Department of Applied Molecular Biosciences

Division of Biofunctional Chemistry

LAB. OF ORGANIC CHEMISTRY

  FAX: +81-52-789-4111
Prof. NISHIKAWA, Toshio D. Agr. nisikawa@
Assoc. Prof. NAKAZAKI, Atsuo D. Eng. nakazaki@
Lecturer ADACHI, Masaatsu D. Eng. madachi@
Photo3-2-1

This research group deals with the graduate and undergraduate education and research program for basic organic chemistry, synthetic chemistry, bioorganic chemistry and chemical biology centered on natural products.

These include the following subjects;

  1. Total syntheses of biologically active compounds.
  2. Development of new synthetic methodologies.
  3. Elucidation and analysis of the biological functions of natural products at the molecular level.
  4. Molecular design of new biologically active molecules on the basis of natural products.

Recent Publications:

  1. Adachi, M.; Imazu, T.; Sakakibara, R.; Satake, Y.; Isobe, M.; Nishikawa, T. Total Synthesis of Chiriquitoxin, an Analog of Tetrodotoxin Isolated from the Skin of a Dart Frog, Chem. Eur. J. 2014, 20, 1247-1251. 
  2. Nakazaki, A.; Ishikawa, Y.; Sawayama, Y.; Yotsu-Yamashita, M.; Nishikawa, T. Synthesis of Crambescin B Carboxylic Acid, a Potent Inhibitor of Voltage-gated Sodium Channels, Org. Biomol. Chem. 2014, 12, 53–56. 
  3. Yamada, H.; Adachi, M.; Isobe, M.; Nishikawa, T. Stereocontrolled Synthesis of the Oxathiabicyclo[3.3.1]nonane Core Structure of Tagetitoxin, Chem. Commun. 2013, 49, 11221-11223. 
  4. Sawayama, Y.; Nishikawa, T. A Synthetic Route of the Saxitoxin Skeleton: Synthesis of Decarbamoyl-a-saxitoxinol, an Analog of Saxitoxin Produced by the Cyanobacterium Lyngbya wollei,Angew. Chem. Int. Ed. 2011, 50, 7176-7178.

LAB. OF BIOACTIVE NATURAL PRODUCTS CHEMISTRY

  FAX: +81-52-789-4118
Prof. OJIKA, Makoto D. Sci. ojika@
Assoc. Prof. NAKAGAWA, Yu D. Agr. yu@
Lecturer KONDO, Tatsuhiko D. Agr. kontatsu@

The primary objective of studies in this laboratory is to investigate the bioactive natural products, which will be potentially useful for agricultural or medical application. Research in this laboratory principally concerns the isolation and structure elucidation of the natural products and their receptors, which play an important role in controlling the life cycle of plants, microorganisms and other living organisms. The biosynthesis and action mechanism of the discovered compounds are also belonging to our main research projects. The natural products or their synthetic analogues provide clues for building up new types of bio-regulators. The following subjects are in progress:

  1. Chemical biological studies on microbial hormones, antibiotics, and other pharmaceutical leads.
  2. Mechanistic studies and therapeutic applications of carbohydrate-binding natural products.
  3. Bioorganic studies on plant hormones and mediators of plant-microbe interactions.

Recent publications:

  1. Han, C.; Furukawa, H.; Tomura, T.; Fudou, R.; Kaida, K.; Choi, B.-K.; Imokawa, G.; Ojika, M. Bioactive Maleic Anhydrides and Related Diacids from the Aquatic Hyphomycete Tricladium castaneicola, J. Nat. Prod. 2015, 78, 639-644.
  2. Makoto Ojika, Shylaja D. Molli, Harumi Kanazawa, Arata Yajima, Kou Toda, Tomoo Nukada, Haimeng Mao, Ryo Murata, Tomoyo Asano, Jianhua Qi & Youji Sakagami, The second Phytophthora mating hormone defines interspecies biosynthetic crosstalk, Nat. Chem. Biol. 2011, 7, 591-593.
  3. Nakagawa, Y.; Doi, T.; Masuda, Y.; Takegoshi, K.; Igarashi, Y.; Ito, Y. Mapping of the Primary Mannose-Binding Site of Pradimicin A, J. Am. Chem. Soc., 2011, 14, 17485-17493.
  4. Nakagawa, Y.; Masuda, Y.; Yamada, K.; Doi, T.; Takegoshi, K.; Igarashi, Y.; Ito, Y. Solid-state NMR Spectroscopic Analysis of the Ca2+-dependent Mannose Binding of Pradimicin A, Angew. Chem. Int. Ed., 2011, 50, 6084-6088.
  5. Kondo, T.; Kajita, R.; Miyazaki, A.; Hokoyama, M.; Nakamura-Miura, M.; Mizuno, S.; Masuda, Y.; Irie, K.; Tanaka. Y.; Takada, S.; Kakimoto, T.; Sakagami, Y. Stomatal density is controlled by a mesophyll-derived signaling molecule, Plant Cell Physiol., 2010, 51, 1-8.
  6. Kondo, T.; Sawa, S.; Kinoshita, A.; Mizuno, S.T; Kakimoto, T.; Fukuda, F.; Sakagami, Y. A plant peptide encoded by CLV3 identified by in situ MALDI-TOF MS analysis, Science, 2006, 313, 845-848.

LAB. OF FOOD AND BIODYNAMICS

Assoc. Prof. SHIBATA, Takahiro D. Agr. shibatat@
 

The principal research objectives of this lab are to understand the relevance of a variety of small molecules as ligands and triggers of chemical reactions related to our health and diseases, particularly regarding chemicals generated within our bodies and/or encountered in the environment. We are studying these foundational areas using a variety of approaches including organic chemistry, biochemistry, and chemical biology.

The following studies are currently in progress:

  1. Covalent modification of proteins by endogenous molecules including lipid peroxidation-derived compounds.
  2. Biological significance of protein modification as triggers of innate immunity and inflammatory responses.
  3. Molecular basis of health benefits of functional food components including phytochemicals.
Cellular responses mediated by oxidized fatty acids and functional food components.

Recent publications:

  1. Miyashita, H., Chikazawa, M., Otaki, N., Hioki, Y., Shimozu, Y., Nakashima, F., Shibata, T., Hagihara, Y., Maruyama, S., Matsumi, N., and Uchida, K. (2014) Lysine pyrrolation is a naturally-occurring covalent modification involved in the production of DNA mimic proteins. Sci. Rep. 4, 5343.
  2. Shibata, T., Nakashima, F., Honda, K., Lu, Y.J., Kondo, T., Ushida, Y., Aizawa, K., Suganuma, H., Oe, S., Tanaka, H., Takahashi, T., and Uchida, K. (2014) Toll-like receptors as a target of food-derived anti-inflammatory compounds. J. Biol. Chem. 289, 32757-32772.
  3. Chikazawa, M., Otaki, N., Shibata, T., Miyashita, H., Kawai, Y., Maruyama, S., Toyokuni, S., Kitaura, Y., Matsuda, T., and Uchida, K. (2013) Multispecificity of immunoglobulin M antibodies raised against advanced glycation end products: involvement of electronegative potential of antigens. J. Biol. Chem. 288, 13204-13214.
  4. Shibata, T., Shimozu, Y., Wakita, C., Shibata, N., Kobayashi, M., Machida, S., Kato, R., Itabe, H., Zhu, X., Sayre, L. M., and Uchida, K. (2011) Lipid peroxidation modification of protein generates Nepsilon-(4-oxononanoyl)lysine as a pro-inflammatory ligand.  J. Biol. Chem. 286, 19943-19957.
  5. Shimozu, Y., Hirano, K., Shibata, T., Shibata, N., and Uchida, K. (2011) 4-Hydroperoxy-2-nonenal is not just an intermediate, but a reactive molecule that covalently modifies proteins to generate unique intramolecular oxidation products. J. Biol. Chem. 286, 29313-29324.
  6. Shibata, T., Kimura, Y., Mukai, A., Mori, H., Ito, S., Asaka, Y., Oe, S., Tanaka, H., Takahashi, T., and Uchida, K. (2011) Transthiocarbamoylation of proteins by thiolated isothiocyanates. J. Biol. Chem. 286, 42150-42161.
  7. Ishino, K., Wakita, C., Shibata, T., Toyokuni, S., Machida, S., Matsuda, S., Matsuda, T., and Uchida, K. (2010) Lipid peroxidation generates a body odor component trans-2-nonenal covalently bound to protein in vivo. J. Biol. Chem. 285, 15302-15313.
  8. Yamaguchi, S., Aldini, G., Ito, S., Morishita, N., Shibata, T., Vistoli, G., Carini, M., and Uchida, K. (2010) Δ12-Prostaglandin J2 as a product and ligand of human serum albumin: Formation of an unusual covalent adduct at His146. J. Am. Chem. Soc. 132, 824-832.
  9. Wakita, C., Maeshima, T., Yamazaki, A., Shibata, T., Ito, S., Akagawa, M., Ojika, M., Yodoi, J., and Uchida, K. (2009) Stereochemical configuration of 4-hydroxy-2-nonenal-cysteine adducts and their stereoselective formation in a redox-regulated protein. J. Biol. Chem. 284, 28810-28822.
  10. Kanayama, M., Yamaguchi, S., Shibata, T., Shibata, N., Kobayashi, M., Nagai, R., Arai, H., Takahashi, K., and Uchida, K. (2007) Identification of a serum component that regulates cyclooxygenase-2 gene expression in cooperation with 4-hydroxy-2-nonenal. J. Biol. Chem. 282, 24166-24174.

LAB. OF POLYMER CHEMISTRY

  FAX: +81-52-789-4140
Prof. AOI, Keigo D. Eng. aoi@
Assoc. Prof NOMURA, Nobuyoshi D. Eng. nnomura@

Creation of functional biomaterials is the fundamental research theme in this laboratory. The functional biomaterials include specially polymers based on biomaterials, artificial materials with sophisticated biological functions, and environmentally friendly synthetic polymers. Current research fields are: (a) Synthesis of glycoconjugates, particularly globular glycomacromolecules and their biological functions based on molecular and cellular recognition. (b) Synthesis of bio-inspired functional materials. (c) Development of functional materials via chemical modification of natural polymers, particularly, chitin. (d) Synthesis of biodegradable and biofunctional polyesters, poly(ester carbonate)s and poly(ester urethane)s utilizing natural resources. (e) Development of new methodologies for precise polymer synthesis.

Recent Publications:

  1. Hasegawa, T., Kishida, H., Nomura, N. and Moriya, T. Synthesis of Crystalline Poly(lactic acid) from Glycerol By-product via Hydrothermal Reaction and Stereoselective Polymerization
    Chem. Lett., 44, 375 (2015).
  2. Nomura, N., Akita, A., Ishii, R. and Mizuno, M. Random Copolymerization of ε-Caprolactone with Lactide Using a Homosalen-Al Complex. J. Am. Chem. Soc., 132, 1750 (2010).
  3. Matsumi, N., Yoshioka, N. and Aoi, K. Synthesis of Boric Ester Type Ion-gels by Dehydrocoupling of Cellulose with Hydroboranes in Ionic Liquid. Solid State Ionics, 226, 37 (2012).
  4. Nomura, N., Komiyama, S., Kasugai, H. and Saba, M. An Efficient Protocol of Iridium-Catalyzed Allylic Substitution Reaction and its Application to Polymer Synthesis: Complementary Regio- and Stereoselective Allylation Polycondensation via Ir- and Pd-catalyses. J. Am. Chem. Soc., 130, 812 (2008).
  5. Nakamura, R., Aoi, K. and Okada, M. Controlled Synthesis of a Chitosan-Based Graft Copolymer Having Polysarcosine Side Chains Using the NCA Method with a Carboxylic Acid Additive. Macromolecular Rapid Communications, 27, 1725 (2006).
  6. Nakamura, R., Aoi, K. and Okada, M. Interactions of Enzymes and a Lectin with a Chitin-Based Graft Copolymer Having Polysarcosine Side Chains. Macromolecular Bioscience, 4, 610 (2004).
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