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Functional Supramolecular Chemistry

Staff & Contact

Educational Staff Prof. Shun Hirota
Associate Prof. Takashi Matsuo
Assistant Prof.Naoya Kobayashi, Tsuyoshi Mashima
Contact TEL: +81-743-72-6110
URL https://mswebs.naist.jp/LABs/hirota/index_e.html

Education and Research Activities in the Laboratory

We are performing new interdisciplinary researches in chemistry and biology. In living organisms, a variety of biomolecules such as proteins, DNA, and sugars form unique supramolecular assemblies to maintain biofunctions. Based on chemical knowledge of the functions and structures of these bio-supramolecules at the molecular level, our laboratory focuses on elucidation of the function mechanisms and design/applications of bio-supramolecules using various spectroscopic analysis methods, protein engineering techniques, and organic syntheses.

Research Themes

1. New protein drug development

We make new protein drugs from human antibody light chains. We also design and make artificial proteins with multi-active sites exhibiting antibacterial activity (Fig. 1). These protein drugs are attracting attention in the biotechnology and pharmaceutical science fields.

2. Bio-supramolecule creation

It would be extremely useful for life if we could create new proteins as we like. For this purpose, we construct new protein supramolecules by introducing a new design method in which building block proteins are used as structural units (Fig. 2).

3. Elucidation of protein denaturalization processes at the molecular level

Accumulation of proteins with unusual structures in tissues causes various diseases such as abnormal hemoglobin disease, Alzheimer's disease, and Parkinson's disease (conformational diseases). We investigate denaturalization of these proteins at the molecular level and develop strategies to inhibit the denaturalization.

4. Reaction mechanism elucidation of metalloenzymes

To understand the chemistry of life, we investigate enzymatic reactions using spectroscopic methods. For example, we elucidate the H2 production and decomposition mechanisms of a metalloenzyme, hydrogenase.

5. Functionalization of proteins by synthetic chemistry

We develop novel biocatalysts and artificial proteins using synthetic chemistry and biochemical approaches. The functionalized proteins will be applied for organic syntheses and regulation of naturally occurring bioreactions (Fig. 3). In this view, we synthesize novel synthetic compounds that are hybridized with biomolecules.

6.Functional analysis of interaction fashions between biomolecules for medicinal chemistry

To understand and regulate bioreactions, we develop methods for bioreaction regulation based on interactions between biomolecules from the perspective of medicinal chemistry and chemical biology.

Explanatory Pictures of Research Activities

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Fig. 1 Creation of antibacterial protein supramolecules
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Fig. 2 Elucidated structures of cytochrome c supramolecules
Fig. 3 X-ray crystallographic structure of an artificial fluorescent protein constructed by a combination of genetic and synthetic methods

Recent Research Papers and Achievements

1.S. Nagao et al., Chem. Asian J., 15, 1743 (2020) (Very Important Paper).  
2. H. Tai, S. Hirota, ChemBioChem, 21, 1573 (2020) (Very Important Paper).  
3. T. Miyake, T. Matsuo et al., Bioconjugate Chem., 31, 794 (2020).  
4. R. Cahyono et al., Metallomics, 12, 337 (2020) (Front Cover).  
5. P. P. Parui et al., Chem. Sci., 10, 9140 (2019).  
6. T. Matsuo et al., Tetrahedron Lett., 60, 151226 (2019) (Front Cover).  
7. H. Tai et al., Angew. Chem. Int. Ed., 58, 13285 (2019).  
8. T. Miyamoto et al., ACS Synth. Biol., 8, 1112 (2019).  
9. A. Oda et al., Chem. Asian J., 13, 964 (2018) (Front Cover).
10. T. Matsuo et al., Chem. Eur. J., 24, 2767 (2018).
11. Y. Shomura et al., Science, 357, 928 (2017).
12. K. Yuyama et al., Angew. Chem. Int. Ed., 56, 6739 (2017) (Hot Paper)