Hanaya, Kengo

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmaceutical Sciences 有機薬化学講座 (Shiba-Kyoritsu)

Position

Assistant Professor/Senior Assistant Professor
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Academic Degrees 【 Display / hide 】

  • 博士（薬学）, Tokyo University of Science, Coursework, 2012.03

    Design and Synthesis of Biomedical Tools and Metalloprotease Inhibitors Based on Chemical Properties of 8-Quinolinol and Their Sulfonates

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Papers 【 Display / hide 】

  • One-Step Maleimide-Based Dual Functionalization of Protein N-Termini.

    Kengo Hanaya, Kazuaki Taguchi, Yuki Wada, Masaki Kawano

    Angewandte Chemie International Edition (Wiley)     e202417134 2024.11

    Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted,  ISSN  14337851

    　View Summary

    Maleimide derivatives are privileged reagents for chemically modifying proteins through the Michael addition reaction with cysteine due to their selectivity, operational simplicity, and commercial availability. However, since accessible free cysteine is rarely found in natural proteins, it is highly desirable to find alternative targets to enable direct bioconjugation of proteins with maleimides. In this study, we have developed an operationally simple and straightforward method for the N-terminal modification of proteins without the need for mutagenesis via a copper(II)-mediated [3+2] cycloaddition reaction with maleimides and 2-pyridinecarboxaldehyde (2-PCA) derivatives under non-denaturing conditions at pH 6 and 37 °C in aqueous media. Our method utilizes commercially available maleimides to attach diverse functionalities to various N-terminal amino acids. We demonstrate the preparation of a ternary protein complex cross-linked at the N-termini and dually modified trastuzumab equipped with monomethyl auristatin E (MMAE), a cytotoxic agent, and a Cy5 fluorophore (MMAE-Cy5-trastuzumab). MMAE-Cy5-trastuzumab retained human epidermal growth factor receptor 2 (HER2) recognition activity and exerted cytotoxicity against HER2-positive cells. Furthermore, MMAE-Cy5-trastuzumab allowed successful visualization of HER2-positive cancer cells in mouse tumors. This straightforward method will expand the accessibility of protein conjugates with well-defined structures in a wide range of research fields.

  • Dual delivery of carbon monoxide and doxorubicin using haemoglobin-albumin cluster: proof of concept for well-tolerated cancer therapy

    Ito C., Taguchi K., Yamada T., Hanaya K., Enoki Y., Sugai T., Komatsu T., Matsumoto K.

    Journal of Materials Chemistry B 12 ( 23 ) 5600 - 5608 2024.05

    ISSN  2050750X

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    A serious concern of doxorubicin (DOX) therapy is that it causes severe adverse effects, particularly cardiotoxicity. Carbon monoxide (CO) possesses powerful cytoprotective effects against drug-induced organ injury and is expected to ameliorate DOX-induced cardiotoxicity. In this study, a dual carrier of DOX and CO (CO-HemoAct-DOX) was fabricated based on a haemoglobin-albumin cluster (HemoAct), which is a protein cluster with a haemoglobin core structure wrapped by serum albumin. CO-HemoAct-DOX was synthesised by binding CO to a haemoglobin core and covalently conjugating (6-maleimidocaproyl)hydrazone derivative of DOX to an albumin shell. The average DOX/cluster ratio was about 2.6. In the in vitro cytotoxicity assay against cancer cells, the anti-tumour activity of CO-HemoAct-DOX was 10-fold lower than that of DOX in a 2D-cultured model, whereas CO-HemoAct-DOX suppressed the growth of tumour spheroids to the same extent as DOX in the 3D-cultured model. In colon-26 tumour-bearing mice, CO-HemoAct-DOX achieved DOX delivery to the tumour site and alleviated tumour growth more effectively than DOX. Furthermore, CO-HemoAct attenuated DOX-induced cardiomyocyte atrophy in H9c2 cells and elevated the levels of cardiac biomarkers in mice exposed to DOX. These results suggest that the dual delivery of CO and DOX using HemoAct is a promising strategy as an anti-tumour agent to realise well-tolerated cancer therapy with minimal cardiotoxicity.

  • Synthesis and property of 2,2-difluoro-1,4-diazaborole

    Nakahara M., Wada Y., Kawano M., Hanaya K., Sugai T., Higashibayashi S.

    Chemistry Letters 53 ( 5 )  2024.05

    ISSN  03667022

    　View Summary

    The synthesis of 2,2-difluoro-1,4-diazaboroles was achieved through the condensation of aliphatic acyltrifluoroborates and amino-N-heteroarenes under acidic conditions. Various N-heteroarenes, including pyridine, pyrimidine, pyridazine, thiazole, and isoquinoline, were successfully employed in the reaction. Among the synthesized 2,2-difluoro-1,4-diazaboroles, the one with an isoquinoline structure exhibited the most intense light blue emission.

  • Utilization of Lipase-Catalyzed Acetylation and Deacetylation in the Synthesis of a Natural Product with a Hydroquinone Skeleton

    Sugai T., Honda K., Hashimoto R., Hanaya K., Higashibayashi S.

    Asian Journal of Organic Chemistry 13 ( 12 )  2024

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    Elaborated conditions for lipase-catalyzed preferential monoacetylation enabled the large-scale preparation of hydroquinone monoacetate. This product was then applied to the synthesis of tournefolin B, a highly oxygenated prenylated hydroquinone of plant origin (Tournefortia sarmentosa Lam.). During the course of the synthetic transformations, lipase-catalyzed deacetylation under mild conditions was demonstrated.

  • Unified short syntheses of oxygenated tricyclic aromatic diterpenes by radical cyclization with a photoredox catalyst

    Hashimoto R., Hanaya K., Sugai T., Higashibayashi S.

    Communications Chemistry (Communications Chemistry)  6 ( 1 )  2023.12

    Research paper (scientific journal), Joint Work, Accepted

    　View Summary

    The biomimetic two-phase strategy employing polyene cyclization and subsequent oxidation/substitution is an effective approach for divergent syntheses of [6-6-6]-tricyclic diterpenes. However, this strategy requires lengthy sequences for syntheses of oxygenated tricyclic aromatic abietane/podocarpane diterpenes owing to the many linear oxidation/substitution steps after cyclization. Here, we present a new synthetic route based on a convergent reverse two-phase strategy employing a reverse radical cyclization approach, which enabled the unified short syntheses of four aromatic abietane/podocarpane diterpenes and the divergent short syntheses of other related diterpenes. Oxygenated and substituted precursors for cyclization were convergently prepared through Friedel-Crafts acylation and rhodium-catalyzed site-selective iodination. Radical redox cyclization using an iridium photoredox catalyst involving neophyl rearrangement furnished the thermodynamically favored 6-membered ring preferentially. (±)-5,6-Dehydrosugiol, salvinolone, crossogumerin A, and Δ5-nimbidiol were synthesized in only 8 steps. An oxygenated cyclized intermediate was also useful for divergent derivatization to sugiol, ferruginol, saprorthoquinone, cryptomeriololide, and salvinolone.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Presentations 【 Display / hide 】

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 金属結合モチーフの構築を志向したポリペプチド化学修飾

    2024.04
    -
    2027.03

    基盤研究(C), Principal investigator

  • 一時的配向基を用いた遷移金属触媒反応によるタンパク質ペプチド結合の化学修飾

    2021.04
    -
    2024.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • ボロン酸を用いるクロスカップリング反応を基盤としたタンパク質化学修飾法の開発

    2019.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

  • スルホン酸エステルを母核とした刺激応答性リンカーの開発とプロドラッグへの応用

    2016.04
    -
    2019.03

    JAPAN SOCIETY FOR THE PROMOTION OF SCIENCE, Grant-in-Aid for Scientific Research, KENGO HANAYA, Research grant, No Setting

  • 刺激応答性リンカーの創製に向けたアミノスルホン酸エステルの分子内環化反応の開発

    2016.04
    -
    2017.03

    THE JAPAN SCIENCE SOCIETY, SASAKAWA SCIENTIFIC RESEARCH GRANT, KENGO HANAYA, Research grant, Principal investigator

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Courses Taught 【 Display / hide 】

  • STUDY OF MAJOR FIELD (ADVANCED MOLECULAR CHEMISTRY)

    2025

  • SEMINAR (ADVANCED MOLECULAR CHEMISTRY)

    2025

  • RESEARCH FOR BACHELOR'S THESIS 1

    2025

  • RESEARCH APPARATUS LABORATORY COURSE

    2025

  • PHARMACEUTICAL-ENGLISH SEMINAR

    2025

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