奈良先端科学技術大学院大学 物質創成科学領域

Division of Materials Science NARA Institute of Science and Technology

Functional Supramolecular Chemistry Laboratory

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. Based on the chemical knowledge of the functions and structures of biomolecules at molecular level, our laboratory focuses on the elucidation of protein mechanisms and design/application of bio-supramolecules using various analytical 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. Relationship between disease and protein denaturation mechanism

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. We also study the aggregation process of antibodies.

4. 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.

5. 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.

6.Computer-based protein design

We design functional proteins using deep learning and purify them by wet experiments.

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. M. Zhang et al., J. Phys. Chem. B, 127, 2442 (2023).
  2. S. Hirota et al., Chem. Commun., 58, 12839 (2022).
  3. S. T. Stripp et al., Chem. Rev., 122, 11900 (2022).
  4. H. Tai et al. , Acc. Chem. Res., 54, 232 (2021).
  5. S. Hirota, et al. Chem. Commun., 57, 12074 (2021) (Future Article).
  6. S. Hirota, S. Nagao, Bull. Chem. Soc. Jpn., 94, 170 (2021) (Award Account, Inside Cover)
  7. C. Xie et al., RSC Advances, 11, 37604 (2021).
  8. M. Yamanaka et al., PLoS One, 16, e0259052 (2021).
  9. S. Nagao et al., J. Inorg. Biochem., 217, 111374 (2021).
  10. S. Nagao et al., Chem. Asian J., 15, 1743 (2020) (Very Important Paper).
  11. H. Tai, S. Hirota, ChemBioChem, 21, 1573 (2020) (Very Important Paper).
  12. T. Miyake, T. Matsuo et al., Bioconjugate Chem., 31, 794 (2020).
  13. R. Cahyono et al., Metallomics, 12, 337 (2020) (Front Cover)