Biofunctional Synthetic Chemistry Laboratory

Although many efficient bond-forming reactions have been developed in the synthetic organic chemistry field, these are rarely applied to the labeling or the conjugation methods in the live cells or animals. We are synthetically exploring the overlooked and therefore unique reactivity of the imines, which are readily derived from the various amines in biosystem, hinted by the true bioactive structures of the biomacromolecules in vivo; the new reactivity of imines could then be used to challenge the multi-step synthesis of the biofunctional molecules in living animals. For examples, we are investigating the method called "synthetic surgery", which could directly generate the bioactive natural products for remedy at any time and at any regions inside the body, by executing the cascade organic transformations and/or by generating the reagents for the specific transformations in the serum or on the target organs. Alternatively, our concept termed as "in vivo templated synthesis" could make the target organs or the biomacromolecules in living animals by themselves to generate the "most suited molecules" for their diagnosis and/or functional regulation purposes.

Research Subjects

• Exploring Unrevealed Reactivity of Imines and Post-Translational Modification
• Establishment of Noninvasive Synthetic Surgery: Multi-step Synthesis in Living Animal
• Synthesis of Biofunctional Molecules by In Vivo Templated and Microfluidic Approach

Publications

1. K. Tanaka, K. Moriwaki, S. Yokoi, K. Koyama, E. Miyoshi, K. Fukase:
   "Whole-Body Imaging of Tumor Cells by Azaelectrocyclization: Visualization of Metastasis Dependence on Glycan Structure"
   Bioorg. Med. Chem., 21, 1074-1077 (2013)
2. K. Tanaka, E. R. O. Siwu, S. Hirosaki, T. Iwata, R. Matsumoto, Y. Kitagawa, A. R. Pradipta, M. Okumura, K. Fukase:
   "Efficient Synthesis of 2,6,9-Triazabicyclo[3.3.1]nonanes through Amine-Mediated Formal [4+4] Reaction of Unsaturated Imines"
   Tetrahedron Lett., 53, 5899-5902 (2012)
3. K. Tanaka, S. Shirotsuki, C. Kageyama, T. Tahara, S. Nozaki, E. R. O. Siwu, T. Iwata, S. Tamura, S. Douke, N. Murakami, H. Onoe, Y. Watanabe, K. Fukase:
   "Template-Assisted and Self-Activating Clicked Peptide as a Synthetic Mimic of the SH2 Domain"
   ACS Chem. Biol., 7, 637-645 (2012)
4. K.Tanaka, K. Fukase, S. Katsumura:
   "Exploring A Unique Reactivity of 6π-Azaelectrocyclization to Enzyme Inhibition, Natural Products Synthesis, and Molecular Imaging: An Approach to Chemical Biology by Synthetic Chemists"
   Synlett, 2115-2139 (2011)
5. K. Tanaka, M. Kitadani, K. Fukase:
   "Target-Selective and Fluorescence "Switch-On" Protein Labeling by 6π-Azaelectrocyclization"
   Org. Biomol. Chem., 9, 5346-5349 (2011)
6. K. Tanaka, E. R. O. Siwu, K. Minami, K. Hasegawa, S. Nozaki, Y. Kanayama, K. Koyama, C. W. Chen, J. C. Paulson, Y. Watanabe, K. Fukase:
   "Noninvasive Imaging of Dendrimer-type N-Glycan Clusters: In Vivo Dinamics Dependence on Oligosaccharides Structure"
   Angew. Chem. Int. Ed., 49, 8195-8200 (2010)
7. K. Tanaka, K. Minami, T. Tahara, E. R. O. Siwu, K. Koyama, S. Nozaki, H. Onoe, Y. Watanabe, K. Fukase:
   "A Combined 6π-Azaelectrocyclization/Staudinger Approach to Protein & Cell Engineering: Non-Invasive Tumor Targeting by N-Glycan-Engineered Lymphocytes"
   J. Carbohydr. Chem., 29, 118-132 (2010)
8. K. Tanaka, K. Minami, T. Tahara, Y. Fujii, E. R. O. Siwu, S. Nozaki, H. Onoe, S. Yokoi, K. Koyama, Y. Watanabe, K. Fukase:
   "Electrocyclization-Based Labeling Allows Efficient In Vivo Imaging of Cellular Trafficking"
   ChemMedChem, 5, 841-845 (2010)
9. K. Tanaka, K. Fukase:
   "Renaissance of Traditional Organic Reactions under Microfluidic Conditions: A New Paradigm for Natural Products Synthesis"
   Org. Process Res. Dev., 13, 983-990 (2009)
10. K. Tanaka, T. Masuyama, K. Hasegawa, T. Tahara, H. Mizuma, Y. Wada, Y. Watanabe, K. Fukase:
    "A Submicrogram-scale Protocol for Biomolecule-based PET Imaging via Rapid 6π -Azaelectrocyclization: First Visualization of Sialic Acid-dependent Circulatory Residence of Glycoproteins"
    Angew. Chem. Int. Ed., 47, 102-105 (2008)