タンパク質のかたちと機能を化学の力でつくりだす。

From Folding Reagents to Catalysts: Spatially Organized Diselenide–Cyclodextrins Enable Catalytic Oxidative Protein FoldingBIOMACROMOLECULES

Yuki Iwata, Shunpei Iwamoto, Hiroki Takeda, Kenta Arai*Biomacromolecules, 2026, in press. DOI: 10.1021/acs.biomac.6c01556

Beyond Folding Enzymes: A Redox-Active “Solid Chaperone” Unlocks Recyclable, HPLC-Free Oxidative Protein FoldingJACS AU

Shunpei Iwamoto, Yuya Nishizawa, Hayato Yokose, Osamu Kanie, Yosuke Okamura, Takahiro Muraoka*, Kenta Arai*JACS Au, 2026, 6, 1197–1205. DOI: 10.1021/jacsau.5c01572

An Initiator-Free Electrochemical Approach to Radical Thiol–Ene Coupling in a Microfluidic Reactor

Kakeru Yamamoto, Kenta Arai*Molecules, 2026, 31, 429. DOI: 10.3390/molecules31030429

小胞体内で織り成されるジスルフィド結合形成ネットワーク：協同的酵素機構とその模倣によるタンパク質生産効率向上の可能性REVIEW

岩本駿平、荒井堅太*（総説）東海大学先進生命科学研究所 2025年度紀要, 2026, 10, 32–37.

Ca²⁺-driven PDIA6 biomolecular condensation ensures proinsulin foldingNAT. CELL BIOL.

Young-Ho Lee, Tomohide Saio, Mai Watabe, Motonori Matsusaki, Shingo Kanemura, Yuxi Lin, Taro Mannen, Tsubura Kuramochi, Yuka Kamada, Katsuya Iuchi, Michiko Tajiri, Kotono Suzuki, Yan Li, Yunseok Heo, Kotone Ishii, Kenta Arai, Kazunori Ban, Mayuko Hashimoto, Shuichiro Oshita, Satoshi Ninagawa, Yoshikazu Hattori, Hiroyuki Kumeta, Airu Takeuchi, Shinji Kajimoto, Hiroya Abe, Eiichiro Mori, Takahiro Muraoka, Takakazu Nakabayashi, Satoko Akashi, Tsukasa Okiyoneda, Michele Vendruscolo, Kenji Inaba, Masaki OkumuraNature Cell Biology, 2025, 27, 1952–1964. DOI: 10.1038/s41556-025-01794-8

Metal-Responsive Up-Regulation of Bifunctional Disulfides for Suppressing Protein Misfolding and Promoting Oxidative FoldingANGEW. CHEM.

Keita Mori, Tsubura Kuramochi, Motonori Matsusaki, Yuki Hashiguchi, Masaki Okumura, Tomohide Saio, Yoshiaki Furukawa, Kenta Arai, Takahiro MuraokaAngew. Chem. Int. Ed., 2025, 64, e202502187. DOI: 10.1002/anie.202502187

Ca²⁺-triggered allosteric catalysts crosstalk with cellular redox system through their foldase- and reductase-like activities

Rumi Mikami, Yuhei Sato, Shingo Kanemura, Takahiro Muraoka, Masaki Okumura, Kenta Arai*Communications Chemistry, 2025, 8, 74. DOI: 10.1038/s42004-025-01466-6

ER Oxidoreductin 1-Like Activity of Cyclic Diselenides Drives Protein Disulfide Isomerase in an Electron Relay System

Rumi Mikami, Yuya Nishizawa, Yuki Iwata, Shingo Kanemura, Masaki Okumura*, Kenta Arai*ChemBioChem, 2025, 26, e202400739. DOI: 10.1002/cbic.202400739

生体酵素が指し示す酸化的フォールディング触媒の設計指針REVIEW

三神瑠美、荒井堅太*（総説）東海大学先進生命科学研究所 2023年度紀要, 2024, 8, 26–31.

Seleno-relaxin analogues: Effect of internal and external diselenide bonds on the foldability and a fibrosis-related factor of endometriotic stromal cells

Yuri Satoh, Yosuke Ono, Rikana Takahashi, Hidekazu Katayama, Michio Iwaoka, Osamu Yoshino, Kenta Arai*RSC Chem. Biol., 2024, 5, 729–737. DOI: 10.1039/d4cb00095a

Diselenide-bond replacement of the external disulfide bond of insulin increases its oligomerization leading to sustained activityCOMMUN. CHEM.

Kenta Arai*†, Masaki Okumura†, Young-Ho Lee†, Hidekazu Katayama, Kenji Mizutani, Yuxi Lin, Sam-Yong Park, Kaichiro Sawada, Masao Toyoda, Hironobu Hojo, Kenji Inaba, Michio Iwaoka* (†equal contribution)Communications Chemistry, 2023, 6, Article 258. DOI: 10.1038/s42004-023-01056-4

Resin-supported cyclic telluride as a heterogeneous promoter of disulfide formation under solid–liquid biphasic conditionsFRONT COVER

Yuya Nishizawa†, Yuri Satoh†, Osamu Kanie, Kenta Arai* (†equal contribution)New J. Chem., 2023, 47, 18537–18546. DOI: 10.1039/D3NJ02646A

Semi-enzymatic acceleration of oxidative protein folding by N-methylated heteroaromatic thiols

Shunsuke Okada†, Yosuke Matsumoto†, Rikana Takahashi, Kenta Arai, Shingo Kanemura, Masaki Okumura*, Takahiro Muraoka* (†equal contribution)Chem. Sci., 2023, 14, 7630–7636.

インスリンスーパーファミリーに属するヒトリラキシン-2の生理機能と応用REVIEW

佐藤有里、荒井堅太*（総説）東海大学先進生命科学研究所 2022年度紀要, 2023, 7, 1–6.

Modeling Type-1 Iodothyronine Deiodinase with Peptide-Based Aliphatic Diselenides: Potential Role of Highly Conserved His and Cys Residues as a General Acid CatalystHOT PAPER

Kenta Arai*, Haruka Toba, Nozomi Yamamoto, Mao Ito, Rumi MikamiChem. Eur. J., 2023, 29, e202202387. DOI: 10.1002/chem.202202387

Small Organoselenium Catalysts as a Potential Manipulator for Redox Homeostasis and ProteostasisBOOK

Kenta AraiChapter 25 in Chalcogen Chemistry: Fundamentals and Applications (ed. V. Lippolis, C. Santi, E. J. Lenardão, A. L. Braga), The Royal Society of Chemistry, 2023, pp. 648–665. DOI: 10.1039/BK9781839167386-00648

S-Denitrosylase-like Activity of Cyclic Diselenides Conjugated with Xaa-His Dipeptide: Role of Proline Spacer as a Key Activity BoosterFRONT COVER

Rumi Mikami, Shunsuke Tsukagoshi, Yoshiki Oda, Kenta Arai*ChemBioChem, 2022, 23(24), e202100394. DOI: 10.1002/cbic.202100394

Redox Chemistry of Selenols and Diselenides as Potential Manipulators for Structural Maturation of Peptides and ProteinsREVIEW

Kenta AraiMetallomics Research, 2022. metallomicsresearch.brte.org/journal/mr202206/

Abnormal Enhancement of Protein Disulfide Isomerase-like Activity of a Cyclic Diselenide Conjugated with a Basic Amino Acid by Inserting a Glycine Spacer

Rumi Mikami, Shunsuke Tsukagoshi, Kenta Arai*Biology, 2021, 10, 1090. DOI: 10.3390/biology10111090

Glutathione peroxidase-like functions of 1,2-diselenane-4,5-diol and its amphiphilic derivatives: Switchable catalytic cycles depending on peroxide substrates

Kenta Arai*, Yuumi Sato, Ikumi Nakajima, Manami Saito, Moeka Sasaki, Akiko Kanamori, Michio IwaokaBioorg. Med. Chem., 2021, 29, 115866. DOI: 10.1016/j.bmc.2020.115866

Flexible Folding: Disulfide-Containing Peptides and Proteins Choose the Pathway Depending on the EnvironmentsREVIEW

Kenta Arai, Michio Iwaoka*Molecules, 2021, 26(1), 195. DOI: 10.3390/molecules26010195

Relaxin-2 May Suppress Endometriosis by Reducing Fibrosis, Scar Formation, and Inflammation

Osamu Yoshino*, Yosuke Ono, Masako Honda, Kyoko Hattori, Erina Sato, Takehiro Hiraoka, Masami Ito, Mutsumi Kobayashi, Kenta Arai, Hidekazu Katayama, Hiroyoshi Tsuchida, Kaori Yamada-Nomoto, Shunsuke Iwahata, Yoshiyuki Fukushi, Shinichiro Wada, Haruko Iwase, Kaori Koga, Yutaka Osuga, Michio Iwaoka, Nobuya UnnoBiomedicines, 2020, 8, 467. DOI: 10.3390/biomedicines8110467

Basic amino acid conjugates of 1,2-diselenan-4-amine with protein disulfide isomerase-like functions as a manipulator of protein quality controlVIP · COVER

Shunsuke Tsukagoshi, Rumi Mikami, Kenta Arai*Chem. Asian J., 2020, 15, 2646–2652. DOI: 10.1002/asia.202000682

Modeling Thioredoxin Reductase-like Activity Using Cyclic Selenenyl Sulfides: Participation of an NH···Se Hydrogen Bond through Stabilization of the Mixed Se–S IntermediateBACK COVER

Kenta Arai, Takahiko Matsunaga, Haruhito Ueno, Nozomi Akahoshi, Yuumi Sato, Gaurango Chakrabarty, Govindasamy Mugesh*, Michio Iwaoka*Chem. Eur. J., 2019, 25, 12751–12760. DOI: 10.1002/chem.201902230

Cyclic telluride reagents with remarkable glutathione peroxidase-like activity for purification-free synthesis of highly pure organodisulfidesBACK COVER

Kenta Arai*, Yuui Osaka, Masahiro Haneda, Yuumi SatoCatal. Sci. Technol., 2019, 9, 3647–3655. DOI: 10.1039/C9CY00562E

Coupling effects of thiol and urea-type groups for promotion of oxidative protein folding

Shunsuke Okada†, Motonori Matsusaki†, Kenta Arai, Yuji Hidaka, Kenji Inaba, Masaki Okumura, Takahiro Muraoka* (†equal contribution)Chem. Commun., 2019, 55, 759–762.

Oxidative Protein Folding Using trans-3,4-Dihydroxyselenolane OxideBOOK

Kenta Arai, Michio Iwaoka*Chapter 14 in Functional Disulfide Bonds (Methods in Molecular Biology), Springer, 2019.

Characterization and Optimization of Two-Chain Folding Pathways of Insulin via Native Chain AssemblyCOMMUN. CHEM.

Kenta Arai†, Toshiki Takei†, Reina Shinozaki, Masato Noguchi, Shouta Fujisawa, Hidekazu Katayama, Luis Moroder, Setsuko Ando, Masaki Okumura, Kenji Inaba, Hironobu Hojo*, Michio Iwaoka* (†equal contribution)Communications Chemistry, 2018, 1, Article 26. DOI: 10.1038/s42004-018-0024-0

Protein Folding by Water-Soluble Cyclic Diselenides with Novel Oxidoreductase and Isomerase Activities

Kenta Arai, Haruhito Ueno, Yuki Asano, Gaurango Chakrabarty, Shingo Shimodaira, Govindasamy Mugesh*, Michio Iwaoka*ChemBioChem, 2018, 19, 207–211.

Mechanism of radioprotection by dihydroxy-1-selenolane (DHS): Effect of fatty acid conjugation and role of glutathione peroxidase (GPx)

Prachi Verma, Amit Kunwar, Kenta Arai, Michio Iwaoka, K. Indira PriyadarsiniBiochimie, 2018.

Preparation of Selenoinsulin as a Long-Lasting Insulin AnalogANGEW. CHEM.

Kenta Arai†, Toshiki Takei†, Masaki Okumura†, Satoshi Watanabe†, Yuta Amagai, Yuya Asahina, Luis Moroder, Hironobu Hojo*, Kenji Inaba*, Michio Iwaoka* (†equal contribution)Angew. Chem. Int. Ed., 2017, 56, 5522–5526. DOI: 10.1002/anie.201701654

Rapid Electrochemical Conversion of Thiol and Disulfide into Difluoro- and Trifluoromethyl Thioethers in a Microfluidic Reactor

Kenta Arai*, Setsura Ueda, Sayaka TamuraCurr. Green Chem., 2017, 4, 137–143.

Selenoglutathione Diselenide: Unique Redox Reactions in the GPx-Like Catalytic Cycle and Repairing of Disulfide Bonds in Scrambled Protein

Shingo Shimodaira, Yuki Asano, Kenta Arai, Michio Iwaoka*Biochemistry, 2017, 56, 5644–5653.

Glutathione Peroxidase-Like Activity of Amino-Substituted Water-Soluble Cyclic Selenides: A Shift of the Major Catalytic Cycle in Methanol

Kenta Arai*, Ayako Tashiro, Yuui Osaka, Michio Iwaoka*Molecules, 2017, 22, 354. DOI: 10.3390/molecules22030354

Non-bonded Selenium···Heteroatom Interactions in Selenoenzyme Glutathione Peroxidase and MimicsBOOK

Michio Iwaoka*, Kenta AraiChapter 7 in Organoselenium Compounds in Biology and Medicine (RSC), 2017.

Alkyl chain modulated cytotoxicity and antioxidant activity of bioinspired amphiphilic selenolanes

Prachi Verma, Amit Kunwar, Kenta Arai, Michio Iwaoka, K. Indira PriyadarsiniToxicol. Res., 2016, 5, 434–445.

Tetrahydroselenophene. A Unique Structural Motif for Biochemical ApplicationsREVIEW

Kenta Arai, Michio IwaokaCurr. Org. Chem., 2016, 20, 155–165. DOI: 10.2174/1385272819666150724233306

Fatty Acid Conjugates of Water-Soluble (±)-trans-Selenolane-3,4-diol: Effects of Alkyl Chain Length on the Antioxidant Capacity

Michio Iwaoka, Nobukazu Sano, Ying-Yin Lin, Arisa Katakura, Masato Noguchi, Kohei Takahashi, Fumio Kumakura, Kenta Arai, Beena G. Singh, Amit Kunwar, K. Indira PriyadarsiniChemBioChem, 2015, 16, 1226–1234.

Effects of Ring Size and Polar Functional Groups on the Glutathione Peroxidase-Like Antioxidant Activity of Water-Soluble Cyclic Selenides

Kenta Arai, Fumio Kumakura, Motoi Takahira, Natsumi Sekiyama, Nozomi Kuroda, Toshiki Suzuki, Michio IwaokaJ. Org. Chem., 2015, 80, 5633–5642. DOI: 10.1021/acs.joc.5b00544

An Amphiphilic Selenide Catalyst Behaves Like a Hybrid Mimic of Protein Disulfide Isomerase and Glutathione Peroxidase 7BACK COVER

Kenta Arai, Kenji Moriai, Akinobu Ogawa, Michio IwaokaChem. Asian J., 2014, 9, 3464–3471. DOI: 10.1002/asia.201402726

Rapid Electrochemical Deprotection of the Isonicotinyloxycarbonyl Group from Carbonates and Thiocarbonates in a Microfluidic Reactor

Kenta Arai, Thomas WirthOrg. Process Res. Dev., 2014, 18, 1377–1381.

Difluoro- and Trifluoromethylation of Electron-deficient Alkenes in an Electrochemical Microreactor

Kenta Arai, Kevin Watts, Thomas WirthChemistryOpen, 2014, 3, 23–28.

Model Study Using Designed Selenopeptides on the Importance of the Catalytic Triad for the Antioxidative Functions of Glutathione Peroxidase

Toshiki Takei, Yoshiko Urabe, Yuya Asahina, Hironobu Hojo, Takeshi Nomura, Kenichi Dedachi, Kenta Arai, Michio IwaokaJ. Phys. Chem. B, 2014, 118, 492–500.

Reinvestigation of the Oxidative Folding Pathways of Hen Egg White Lysozyme: Switching of the Major Pathways by Temperature Control

Kenta Arai, Wataru Shibagaki, Reina Shinozaki, Michio IwaokaInt. J. Mol. Sci., 2013, 14, 13194–13212.

A Water-Soluble Selenoxide Reagent as a Useful Probe for the Reactivity and Folding of Polythiol Peptides

Kenta Arai, Masato Noguchi, Beena G. Singh, K. Indira Priyadarsini, Katsuhiko Fujio, Yurika Kubo, Kyoko Takayama, Setsuko Ando, Michio IwaokaFEBS Open Bio, 2013, 3, 55–64.

From Sulfur to Selenium. A New Research Arena in Chemical Biology and Biological ChemistryREVIEW

Michio Iwaoka, Kenta AraiCurr. Chem. Biol., 2013, 7, 2–24. DOI: 10.2174/2212796811307010002

Kinetic and Thermodynamic Analysis of the Conformational Folding Process of SS-Reduced Bovine Pancreatic Ribonuclease A Using a Selenoxide Reagent with High Oxidizing Ability

Kenta Arai, Fumio Kumakura, Michio IwaokaFEBS Open Bio, 2012, 2, 60–70.

Antioxidative Glutathione Peroxidase Activity of Selenoglutathione

Sari Yoshida, Fumio Kumakura, Itsuki Komatsu, Kenta Arai, Yuko Onuma, Hironobu Hojo*, Beena G. Singh, K. Indira Priyadarsini, Michio Iwaoka*Angew. Chem. Int. Ed., 2011, 50, 2125–2128.

Rapid and Quantitative Disulfide Bond Formation for a Polypeptide Chain Using a Cyclic Selenoxide Reagent in an Aqueous MediumVIP · COVER

Kenta Arai, Kenichi Dedachi, Michio Iwaoka*Chem. Eur. J., 2011, 17, 481–485. DOI: 10.1002/chem.201002742

Characterization of Kinetic and Thermodynamic Phases in the Pre-Folding Process of Bovine Pancreatic Ribonuclease A Coupled with Fast SS Formation and SS Reshuffling

Kenta Arai, Fumio Kumakura, Michio IwaokaBiochemistry, 2010, 49, 10535–10542.