - 965頁 2023年08月

研究論文（学術雑誌）, 共著, 責任著者, 査読有り,  ISSN  0039-7881

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Abstract
Avian pathogenic Escherichia coli O1 (APEC O1) is a pathogenic bacterium that causes significant economic losses in the poultry industry and raises concerns about zoonotic infections. The development of effective vaccines against APEC O1 is essential due to antibiotic resistance and the potential for severe symptoms in both chickens and humans. In this context, we have been focusing on the O1A, O1B, and O1C antigen structures derived from E. coli O1 lipopolysaccharide (LPS). In this study, the first synthesis of the pentasaccharide repeating units of the O1B and O1C antigens was successfully achieved. The synthesis and immunological evaluation of their conjugates with bovine serum albumin (BSA) were conducted. Only the O1A-pentasaccharide structure is a glycotope candidate for APEC O1. Keyhole limpet hemocyanin (KLH)–O1A-pentasaccharide conjugate was also synthesized, and its immunogenicity was evaluated by the ELISA assay. The efficient production of antibodies capable of binding to both APEC O1 LPS and the O1A-pentasaccharide structure was observed, indicating that O1A-pentasaccharide is a promising vaccine candidate against APEC O1.

Regioselective and Stereospecific β-Arabinofuranosylation by Boron-Mediated Aglycon Delivery

Inaba K., Naito Y., Tachibana M., Toshima K., Takahashi D.

Angewandte Chemie - International Edition （Angewandte Chemie - International Edition ）  2023年07月

共著, 責任著者, 査読有り,  ISSN  14337851

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Regio- and stereoselective formation of the 1,2-cis-furanosidic linkage has been in great demand for efficient synthesis of biologically active natural glycosides. In this study, we developed a regioselective and β-stereospecific d-/l-arabinofuranosylation promoted by a boronic acid catalyst under mild conditions. The glycosylations proceeded smoothly for a variety of diols, triols, and unprotected sugar acceptors to give the corresponding β-arabinofuranosides (β-Arbf) in high yields with complete β-stereoselectivity and high regioselectivity. The regioselectivity was completely reversed depending on the optical isomerism of the donor used and was predictable a priori using predictive models. Mechanistic studies based on DFT calculations revealed that the present glycosylation occurs through a highly dissociative concerted SNi mechanism. The usefulness of the glycosylation method was demonstrated by the chemical synthesis of trisaccharide structures of arabinogalactan fragments.

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Photoinduced Glycosylation Using a Diarylthiophene as an Organo Lewis Photoacid Catalyst

Otani N., Higashiyama K., Sakai H., Hasobe T., Takahashi D., Toshima K.

European Journal of Organic Chemistry （European Journal of Organic Chemistry）  26巻  2023年04月

研究論文（学術雑誌）, 最終著者, 責任著者, 査読有り,  ISSN  1434193X

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Here reports an photoinduced glycosylation of trichloroacetimidate donors and several alcohols using 3,11-dimethoxydinaphthothiophene as an organo Lewis photoacid catalyst upon long-wavelength UV-LED light (385 nm) irradiation. The reaction proceeded under mild reaction conditions smoothly to give the corresponding glycosides in good to high yields. In addition, the present glycosylation method was applicable to a wide range of trichloroacetimidate donors and acceptors. Furthermore, the dinaphthothiophene catalyst could be recovered and reused without any loss of efficiency. Moreover, this glycosylation method was applied successfully to the total synthesis of a biologically active natural product, cholesteryl 6-O-myristoyl-α-glucoside.

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Destabilization of vitelline membrane outer layer protein 1 homolog (VMO1) by <i>C</i> ‐mannosylation

Satoshi Yoshimoto, Takehiro Suzuki, Naoki Otani, DAISUKE TAKAHASHI, Kazunobu Toshima, Naoshi Dohmae, Siro Simizu

FEBS Open Bio （Wiley）  13 （ 3 ） 490 - 499 2023年01月

査読有り,  ISSN  2211-5463

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Photoinduced Glycosylation Using a Diarylthiophene as an Organo Lewis Photoacid Catalyst

Otani N., Higashiyama K., Sakai H., Hasobe T., Takahashi D., Toshima K.

European Journal of Organic Chemistry （European Journal of Organic Chemistry）  2023年

最終著者, 責任著者, 査読有り,  ISSN  1434193X

　概要を見る

Here reports an photoinduced glycosylation of trichloroacetimidate donors and several alcohols using 3,11-dimethoxydinaphthothiophene as an organo Lewis photoacid catalyst upon long-wavelength UV-LED light (385 nm) irradiation. The reaction proceeded under mild reaction conditions smoothly to give the corresponding glycosides in good to high yields. In addition, the present glycosylation method was applicable to a wide range of trichloroacetimidate donors and acceptors. Furthermore, the dinaphthothiophene catalyst could be recovered and reused without any loss of efficiency. Moreover, this glycosylation method was applied successfully to the total synthesis of a biologically active natural product, cholesteryl 6-O-myristoyl-α-glucoside.

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Synthesis of Mannosylerythritol Lipid Analogues and their Self-Assembling Properties, Recovery Effects on Damaged Skin Cells, and Antibacterial Activity

Kondo T., Yasui C., Miyajima I., Banno T., Asakura K., Fukuoka T., Ushimaru K., Koga M., Saika A., Morita T., Takahashi Y., Hayashi C., Igarashi M., Takahashi D., Toshima K.

Chemistry - A European Journal （Chemistry - A European Journal）  28 （ 55 ）  2022年10月

最終著者, 責任著者, 査読有り,  ISSN  09476539

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Synthesis of three types of purpose-designed mannosylerythritol lipid (MEL)-D analogues with decanoyl groups (C10), β-GlcEL-D, α-GlcEL-D, and α-MEL-D, was accomplished utilizing our boron-mediated aglycon delivery (BMAD) methods. Their self-assembling properties, recovery effects on damaged skin cells, and antibacterial activity were evaluated. It was revealed, for the first time, that α-GlcEL-D and α-MEL-D only generated giant vesicles, indicating that slight differences in the steric configuration of an erythritol moiety and fatty acyl chains affect the ability to form vesicles. Analogue α-MEL-D exhibited significant recovery effects on damaged skin cells. Furthermore, α-MEL-D exhibited antibacterial activity as high as that for MEL-D, indicating that α-MEL-D is a promising artificial sugar-based material candidate for enhancing the barrier function of the stratum corneum, superior to a known cosmetic ingredient, and possesses antibacterial activity.

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Efficient Strategy for the Preparation of Chemical Probes of Biologically Active Glycosides Using a Boron-Mediated Aglycon Delivery (BMAD) Method

Kimura K., Yasunaga T., Makikawa T., Takahashi D., Toshima K.

Bulletin of the Chemical Society of Japan （Bulletin of the Chemical Society of Japan）  95 （ ７ ） 1075 - 1082 2022年07月

査読有り,  ISSN  00092673

　概要を見る

Development of an efficient method for the analysis and identification of the target proteins with which biologically active glycosides directly interact is highly desirable in many research fields. In this article, we report an efficient strategy for the preparation of chemical probes of biologically active glycosides using a reaction sequence of i) a boron-mediated aglycon delivery (BMAD) with an N3-functionalized 1,2-anhydroglu-cose donor, ii) deprotection, and iii) strain-promoted azidealkyne cycloaddition. Using the synthesized chemical probes, we successfully demonstrated that the target proteins of a cardiac glycoside, lanatoside C (1), can be visualized and identified in human colon cancer HCT116 cells.

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Self-Assembling Properties and Recovery Effects on Damaged Skin Cells of Chemically Synthesized Mannosylerythritol Lipids

T. Kondo ., C. Yasui ., T. Banno ., K. Asakura ., T. Fukuoka ., K. Ushimaru., M. Koga., H. Minamikawa., A. Saika., T. Morita., D. Takahashi ., K. Toshima.

ChemBioChem （ChemBioChem）  23 （ 2 ） e202100631 2022年01月

最終著者, 責任著者, 査読有り,  ISSN  14394227

　概要を見る

Mannosylerythritol lipids (MELs), which are one of the representative sugar-based biosurfactants (BSs) produced by microorganisms, have attracted much attention in various fields in the sustainable development goals (SDGs) era. However, they are inseparable mixtures with respect to the chain length of the fatty acids. In this study, self-assembling properties and structure-activity relationship (SAR) studies of recovery effects on damaged skin cells using chemically synthesized MELs were investigated. It was revealed, for the first time, that synthetic and homogeneous MELs exhibited significant self-assembling properties to form droplets or giant vesicles. In addition, a small difference in the length of the fatty acid chains of the MELs significantly affected their recovery effects on the damaged skin cells. MELs with medium or longer length alkyl chains exhibited much higher recovery effects than that of C18-ceramide NP.

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Hypocrellin B-based activatable photosensitizers for specific photodynamic effects against high H<inf>2</inf>O<inf>2</inf>-expressing cancer cells

T. Kitamura., H. Nakata., D. Takahashi., K. Toshima.

Chemical Communications （Chemical Communications）  58 （ 2 ） 242 - 245 2022年01月

最終著者, 責任著者, 査読有り,  ISSN  13597345

　概要を見る

A novel tumor-related biomarker, a H2O2-activatable photosensitizer4based on the 1,3-dicarbonyl enol moieties of hypocrellin B (3), was designed and synthesized. The photosensitizer4showed a blue-shifted absorption band compared with3, and showed negligible photosensitizing ability without H2O2. However, the release of3from4by the reaction with H2O2regenerated the photosensitizing ability. Furthermore,4exhibited selective and effective photo-cytotoxicity against high H2O2-expressing cancer cells upon photo-irradiation with 660 nm light, which is inside the phototherapeutic window.

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Synthesis of low-molecular weight fucoidan derivatives and their binding abilities to SARS-CoV-2 spike proteins

T. Koike ., A. Sugimoto., S. Kosono ., S. Komaba ., Y. Kanno .,T. Kitamura., I. Anzai ., T. Watanabe ., D. Takahashi ., K. Toshima

RSC Medicinal Chemistry （RSC Medicinal Chemistry）  12 （ 12 ） 2016 - 2021 2021年12月

最終著者, 責任著者, 査読有り,  ISSN  26328682

　概要を見る

Fucoidan derivatives10-13, whose basic sugar chains are composed of repeating α(1,4)-linkedl-fucopyranosyl residues with different sulfation patterns, were designed and systematically synthesized. A structure-activity relationship (SAR) study examined competitive inhibition by thirteen fucoidan derivatives against heparin binding to the SARS-CoV-2 spike (S) protein. The results showed for the first time that10exhibited the highest inhibitory activity of the fucoidan derivatives used. The inhibitory activity of10was much higher than that of fondaparinux, the reported ligand of SARS-CoV-2 S protein. Furthermore,10exhibited inhibitory activities against the binding of heparin with several mutant SARS-CoV-2 S proteins, but was found to not inhibit factor Xa (FXa) activity that could otherwise lead to undesirable anticoagulant activity.

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Synthesis of a Pentasaccharide Repeating Unit of Lipopolysaccharide Derived from Virulent E. coli O1 and Identification of a Glycotope Candidate of Avian Pathogenic E. coli O1

Nobuya Nishi, Katsunori Seki, *Daisuke Takahashi, *Kazunobu Toshima

Angewandte Chemie - International Edition （Angewandte Chemie - International Edition）  60 （ 4 ） 1789 - 1796 2021年01月

研究論文（学術雑誌）, 査読有り,  ISSN  14337851

　概要を見る

© 2020 Wiley-VCH GmbH Avian pathogenic Escherichia coli (APEC) is a common bacterial pathogen infecting chickens, resulting in economic losses to the poultry industry worldwide. In particular, APEC O1, one of the most common serotypes of APEC, is considered problematic due to its zoonotic potential. Therefore, many attempts have been made to develop an effective vaccine against APEC O1. In fact, the lipopolysaccharide (LPS) O-antigen of APEC O1 has been shown to be a potent antigen for inducing specific protective immune responses. However, the detailed structure of the O-antigen of APEC O1 is not clear. The present study demonstrates the first synthesis of a pentasaccharide repeating unit of LPS derived from virulent E. coli O1 and its conjugate with BSA. ELISA tests using the semi-synthetic glycoconjugate and the APEC O1 immune chicken serum revealed that the pentasaccharide is a glycotope candidate of APEC O1, with great potential as an antigen for vaccine development.

This paper was press-released from Keio University. (https://www.keio.ac.jp/ja/press-releases/2020/11/16/28-76321/)
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Diboron-Catalyzed Regio- and 1,2-cis-α-Stereoselective Glycosylation of trans-1,2-Diols.

Shunpei Tomita, Masamichi Tanaka, Michitaka Inoue, Kazuki Inaba, *Daisuke Takahashi, *Kazunobu Toshima

THE JOURNAL OF ORGANIC CHEMISTRY （American Chemical Society）  85 （ 24 ） 16254 - 16262 2020年12月

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

Regio- and 1,2-cis-α-stereoselective glycosylations were investigated using 1,2-anhydroglucose donors and trans-1,2-diol sugar acceptors in the presence of a diboron catalyst. The reactions proceeded smoothly to provide the corresponding 1,2-cis-α-glycosides with consistently very high stereoselectivity and were regioselectivity controlled by the protecting groups of the acceptor. The present glycosylation method was applied successfully to the efficient synthesis of α-1,3-glucan pentasaccharide.

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