金原研究室

研究内容

生物は複雑な機能性生体分子から成り立っており、有機化学が到達できる究極的な姿を示しています。私達はこのような生体分子の構造と機能に着目し、有機合成化学を武器として、これまでに無い機能を有する新物質の開発にチャレンジしています。

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1. 人工イオンチャネルの開発

親水性部位と疎水性部位を交互に連結した複数回膜貫通型分子を開発しました。この分子は、脂質二重層中で自己組織化し、生体内のイオンチャネルのような物質透過能・外部刺激応答性を示します。

Mechano-Sensitive Synthetic Ion Channels
Takahiro Muraoka, Kaori Umetsu, Kazuhito Tabata, Tsutomu Hamada, Hiroyuki Noji, Takashi Yamashita, and Kazushi Kinbara
J. Am. Chem. Soc2017, 139, 18016–18023 (10.1021/jacs.7b09515).

Reversible Ion Transportation Switch by a Ligand-Gated Synthetic Supramolecular Ion Channel
Takahiro Muraoka, Takahiro Endo, Kazuhito V. Tabata, Hiroyuki Noji, Satoru Nagatoishi, Kouhei Tsumoto, Rui Li and Kazushi Kinbara
J. Am. Chem. Soc. 2014, 136, 15584–15595.

Ion Permeation by a Folded Multiblock Amphiphilic Oligomer Achieved by Hierarchical Construction of Self-Assembled Nanopores
Takahiro Muraoka, Tatsuya Shima, Tsutomu Hamada, Masamune Morita, Masahiro Takagi, Kazuhito V. Tabata, Hiroyuki Noji, and Kazushi Kinbara
J. Am. Chem. Soc. 2012134, 19788–19794.

Mimicking Multipass Transmembrane Proteins: Synthesis, Assembly and Folding of Alternating Amphiphilic Multiblock Molecules in Liposomal Membranes
Takahiro Muraoka, Tatsuya Shima, Tsutomu Hamada, Masamune Morita, Masahiro Takagi, and Kazushi Kinbara
Chem. Commun. 201147, 194–196. [Selected as a Hot Article]

2. 構造化PEG分子の開発

多分散の生体適合性高分子である直鎖状ポリエチレングリコール(PEG)を、単分散・多角形型に構造化した分子を開発しました。構造化PEGは直鎖状PEGとは全く異なる物理的性質を示し、生体分子を安定化します。

Synthesis and Thermal Responses of Polygonal Poly(ethylene glycol) Analogues
Shunichi Kawasaki, Takahiro Muraoka, Tsutomu Hamada, Kazuki Shigyou, Fumi Nagatsugi and Kazushi Kinbara
Chem. Asian J. 2016, 11, 1028–1035.

Protein Stabilization by an Amphiphilic Short Monodisperse Oligo(ethylene glycol)
Nabanita Sadhukhan, Takahiro Muraoka, Mihoko Ui, Satoru Nagatoishi, Kouhei Tsumoto, and Kazushi Kinbara
Chem. Commun. 2015, 51, 8457–8460.

Thermodriven Micrometer-Scale Aqueous-Phase Separation of Amphiphilic Oligoethylene Glycol Analogues
Shunichi Kawasaki, Takahiro Muraoka, Haruki Obara, Takerou Ishii, Tsutomu Hamada and Kazushi Kinbara
Chem. Asian J. 2014, 9, 2778–2788 (Selected as the Back Cover).

Thermal-Aggregation Suppression of Proteins by a Structured PEG Analogue: Importance of Denaturation Temperature for Effective Aggregation Suppression
Takahiro Muraoka, Nabanita Sadhukhan, Mihoko Ui, Shunichi Kawasaki, Enrikko Hazemi, Kota Adachi, and Kazushi Kinbara
Biochem. Eng. J. 2014, 86C, 41–48.

A Structured Monodisperse PEG for the Effective Suppression of Protein Aggregation
Takahiro Muraoka, Kota Adachi, Mihoko Ui, Shunichi Kawasaki, Nabanita Sadhukhan, Haruki Obara, Hidehito Tochio, Masahiro Shirakawa, and Kazushi Kinbara
Angew. Chem., Int. Ed. 201352, 2430–2434. [Selected as a “Very Important Paper (VIP)” and a Back Cover]

3. 新規タンパク質化学修飾法の開拓

ビオチン構造を導入した新規タンパク質化学修飾試薬を開発しました。修飾部位はリパーゼによって認識され、非常に穏和な条件で迅速に切り出されるため、従来は困難であったタンパク質の機能化を実現できます。

Enzymatically cleavable traceless biotin tags for protein PEGylation and purification
Adam M. Wawro, Yusuke Aoki, Takahiro Muraoka, Kouhei Tsumoto and Kazushi Kinbara
Chem. Commun., 2018, 54, 1913–1916 (10.1039/C7CC05814D).

これら以外にも、多岐に渡る研究を展開しています。詳しくは発表論文をご覧ください。

過去の研究内容

4. 分子機械の開発

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Toward Long-Distance Mechanical Communication: Studies on a Ternary Complex Interconnected by a Bridging Rotary Module
Hiroyuki Kai, Shinji Nara, Kazushi Kinbara, and Takuzo Aida
J. Am. Chem. Soc. 2008, 130, 6725–6727.

Toward Autonomously Operating Molecular Machines Driven by Transition-Metal Catalyst
Kenichi Tanaka and Kazushi Kinbara
Mol. BioSyst. 2008, 4, 512–514. [Emerging Investigators Issue, Highlighted in Chemical Science.]

Chiral Ferrocenes as Novel Rotary Modules for Molecular Machines
Kazushi Kinbara, Takahiro Muraoka, and Takuzo Aida
Org. Biomol. Chem. 2008, 1871–1876. [Selected as “Emerging Area” and “Front Cover”; The Top 10 Downloaded Articles in May 2008.]

Reversible Operation of Chiral Molecular Scissors by Redox and UV Light
Takahiro Muraoka, Kazushi Kinbara, and Takuzo Aida
Chem. Commun. 2007, 1441–1443.

Crystallographic and Chiroptical Studies on Tetraarylferrocenes for Use as Chiral Rotary Modules for Molecular Machines
Takahiro Muraoka, Kazushi Kinbara, Atsushi Wakamiya, Shigehiro Yamaguchi, and Takuzo Aida
Chem.–Eur. J. 2007, 13, 1724–1730.

A Self-Locking Molecule Operative with a Photoresponsive Key
Takahiro Muraoka, Kazushi Kinbara, and Takuzo Aida
J. Am. Chem. Soc. 2006, 128, 11600–11605.

Mechanical Twisting of a Guest by a Photoresponsive Host
Takahiro Muraoka, Kazushi Kinbara, and Takuzo Aida
Nature 2006, 440, 512–515. [Highlighted in Angewandte Chemie, C&EN, Nanotechweb.org, Newscientist and Photonics.com.]

Toward Intelligent Molecular Machines: Directed Motions of Biological and Artificial Molecules and Assemblies
Kazushi Kinbara and Takuzo Aida
Chem. Rev. 2005, 105, 1377–1400.

Light-Driven Open-Close Motion of Chiral Molecular Scissors
Takahiro Muraoka, Kazushi Kinbara, Yuka Kobayashi, and Takuzo Aida
J. Am. Chem. Soc. 2003, 125, 5612–5613. [Highlighted in Newscientist.]

5. 有機合成的アプローチによるタンパク質に対する機能付加

A Tubular Biocontainer: Metal Ion–Induced 1D Assembly of a Molecularly Engineered Chaperonin
Shuvendu Biswas, Kazushi Kinbara, Nobuhiro Oya, Noriyuki Ishii, Hideki Taguchi, and Takuzo Aida
J. Am. Chem. Soc. 2009, 131, 7556–7557.

Semibiological Molecular Machine with an Impremented “AND” Logic Gate for Regulation of Protein Folding
Shinichi Muramatsu, Kazushi Kinbara, Hideki Taguchi, Noriyuki Ishii, and Takuzo Aida
J. Am. Chem. Soc. 2006, 128, 3764–3769.

Toward Intelligent Molecular Machines: Directed Motions of Biological and Artificial Molecules and Assemblies
Kazushi Kinbara and Takuzo Aida
Chem. Rev. 2005, 105, 1377–1400.

Chaperonin-Mediated Stabilization and ATP-Triggered Release of Semiconductor Nanoparticles
Daisuke Ishii, Kazushi Kinbara, Yasuhiro Ishida, Noriyuki Ishii, Mina Okochi, Masafumi Yohda, and Takuzo Aida
Nature 2003, 423, 628–632. [Highlighted in Nature, C&EN, TRNmag.com, and Nanotechweb.org.]