KEIO RESEARCHERS INFORMATION SYSTEM

Academic Degrees 【 Display / hide 】

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

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Stepwise dual N-terminal modification of proteins via nickel(II)-mediated aldol and Pictet–Spengler reactions

  Kengo Hanaya, Yuki Morimi, Shoma Usui, Kazuaki Taguchi, Yuki Wada, Masaki Kawano, Shuhei Higashibayashi, Takeshi Sugai

  Tetrahedron Chem (Elsevier)  17   100154 2026.01

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

  • Access to Document (DOI)

• Structural Elucidation of Nucleophilic Compounds through Synergistic Coordination and Hydrogen Bonding in a Metal–Organic Framework

  Nakagawa T., Wada Y., Chan B., Baba T., Hanaya K., Koseki Y., Asano R., Aoki K., Usov P.M., Kawano M.

  Journal of the American Chemical Society 147 ( 32 ) 29013 - 29025 2025.08

  ISSN  00027863

  　View Summary

  This study presents the development of a novel metal–organic framework (MOF) denoted as APF-80, suitable for the structural analysis of nucleophilic compounds that have traditionally been challenging to analyze using the crystalline sponge method. It was synthesized using a new mixed-substituent hexaazaphenalene ligand (344-TPHAP) featuring both 3-pyridyl and 4-pyridyl groups. This framework demonstrated remarkable stability toward nucleophilic molecules, which could be captured inside the pores through a synergistic combination of coordination and hydrogen-bonding interactions. APF-80 was successfully applied to determine the structures of 12 bioactive molecules, including naturally occurring alkaloids and pharmaceutical compounds. The host–guest interaction modes observed inside the resulting structures were classified into five distinct types. Binding energy calculations revealed that the guest site energies positively correlated with the crystallographic occupancies and the corresponding interaction types. This multimodal capture mechanism enabled the precise structural analysis of nucleophilic compounds under mild conditions, expanding the scope of molecules that can be analyzed by the crystalline sponge method.

  • Access to Document (DOI)

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

  Kengo Hanaya, Kazuaki Taguchi, Yuki Wada, Masaki Kawano

  Angewandte Chemie International Edition (Wiley)  64 ( 5 ) 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.

  • Access to Document (DOI)

• 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

  　View Summary

  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.

  • Access to Document (DOI)

• 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.

  • Access to Document (DOI)

display all >>

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

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

• Development of a selective fluorescent probe for quantifying sperm protamine for the rapid diagnosis of male infertility

  Hanaya, Kengo

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2024

• Chemical modification of polypeptides via metal-mediated reaction

  Hanaya, Kengo

  科学研究費補助金研究成果報告書 2023

• Dual functionalization of N-termini of polypeptides

  Hanaya, Kengo

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2023

• Development of single-step N-terminal modification via copper(II)-mediated aldol reaction

  Hanaya, Kengo

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2022

• Metal-mediated protein modification with transient directing groups

  Hanaya, Kengo

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2021

display all >>

Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• One-step dual functionalization of protein N-termini

  花屋 賢悟, 田口 和明, 和田 雄貴, 河野 正

  [Domestic presentation] 

  2026.03

  , 

  Oral presentation (general)

• アミノ酸-金属イオン相互作用を活用したポリペプチドＮ末端化学修飾法の開発

  花屋賢悟

  [Domestic presentation]  第69回日本薬学会関東支部大会, 

  2025.09

  , 

  Oral presentation (invited, special)

• Maleimide-based functionalization of protein N-termini

  花屋賢悟, 田口和明, 和田雄貴, 河野正規

  [Domestic presentation]  日本ケミカルバイオロジー学会　第19回年会, 

  2025.06

  , 

  Poster presentation

• Selective modification of tryptophan in polypeptides via oxidative coupling using in-situ-generated hypervalent iodine species in acidic aqueous media

  花屋賢悟, 渡辺俊介, 和田雄貴, 河野正規, 東林修平, 須貝威

  [Domestic presentation]  日本薬学会第144年会 (パシフィコ横浜) , 

  2024.03

  , 

  Oral presentation (general)

• N-terminal modification of polypeptides via metal-mediated aldol reaction

  花屋賢悟、和田雄貴、河野正規、田口和明、松元一明、東林修平、須貝威

  [Domestic presentation]  日本化学会第104春季年会(2024) (日本大学理学部　船橋キャンパス) , 

  2024.03

  , 

  Oral presentation (general)

display all >>

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

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

display all >>

Awards 【 Display / hide 】

Awards 【 Display / hide 】

• 令和7年度日本薬学会関東支部奨励賞

  2025.09

  Type of Award： Award from Japanese society, conference, symposium, etc.

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• ADVANCED MEDICINAL AND ORGANIC CHEMISTRY

  2026

• SEMINAR (ADVANCED MOLECULAR CHEMISTRY)

  2026

• STUDY OF MAJOR FIELD (ADVANCED MOLECULAR CHEMISTRY)

  2026

• BACHELOR'S THESIS

  2026

• DRUG DISCOVERY SCIENCES

  2026

display all >>