Chief Scientist Laboratories Biofunctional Synthetic Chemistry Laboratory

Chief Scientist: Katsunori Tanaka (Ph.D.)

Japanese Page

Research Summary

Although many efficient bond-forming reactions have been developed in the field of synthetic organic chemistry, their utility typically fails to translate in complex mixtures present in cellular or living biosystems. As such, only a handful of effective labeling or conjugation methods in biosystems are readily available. To address this issue, we are synthetically exploring the unique reactivity of conjugated imines for their potential in novel chemical reactions. The benefit of this approach is that since a large part of amine-containing biomacromolecules are biosynthesized through imine chemistry, imine-mediated chemical reactions will not face the same challenges that classical synthetic organic chemical reactions face within living systems. In parallel to this work, our studies have also shown that the unique reactivity of imines could be involved in pathways that regulate biologically important processes.

Besides usage in methods of labeling or conjugation, the novel reactivity of imines, in combination with other advanced metal-catalyzed transformations, could alternatively be used in the multi-step synthesis of biofunctional molecules within living biosystems. Through a concept we refer to as “Therapeutic In Vivo Synthetic Chemistry”, we aim to develop an adaptable system where a cascade of organic transformations can be directly executed at target regions within the body during predefined times to generate a bioactive molecule that elicits a localized biological effect. Towards this goal, we are analyzing, with the use of molecular imaging, the complex “pattern recognition” mechanisms of natural glycans in vivo and applying the glycan-based interactions to direct various linked biomolecules to desired organs and tissues.

Main Research Fields

Chemistry

Related Research Fields

Complex Systems
Biological Sciences
Biology
Medicine, Dentistry & Pharmacy
Biomolecular Chemistry
Chemical Biology
Biofunctional Chemistry

Keywords

Molecular Imaging
Theranostics
Bioactive Compound
Glycan
Therapeutic In Vivo Synthetic Chemistry

Selected Publications

1. K. Vong, T. Tahara, S. Urano, I. Nasibullin, K. Tsubokura, Y. Nakao, A. Kurbangalieva, H. Onoe, Y. Watanabe, K. Tanaka:
"Disrupting tumor onset and growth via selective cell tagging (SeCT) therapy"
Sci. Adv., 7, eabg4038 (2021).
2. A. R. Pradipta, P. Ahmadi, K. Terashima, K. Muguruma, M. Fujii, T. Ichino, S. Maeda, K. Tanaka:
"Targeted 1,3-dipolar cycloaddition with acrolein for cancer prodrug activation"
Chem. Sci., 12, 5438-5449 (2021).
3. T.-C. Chang, K. Vong, T. Yamamoto, K. Tanaka:
"Prodrug activation by gold artificial metalloenzyme-catalyzed synthesis of phenanthridinium derivatives via hydroamination"
Angew. Chem. Int. Ed., 60, 2-11 (2021).
4. K. Vong, S. Eda, Y. Kadota, I. Nasibullin, T. Wakatake, S. Yokoshima, K. Shirasu and K. Tanaka:
"An artificial metalloenzyme biosensor can detect ethylene gas in fruits and Arabidopsis leaves"
Nature Commun., 10, 5746 (2019).
5. S. Eda, I. Nasibullin, K. Vong, N. Kudo, M. Yoshida, A. Kurbangalieva and K. Tanaka:
"Biocompatibility and therapeutic potential of glycosylated albumin artificial metalloenzymes"
Nature Catal., 2, 780-792 (2019).
6. K. Fujiki, Y. Kanayama, S. Yano, N. Sato, T. Yokokita, P. Ahmadi, Y. Watanabe, H. Haba and K. Tanaka:
"211At-Labeled immunoconjugate via a one-pot three-component double click strategy: Practical access to α-emission cancer radiotherapeutics"
Chem. Sci., 10, 1936-1944 (2019).
7. T. Tanei, A. R. Pradipta, K. Morimoto, M. Fujii, M. Arata, A. Ito, M. Yoshida, E. Saigitbatalova, A. Kurbangalieva, J.-I. Ikeda, E. Morii, S. Noguchi and K. Tanaka:
"Cascade reaction in human live tissue allows clinically applicable diagnosis of breast cancer morphology"
Adv. Sci., 6, 1801479 (2019).
8. M. Taichi, S. Nomura, I. Nakase, R. Imamaki, Y. Kizuka, F. Ota, N. Dohmae, S. Kitazume, N. Taniguchi, and K. Tanaka:
"In-situ ligation of high- and low-affinity ligands to cell surface receptors enables highly selective recognition"
Adv. Sci., 1700147 (2017).
9. K. Tsubokura, K. K. H. Vong, A. R. Pradipta, A. Ogura, S. Urano, T. Tahara, S. Nozaki, H. Onoe, Y. Nakao, R. Sibgatullina, A. Kurbangalieva, Y. Watanabe and K. Tanaka:
"In vivo gold complex catalysis within live mice"
Angew. Chem. Int. Ed., 56, 3579-3584 (2017).
10. L. Latypova, R. Sibgatullina, A. Ogura, K. Fujiki, A. Khabibrakhmanova, T. Tahara, S. Nozaki, S. Urano, K, Tsubokura, H. Onoe, Y. Watanabe, A. Kurbangalieva and K. Tanaka:
"Sequential double “clicks" toward structurally well-defined heterogeneous N-glycoclusters: The importance of cluster heterogeneity on pattern recognition in vivo"
Adv. Sci., 4, 1600394 (2017).