Details of a Researcher - Sasaki, Daisuke

Sasaki, Daisuke

写真a

Affiliation: Faculty of Science and Technology, Department of Chemistry ( Yagami )

Position: Associate Professor (Non-tenured)

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Career 【 Display / hide 】

2012.04

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2016.12

Graduate School of Pharmaceutical Sciences, The University of Tokyo (ERATO Kanai Life Science Catalysis Project), Synthetic Organic Chemistry Laboratory, Project Researcher
2013.11

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2016.12

Graduate School of Pharmaceutical Sciences, The University of Tokyo (ERATO Kanai Life Science Catalysis Project), Synthetic Organic Chemistry Laboratory, Project Manager
2017.01

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2019.12

University of Liverpool, Molecular Biophysics Group, Department of Biochemistry, Institute of Integrative Biology, Research Associate
2019.12

-

2021.03

Tokyo Medical and Dental University, Cellular and Structural Physiology Laboratory, Advanced Research Institute, Project Assistant Professor
2021.04

-

2026.03

Wakayama Medical University, Medicinal Chemistry Laboratory, Division of Pharmacy, School of Pharmaceutical Sciences, Lecturer

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Academic Background 【 Display / hide 】

2000.04

-

2003.03

Taki High School, Aichi, Japan, General Course
2003.04

-

2007.03

Doshisha University, Faculty of Engineering, Department of Molecular Science and Technology
2007.04

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2009.03

Kyoto University, Graduate School of Science, Department of Chemistry (Master's Course)
2009.04

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2012.03

Kyoto University, Graduate School of Science, Department of Chemistry (Doctoral Course)

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Research Areas 【 Display / hide 】

Nanotechnology/Materials / Chemical biology (Protein chemical synthesis, Protein chemical transformation)
Life Science / Structural biochemistry (X-ray crystallography, Cryo-EM single particle analysis, Small-angle X-ray scattering)
Life Science / Pharmaceutical chemistry and drug development sciences (Structure-Based Drug Design (SBDD))

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Research Keywords 【 Display / hide 】

Amyloid
Neurodegenerative disease
Enzyme

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Papers 【 Display / hide 】

Semi-synthesis of TDP-43 reveals the effects of phosphorylation in N-terminal domain on self-association

Daisuke Sasaki, Mao Tenda, Youhei Sohma

Communications Chemistry (Springer Science and Business Media LLC) 8 125 2025.04

Lead author, Corresponding author, Accepted
- Access to Document (DOI)
Amyloid-reoriented enzyme catalysis

Taka Sawazaki, Fuma Murai, Kai Yamamoto, Daisuke Sasaki, Youhei Sohma

Nature Communications (Springer Science and Business Media LLC) 16 3164 2025.04

Accepted
- Access to Document (DOI)
Catalysis driven by an amyloid–substrate complex

Taka Sawazaki, Daisuke Sasaki, Youhei Sohma

Proceedings of the National Academy of Sciences (Proceedings of the National Academy of Sciences) 121 ( 19 ) e2314704121 2024.05

Accepted, ISSN 0027-8424

　View Summary

Amine modification through nucleophilic attack of the amine functionality is a very common chemical transformation. Under biorelevant conditions using acidic-to-neutral pH buffer, however, the nucleophilic reaction of alkyl amines (pKa ≈ 10) is not facile due to the generation of ammonium ions lacking nucleophilicity. Here, we disclose a unique molecular transformation system, c atalysis driven by a myloid– s ubstrate comp l ex (CASL), that promotes amine modifications in acidic buffer. Ammonium ions attached to molecules with amyloid-binding capability were activated through deprotonation due to the close proximity to the amyloid catalyst formed by Ac-Asn-Phe-Gly-Ala-Ile-Leu-NH <sub>2</sub> ( NL6 ), derived from islet amyloid polypeptide (IAPP). Under the CASL conditions, alkyl amines underwent various modifications, i.e., acylation, arylation, cyclization, and alkylation, in acidic buffer. Crystallographic analysis and chemical modification studies of the amyloid catalysts suggested that the carbonyl oxygen of the Phe–Gly amide bond of NL6 plays a key role in activating the substrate amine by forming a hydrogen bond. Using CASL, selective conversion of substrates possessing equivalently reactive amine functionalities was achieved in catalytic reactions using amyloids. CASL provides a unique method for applying nucleophilic conversion reactions of amines in diverse fields of chemistry and biology.
- Access to Document (DOI)
Single crystal spectroscopy and multiple structures from one crystal (MSOX) define catalysis in copper nitrite reductases

Samuel L. Rose, Seiki Baba, Hideo Okumura, Svetlana V. Antonyuk, Daisuke Sasaki, Tobias M. Hedison, Muralidharan Shanmugam, Derren J. Heyes, Nigel S. Scrutton, Takashi Kumasaka, Takehiko Tosha, Robert R. Eady, Masaki Yamamoto, S. Samar Hasnain

Proceedings of the National Academy of Sciences (Proceedings of the National Academy of Sciences) 119 ( 30 ) e2205664119 2022.07

Accepted, ISSN 0027-8424

　View Summary

Many enzymes utilize redox-coupled centers for performing catalysis where these centers are used to control and regulate the transfer of electrons required for catalysis, whose untimely delivery can lead to a state incapable of binding the substrate, i.e., a dead-end enzyme. Copper nitrite reductases (CuNiRs), which catalyze the reduction of nitrite to nitric oxide (NO), have proven to be a good model system for studying these complex processes including proton-coupled electron transfer (ET) and their orchestration for substrate binding/utilization. Recently, a two-domain CuNiR from a Rhizobia species ( Br<sup>2D</sup> NiR) has been discovered with a substantially lower enzymatic activity where the catalytic type-2 Cu (T2Cu) site is occupied by two water molecules requiring their displacement for the substrate nitrite to bind. Single crystal spectroscopy combined with MSOX (multiple structures from one crystal) for both the as-isolated and nitrite-soaked crystals clearly demonstrate that inter-Cu ET within the coupled T1Cu-T2Cu redox system is heavily gated. Laser-flash photolysis and optical spectroscopy showed rapid ET from photoexcited NADH to the T1Cu center but little or no inter-Cu ET in the absence of nitrite. Furthermore, incomplete reoxidation of the T1Cu site (∼20% electrons transferred) was observed in the presence of nitrite, consistent with a slow formation of NO species in the serial structures of the MSOX movie obtained from the nitrite-soaked crystal, which is likely to be responsible for the lower activity of this CuNiR. Our approach is of direct relevance for studying redox reactions in a wide range of biological systems including metalloproteins that make up at least 30% of all proteins.
- Access to Document (DOI)
Reverse protein engineering of a novel 4‐domain copper nitrite reductase reveals functional regulation by protein–protein interaction

Daisuke Sasaki, Tatiana F. Watanabe, Robert R. Eady, Richard C. Garratt, Svetlana V. Antonyuk, S. Samar Hasnain

The FEBS Journal (Wiley) 288 ( 1 ) 262 - 280 2021.01

Lead author, Accepted, ISSN 1742-464X
- Access to Document (DOI)

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Reviews, Commentaries, etc. 【 Display / hide 】

Chemical synthesis of TDP-43 reveals the effects of post-translational phosphorylation on self-association

Daisuke Sasaki, Mao Tenda, Youhei Sohma

Abstract book of AMED International Symposium "Proteostasis in Biology and Medicine" 2025.08

Lead author
Semi-synthesis of TDP-43 reveals the effects of phosphorylation in N-terminal domain on self-association

Daisuke Sasaki, Mao Tenda, Youhei Sohma

Abstract book of 2025 Joint Conference - Korean Society for Protein Science (KSPS) & Protein Science Society of Japan (PSSJ) 2025.06

Lead author
アミロイドの分子認識に基づく選択的変換反応

澤崎鷹, 村井颯馬, 山本快, 佐々木大輔, 相馬洋平

第22回ホストーゲスト・超分子化学シンポジウム（東京）要旨集 2025.06
TDP-43リン酸化体の化学合成による自己会合性の構造生物学的研究

佐々木大輔, 天田真緒, 相馬洋平

第25回日本蛋白質科学会年会（姫路）要旨集 2025.06

Lead author
TDP-43リン酸化翻訳後修飾体の化学合成による自己会合性解析

天田真緒, 佐々木大輔, 相馬洋平

日本薬学会第145年会（福岡）要旨集 2025.03

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Presentations 【 Display / hide 】

Semi-synthesis of TDP-43 reveals the effects of phosphorylation in N-terminal domain on self-association

Daisuke Sasaki, Mao Tenda, Youhei Sohma

The International Chemical Congress of Pacific Basin Societies 2025 (Pacifichem 2025) (Honolulu),

2025.12
,
Oral presentation (general)
化学合成が明らかにしたTDP-43の翻訳後リン酸化が自己会合性に与える影響

佐々木大輔, 天田真緒, 相馬洋平

日本ケミカルバイオロジー学会第19回年会（京都）,

2025.06
,
Oral presentation (general)
TDP-43のN末領域リン酸化が自己会合性に与える影響の構造学的解析

佐々木大輔, 天田真緒, 相馬洋平

日本薬学会第145年会（福岡）,

2025.03
,
Oral presentation (general)
Semi-synthesis of TDP-43 modified in N-terminal domain revealed effects of post-translational phosphorylation on self-association

Daisuke Sasaki, Mao Tenda, Youhei Sohma

The 61st Japanese Peptide Synposium (Nagoya),

2024.10
,
Oral presentation (general)
TDP-43の病原性構造基盤の解明に向けた翻訳後修飾体化学合成経路の構築

佐々木大輔, 澤崎鷹, 相馬洋平

日本薬学会第143年会（札幌）,

2023.03
,
Oral presentation (general)

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

Elucidation of structural basis for the pathogenicity of a post-translationally modified TDP-43, an ALS factor

2024.04

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2027.03

Japan Society for the Promotion of Science, KAKENHI, Daisuke Sasaki, Grant-in-Aid for Scientific Research (C), Principal investigator
Elucidation of structural basis for LLPS regulation based on homogeneous chemical synthesis of a post-translationally modified TDP-43

2022.04

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2023.03

Wakayama Medical University, Wakayama Medical Award for Young Researchers, Daisuke Sasaki, Principal investigator

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Intellectual Property Rights, etc. 【 Display / hide 】

インドール構造選択的架橋剤およびそれを用いた複合体

Date applied： PCT/JP2017/009315 2017.03

Date published： WO2017/154997 A1 2017.09

Patent
Aβペプチド酸化体

Date applied：特願2013-239622 2013.11

Date announced：特開2015-017082 2015.01

Date issued：特許第6324032号

Patent
環状ペプチド及びこれを含有する医薬

Date applied：特願2013-061722 2013.03

Date announced：特開2014-141445 2014.08

Date issued：特許第5804463号

Patent

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Other 【 Display / hide 】

技術移転に係わる目利き人材育成プログラム（主催：国立研究開発法人科学技術振興機構）

2015年

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コーディネート基礎コース修了
ティーチングアシスタント（京都大学博士後期課程）

2011年

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京都大学理学部講義補助
リサーチアシスタント（京都大学博士後期課程）

2011年

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京都大学理学部教育研究補助（京都大学グローバルCOEプログラム「物質科学の新基盤構築と次世代育成国際拠点」）
ティーチングアシスタント（京都大学博士後期課程）

2010年

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京都大学理学部講義補助
リサーチアシスタント（京都大学博士後期課程）

2010年

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京都大学理学部教育研究補助（京都大学グローバルCOEプログラム「物質科学の新基盤構築と次世代育成国際拠点」）

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Courses Taught 【 Display / hide 】

BACHELOR'S THESIS

2026
SEMINAR IN CHEMISTRY

2026

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Courses Previously Taught 【 Display / hide 】

Drug Discovery Target Evaluation

Graduate School of Medical and Pharmaceutical Sciences, Wakayama Medical University

2024.04

-

Present
Medicinal Chemistry II

Division of Pharmacy, School of Pharmaceutical Sciences, Wakayama Medical University

2023.04

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Present
Medicinal Chemistry I

Division of Pharmacy, School of Pharmaceutical Sciences, Wakayama Medical University

2022.10

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Present
Practice of Chemical Pharmacy

Division of Pharmacy, School of Pharmaceutical Sciences, Wakayama Medical University

2022.04

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Present
Basic Parmaceutical Practice I

Division of Pharmacy, School of Pharmaceutical Sciences, Wakayama Medical University

2021.04

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Present