Exploring novel innate immune stimulants ; Structure elucidation, chemical synthesis and functions of bacterial surface components

2009 Fiscal Year Final Research Report

• Project/Area Number: 19310144
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: Osaka University
• Principal Investigator: FUJIMOTO Yukari Osaka University, 大学院・理学研究科, 准教授 (00362616)
• Project Period (FY): 2007 – 2009
• Keywords: 自然免疫 / 複合糖質 / 有機合成化学 / ペプチドグリカン / Nod1

Research Abstract

In order to understand the molecular structures and bioactivities of innate immune stimulators in the environment, we isolated and elucidated the structures of natural innate immune receptor (eg. Nod1)'s ligands, and also succeeded the chemical synthesis of bacterial cell wall peptidoglycan fragments (including tracheal cytotoxin (TCT)), and a phsphoglycolipid from an extreme thermophile, for the first time.

Research Products

• [Journal Article] Characterization of natural human nucleotide-binding oligomerization domain protein 1 (NOD1) ligands from bacterial culture supernatant for elucidation of immune modulators in the environment. (2010)
  • Author(s): Pradipta, A.R., Fujimoto, Y., Hasegawa, M., Inohara, N., Fukase, K.
  • Journal Title: J.Biol.Chem. 285 Pages: 23607-23613
  • Peer Reviewed
• [Journal Article] Widely applicable deprotection method of 2,2,2-trichloroethoxycarbonyl (Troc) group using tetrabutylammonium fluoride. (2010)
  • Author(s): Huang, C-y., Wang, N., Fujiki, K., Otsuka, Y., Akamatsu, M., Fujimoto, Y., Fukase, K.
  • Journal Title: J.Carbohydr.Chem. 29 Pages: 1-9
  • Peer Reviewed
• [Journal Article] The peptide sequence of diacyl lipopeptides determines dendritic cell TLR2-mediated NK activation. (2010)
  • Author(s): Azuma, M., Sawahata R., Akao, Y., Ebihara, T., Yamazaki, S., Matsumoto, M., Hashimoto, M., Fukase, K., Fujimoto, Y., Seya, T.
  • Journal Title: PLos One 5 Pages: e12550
  • Peer Reviewed
• [Journal Article] Nucleotide oligomerization binding domain-like receptor signaling enhances dendritic cell-mediated cross-priming in vivo. (2010)
  • Author(s): Asano, J., Tada, H., Onai, N., Sato, T., Horie, Y., Fujimoto, Y., Fukase, K., Suzuki, A., Mak, T.W., Ohteki, T.
  • Journal Title: J.Immunol. 184 Pages: 736-745
  • Peer Reviewed
• [Journal Article] Structural prerequisites for endotoxic activity in the Limulus test as compared to cytokine production in mononuclear cells. (2010)
  • Author(s): Gutsmann, T., Howe, J., Zahringer, U., Garidel, P., Schromm, A.B., Koch, M.H., Fujimoto, Y., Fukase, K., Moriyon, I., Martinez-de-Tejada, G., Brandenburg, K.
  • Journal Title: Innate Immun. 16 Pages: 39-47
  • Peer Reviewed
• [Journal Article] Multimeric bivalent immunogens from recombinant tetanus toxin HC fragment, synthetic hexasaccharides, and a glycopeptide adjuvant. (2010)
  • Author(s): Bongat, A.F.G., Saksena, R., Adamo, R., Fujimoto, Y., Shiokawa, Z., Peterson, D. C., Fukase, K., Vann, W.F., Kova., P.
  • Journal Title: Glycoconj.J. 27 Pages: 69-77
  • Peer Reviewed
• [Journal Article] Lipopeptides from Staphylococcus aureus as Tlr2 Ligands: Prediction with mRNA Expression, Chemical Synthesis, and Immunostimulatory Activities. (2009)
  • Author(s): Fujimoto, Y., Hashimoto, M., Furuyashiki, M., Katsumoto, M., Seya, T., Suda, Y., Fukase, K.
  • Journal Title: ChemBioChem 10 Pages: 2273-2403
  • Peer Reviewed
• [Journal Article] Synthesis of crosslinked peptidoglycan fragments for investigation of their immunobiological functions. (2009)
  • Author(s): Fujimoto, Y., Konishi, Y., Kubo, O., Hasegawa, M., Inohara, N., Fukase. K.
  • Journal Title: Tetrahedron Lett. 50 Pages: 3631-3634
  • Peer Reviewed
• [Journal Article] Characterization of N-terminal Structure of TLR2-activating Lipoprotein in Staphylococcus aureus. (2009)
  • Author(s): Tawaratsumida, K., Furuyashiki, M., Katsumoto, M., Fujimoto, Y., Fukase, K., Suda Y., Hashimoto, M.
  • Journal Title: J.Biol.Chem. 284 Pages: 9147-9152
  • Peer Reviewed
• [Journal Article] Synthesis of diaminopimelic acid-containing peptidoglycan fragments and tracheal cytotoxin (TCT) for investigation of their biological functions. (2008)
  • Author(s): Kawasaki, A., Karasudani, Y., Otsuka, Y., Hasegawa, M., Inohara, N., Fujimoto, Y., Fukase, K.
  • Journal Title: Chem.Eur.J. 14 Pages: 10318-10330
  • Peer Reviewed
• [Journal Article] Autophagic control of listeria through intracellular innate immune recognition in drosophila. (2008)
  • Author(s): Yano, T., Mita, S., Ohmori, H., Oshima, Y., Fujimoto, Y., Ueda, R., Takada, H., Goldman, W.E., Fukase, K., Silverman, N., Yoshimori, T., Kurata, S.
  • Journal Title: Nat.Immunol. 9 Pages: 908-916
  • Peer Reviewed
• [Journal Article] Synthesis of Rubrivivax gelatinosus lipid A and analogues for investigation of the structural basis for immunostimulating and inhibitory activities. (2008)
  • Author(s): Fukase, Y., Fujimoto, Y., Adachi, Y., Suda, Y., Kusumoto, S., Fukase, K.
  • Journal Title: Bull.Chem.Soc.Japan. 81(Award Article) Pages: 796-819
  • Peer Reviewed
• [Journal Article] A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation. (2008)
  • Author(s): Hasegawa, M., Fujimoto, Y., Lucas, P.C., Nakano, H., Fukase, K., Nunez, G., Inohara, N.
  • Journal Title: EMBO J. 27 Pages: 373-383
  • Peer Reviewed
• [Journal Article] Molecular cloning and functional characterization of porcine nucleotide-binding oligomerization domain-1 (NOD1) recognizing minimum agonists, meso-diaminopimelic acid and meso-lanthionine. (2008)
  • Author(s): Tohno, M., Shimazu, T., Aso, H., Uehara, A., Takada, H., Kawasaki, A., Fujimoto, Y., Fukase, K., Saito, T., Kitazawa, H.
  • Journal Title: Mol.Immunol. 45 Pages: 1807-1817
  • Peer Reviewed
• [Journal Article] Differential Activation of Human TLR4 by Escherichia coli and Shigella flexneri 2a Lipopolysaccharide : Combined Effects of Lipid A Acylation State and TLR4 Polymorphisms on Signaling. (2008)
  • Author(s): Rallabhandi, P., Awomoyi, A., Thomas, K.E., Phalipon, A., Fujimoto, Y., Fukase, K., Kusumoto, S., Qureshi, N., Sztein, M.B., Vogel, S.N.
  • Journal Title: J.Immunol. 180 Pages: 1139-1147
  • Peer Reviewed
• [Journal Article] Synthesis of immunoregulatory Helicobacter pylori lipopolysaccharide partial structures. (2007)
  • Author(s): Fujimoto, Y., Iwata, M., Imakita, N., Shimoyama, A., Suda, Y., Kusumoto, S., Fukase, K.
  • Journal Title: Tetrahedron Lett. 48 Pages: 6577-6581
  • Peer Reviewed
• [Journal Article] Chemical synthesis of peptidoglycan fragments for elucidation of the immunostimulating mechanism. (2007)
  • Author(s): Fujimoto, Y., Inamura, S., Kawasaki, A., Shiokawa, Z., Shimoyama, A., Hashimoto, T., Kusumoto, S., Fukase, K.
  • Journal Title: J.Endotoxin Research 13 Pages: 189-196
  • Peer Reviewed
• [Journal Article] Synthesis and functional analysis of the key compounds responsible for signal transduction. (2007)
  • Author(s): Fujimoto, Y.
  • Journal Title: Yuki Gosei Kagaku Kyokaishi 65 Pages: 1170-1178
  • Peer Reviewed
• [Journal Article] Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines. (2007)
  • Author(s): Uehara, A., Fujimoto, Y., Fukase, K., Takada, H.
  • Journal Title: Mol.Immunol. 44 Pages: 3100-3111
  • Peer Reviewed
• [Journal Article] Nod1/RICK and TLR signaling regulate chemokine and antimicrobial innate immune responses in mesothelial cells. (2007)
  • Author(s): Park, J.H., Kim, Y.G., Shaw, M., Kanneganti, T.D., Fujimoto, Y., Fukase, K., Inohara, N., Nunez, G.
  • Journal Title: J.Immunol. 179 Pages: 514-521
  • Peer Reviewed
• [Journal Article] Evidence of immunostimulating lipoprotein existing in the natural lipoteichoic acid fraction. (2007)
  • Author(s): Hashimoto, M., Furuyashiki, M., Kaseya, R., Fukada, Y., Akimaru, M., Aoyama, K., Okuno, T., Tamura, T., Kirikae, T., Kirikae, F., Eiraku, N., Morioka, H., Fujimoto, Y., Fukase, K., Takashige, K., Moriya, Y., Kusumoto, S., Suda, Y.
  • Journal Title: Infect.Immun. 75 Pages: 1926-1932
  • Peer Reviewed
• [Journal Article] Inhibition of lipid A-mediated type I interferon induction by bactericidal/permeability-increasing protein (BPI). (2007)
  • Author(s): Azuma, M., Matsuo, A., Fujimoto, Y., Fukase, K., Hazeki, K., Hazeki, O., Matsumoto, M., Seya, T.
  • Journal Title: Biochem.Biophys.Res.Commun. 354 Pages: 574-578
  • Peer Reviewed
• [Journal Article] A role of lipophilic peptidoglycan-related molecules in induction of Nod1-mediated immune responses. (2007)
  • Author(s): Hasegawa, M., Kawasaki, A., Yang, K., Fujimoto, Y., Masumoto, J., Breukink, E., Nunez, G., Fukase, K., Inohara, N.
  • Journal Title: J.Biol.Chem. 282 Pages: 11757-11764
  • Peer Reviewed
• [Presentation] Molecular Basis of Endotoxic Activities Based on Synthesized Various Lipid A/LPS Partial Structures. (2010)
  • Author(s): 藤本ゆかり
  • Organizer: 2010 Joint Meeting between the Society for Leukocyte Biology & the International Endotoxin and Innate Immunity Society.
  • Place of Presentation: (Vancourver, Canada
  • Year and Date: 20101007-20101009
• [Presentation] 自然免疫を活性化する細菌細胞壁ペプチドグリカン・フラグメントの構造解析,合成と機能 (2009)
  • Author(s): 藤本ゆかり
  • Organizer: 第51回天然有機化合物討論会
  • Place of Presentation: 名古屋市公会堂,愛知県
  • Year and Date: 20091007-20091009
• [Presentation] Synthesis and Biofunction of Innate Immunostimulating Glycoconjugates from Bacteria (2009)
  • Author(s): 藤本ゆかり
  • Organizer: Combinatorial Chemistry and Chemical Biology toward A New Paradigm for Drug Discovery (CCCB)
  • Place of Presentation: Senri Life Science Center, Osaka
  • Year and Date: 20090924-20090925
• [Presentation] Synthesis and Biofunction of Nod1 Ligands of Peptidoglycan ; Innate Immunostimulating Glycoconjugates from Bacteria (2009)
  • Author(s): 藤本ゆかり
  • Organizer: 15th European Carbohydrate Symposium (Eurocarb2009)
  • Place of Presentation: Viena, Austria
  • Year and Date: 20090719-20090724
• [Presentation] 細胞内自然免疫受容体Nod1に対するリガンドの合成と免疫増強作用 (2009)
  • Author(s): 藤本ゆかり
  • Organizer: 日本化学会第89春季年会
  • Place of Presentation: 日本大学,千葉
  • Year and Date: 20090327-20090330
• [Presentation] 自然免疫を活性化するバクテリア由来複合糖質の合成と機能 (2008)
  • Author(s): 藤本ゆかり
  • Organizer: 第6回糖質科学コンソーシアム(JCGG)シンポジウム
  • Place of Presentation: 東京コンファレンスセンター,東京
  • Year and Date: 20081203-20081204
• [Presentation] Synthetic study of bacterial glycoconjugates for understanding the molecular basis of innate immune system. (2008)
  • Author(s): 藤本ゆかり
  • Organizer: The 22nd Naito Conference on Chemical Biology.
  • Place of Presentation: The Chateraise Gateaux Kingdom SAPPORO, Sapporo
  • Year and Date: 20080909-20080912
• [Presentation] Synthesis of diaminopimelic acidcontaining peptidoglycan fragmentsand tracheal cytotoxin (TCT) forinvestigation of their biologicalfunctions (2008)
  • Author(s): 藤本ゆかり
  • Organizer: 10th Biennial Meeting of the International Endotoxin and Innate Immunity Society (IEIIS2008)
  • Place of Presentation: Edinburgh, UK
  • Year and Date: 20080730-20080802
• [Presentation] Synthesis of immunostimulatorypeptidoglycan fragments recognized bythe intracellular receptors (2008)
  • Author(s): 藤本ゆかり
  • Organizer: The International Conference on Biodiversity and Natural Products ((IUPAC) ICOB-6 and ISCNP-26)
  • Place of Presentation: Charlottetown, Canada
  • Year and Date: 20080713-20080718
• [Presentation] Synthetic study of bacterial glycoconjugates for understanding the molecular basis of innate immune system (2008)
  • Author(s): 藤本ゆかり
  • Organizer: The 10th International Symposium on Biotechnology, Metal Complexes and Catalysis (BMC-X)
  • Place of Presentation: Zhengzhou, China
  • Year and Date: 20080512-20080515
• [Presentation] 高度好熱菌Thermus thermophilus糖脂質の全合成と免疫刺激活性 (2007)
  • Author(s): 藤本ゆかり
  • Organizer: 第49回天然有機化合物討論会
  • Place of Presentation: 札幌コンベンションセンター,北海道
  • Year and Date: 20070919-20070921
• [Presentation] 生体内の情報伝達に関わる鍵化合物の合成と機能解析 (2007)
  • Author(s): 藤本ゆかり
  • Organizer: 第24回有機合成化学セミナー
  • Place of Presentation: 淡路夢舞台国際会議場,兵庫
  • Year and Date: 20070912-20070914
• [Presentation] Synthesis of immunostimulating peptidoglycan fragments recognized by intracellular receptor (2007)
  • Author(s): 藤本ゆかり
  • Organizer: The 216th American Chemical Society (ACS) National Meeting
  • Place of Presentation: Boston, USA
  • Year and Date: 20070823-20070827
• [Book] Methods in Enzymology ; Self and non-self recognition with bacterial and animal glycans, surveys by synthetic chemistry.(Minoru Fukuda Ed.) (2010)
  • Author(s): Fujimoto, Y., Tanaka, K., Shimoyama, A., Fukase, K.
  • Total Pages: 323-334
  • Publisher: Elsevier
• [Book] Chemical synthesis of bacterial lipid A. In Microbial Glycobiology : Structures, Relevance and Applications, Anthon Moran, Otto Holst, Patrick J Brennan,(Mark von Itzstein Eds.)London (2009)
  • Author(s): Kusumoto, S., Fukase, K., Fujimoto, Y.
  • Total Pages: 415-427
  • Publisher: Elsevier
• [Book] Synthesis and biofunctional studies of bacterial immunostimulating glycoconjugates. In Progress in the synthesis of complex carbohydrate chains of plant and microbial polysaccharides.(Nikolay E. Nifantiev Ed.) (2009)
  • Author(s): Fukase, K., Fujimoto, Y.
  • Total Pages: 279-308
  • Publisher: Research Signpost and Transworld Research Network
• [Book] Chemical Synthesis of Sugar Chains In Experimental Glycoscience, "Glycochemistry"(Taniguchi, N., Suzuki, A., Ito, Y., Narimatsu, H., Kawasaki, T., Hase, S. Eds.)London (2008)
  • Author(s): Fukase, K., Fujimoto, Y., Tanaka, K.
  • Total Pages: 200-205
  • Publisher: Springer-Verlag
• [Book] Combinatorial methods on oligosaccharide synthesis. In Glycoscience, 2nd ed. Chemistry and Chemical Biology(Fraser-Reid, B.O., Tatsuta, K., Thiem, J., Cote, G.L., Flitsch, S., Ito, Y., Kondo, H., Nishimura, S.-i., Yu, B., Eds.)Berlin (2008)
  • Author(s): Tanaka, K., Fujimoto, Y., Tanaka, S., Mori, Y., Fukase, K.
  • Total Pages: 1205-1240
  • Publisher: Springer-Verlag
• [Book] Synthesis of Lipopolysaccharide, Peptidoglycan and Lipoteichoic Acid Fragments. In Comprehensive Glycoscience: From Chemistry to Systems Biology(Kamerling, J. P., Boons, G-J., Lee, Y. C., Suzuki, A., Taniguchi, N., Eds.)London (2007)
  • Author(s): Kusumoto, S., Fukase, K., Fujimoto, Y.
  • Total Pages: 685-711
  • Publisher: Elsevier
• [Book] Meso-diaminopimelic acid and meso-lanthionine, amino acids peculiar to bacterial cell wall peptidoglycans, activate human epithelial cells in culture via NOD1. In Interface Oral Health Science 2007(Watanabe, M., Okuno, O., Eds.)Tokyo (2007)
  • Author(s): Uehara, A., Fujimoto, Y., Kawasaki, A., Fukase, K., Takada, H.
  • Total Pages: 275-276
  • Publisher: Springer
• [Book] Expression of various Toll-like receptors, NOD1, and NOD2, in human oral epithelial cells, and their function. In Interface Oral Health Science 2007(Watanabe, M., Okuno, O., Eds.)Tokyo (2007)
  • Author(s): Sugawara, Y., Uehara, A., Fujimoto, Y., Kawasaki, A., Fukase, K., Sasano, T., Takada, H.
  • Total Pages: 225-230
  • Publisher: Springer