Chemical synthesis of glycans and glycoconjugates for elucidation of their functions in immune and nerve system

2010 Fiscal Year Final Research Report

• Project/Area Number: 20241053
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: Osaka University
• Principal Investigator: FUKASE Koichi Osaka University, 大学院・理学研究科, 教授 (80192722)
• Co-Investigator(Kenkyū-buntansha): FUJIMOTO Yukari 大阪大学, 大学院・理学研究科, 准教授 (00362616) ; TANAKA Katsunori 大阪大学, 大学院・理学研究科, 助教 (00403098)
• Project Period (FY): 2008 – 2010
• Keywords: 糖鎖 / 自然免疫 / PETイメージング / グリコシル化 / 固相合成 / 免疫増強 / 複合糖質 / 糖タンパク質

Research Abstract

New synthetic methods have been developed for glycans and glycoconjugates and applied them to the synthesis of complex bioactive molecules for the elucidation of action mechanisms. In particular, immunostimulating or immunomodulating glycoconjugates from bacteria were synthesized for elucidation of the recognition with innate immune receptors. Synthetic ligands for the innate immune receptors were used for the immune regulation. Bio-imaging studies of glycans and glycoproteins were also studied for the dynamic and kinetic analysis of glycans to unveil the unknown function of glycans.

Research Products

• [Journal Article] Non-invasive imaging of dendrimer-type N-glycan clusters : in vivo dynamics dependence on oligosaccharide structure. (2010)
  • Author(s): Tanaka, K., Siwu, R.O.E., Minami, K., Hasegawa, K., Nozaki, S., Kanayama, Y., Koyama, K., Chen, C.W., Paulson, C.J., Watanabe, Y., Fukase, K.
  • Journal Title: Angew.Chem.Int.Ed. 49 Pages: 8195-8200
  • Peer Reviewed
• [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(31) Pages: 23607-23613
  • Peer Reviewed
• [Journal Article] A combined 6p-azaelectrocyclization/ staudinger approach to protein & cell engineering : non-invasive tumor targeting by N-Glycan-engineered lymphocytes. (2010)
  • Author(s): Tanaka, K., Minami, K., Tahara, T., Siwu, E.R.O., Koyama, K., Nozaki, S., Onoe, H., Watanabe, Y., Fukase, K.
  • Journal Title: J.Carbohydr.Chem. 29 Pages: 118-132
  • Peer Reviewed
• [Journal Article] Electrocyclization-based labeling allows efficient in Vivo imaging of cellular trafficking. (2010)
  • Author(s): Tanaka, K., Minami, K., Tahara, T., Fujii, Y., Siwu, E.R.O., Nozaki, S.; Onoe, H., Yokoi, S., Koyama, K., Watanabe, Y., Fukase, K.
  • Journal Title: Chem Med Chem (5) Pages: 841-845
  • Peer Reviewed
• [Journal Article] Key st std lipopolysaccharide triggering the innate immune system of higher animals : Chemical synthesis and functional studies. (2010)
  • Author(s): Kusumoto, S., Fukase, K., Shiba.
  • Journal Title: Proc.Jpn.Acad., Ser.B 86(4) Pages: 322-337
  • Peer Reviewed
• [Journal Article] Lipopeptides from Staphylococcus aureus as Tlr2 Ligands : Prediction with mRNA Expression. (2009)
  • Author(s): Fujimoto, Y., Hashimoto, M., Furuyashiki, M., Katsumoto, M., Seya, T., Suda, Y., Fukase, K.
  • Journal Title: ChemBioChem. 10(14) Pages: 2311-2315
  • Peer Reviewed
• [Journal Article] Chemical N-glycosylation by asparagine under integrated microfluidic/batch conditions. (2009)
  • Author(s): Tanaka, K., Miyagawa, T., Fukase, K.
  • Journal Title: Synlett 10 Pages: 1571-1574
  • 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] Synthesis of a sialic acid containing complex-type N-glycan on a solid support. (2009)
  • Author(s): Tanaka, K., Fujii, Y., Tokimoto, H., Mori, Y. Tanaka, S. Bao, G., Siwu, E.R.O., Nakayabu, A., Fukase, K.
  • Journal Title: Chem.Asian J. 4 Pages: 574-580
  • Peer Reviewed
• [Journal Article] Synthesis of diaminopimelic acid containing peptidoglycan fragments and tracheal cytotoxin (TCT) and 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] 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.Jpn. BCSJ Award article 81 Pages: 796-819
  • Peer Reviewed
• [Journal Article] A submicrogram scale protocol for biomolecule-based PET imaging by rapid 6π-azaelectrocyclization : visualization of sialic acid dependent circulatory3 residence of glycoproteins. (2008)
  • Author(s): Tanaka, K., Masuyama, T., Hasegawa, K., Tahara, T., Mizuma, H., Wada, Y., Watanabe, Y., Fukase, K.
  • Journal Title: Angew.Chem.Int.Ed. 47 Pages: 102-105
  • Peer Reviewed
• [Presentation] 特別企画講演:標的指向型ライブラリー構築と生命科学への貢献 (2011)
  • Author(s): 深瀬浩一
  • Organizer: 日本化学会第91回春季年会
  • Place of Presentation: 神奈川大学
  • Year and Date: 20110326-20110329
• [Presentation] 学術賞受賞講演:精密有機合成と生体イメージングを基盤とする生物活性複合糖質の機能解明 (2011)
  • Author(s): 深瀬浩一
  • Organizer: 日本化学会第91回春季年会
  • Place of Presentation: 神奈川大学
  • Year and Date: 20110326-20110329
• [Presentation] Synthetic approach for in vivo functional studies of glycans : Application of PETimaging (2010)
  • Author(s): 深瀬浩一
  • Organizer: The 2010 InternationalChemical Congress of Pacific Basin Societies(Pacifichem 2010)
  • Place of Presentation: Honolulu, USA, Invited
  • Year and Date: 20101214-20101220
• [Presentation] Study of microfluidic reactionstoward production of biofunctional molecules : Application to glycan synthesis (2010)
  • Author(s): 深瀬浩一
  • Organizer: The 2010 International Chemical Congress of PacificBasin Societies (Pacifichem 2010)
  • Place of Presentation: Honolulu, USA, Invited
  • Year and Date: 20101214-20101220
• [Presentation] Synthetic Approach for Elucidating Glycan Codes (2010)
  • Author(s): Koichi Fukase, Yukari Fujimoto, Katsunori Tanaka
  • Organizer: The 5th InternationalConference on Cutting-Edge Organic Chemistryin Asia (ICCEOCA-5)
  • Place of Presentation: Hsinchu, Taiwan, Invited
  • Year and Date: 20101107-20101111
• [Presentation] Synthetic Approach toward Understanding In Vivo Functions of Glycans (2010)
  • Author(s): 深瀬浩一
  • Organizer: The 25th International CarbohydrateSymposium (ICS 2010)
  • Place of Presentation: Makuhari Messe(Chiba), Invited
  • Year and Date: 20100801-20100806
• [Presentation] Synthesisof new probes for chemical glycobiology : application to PET and fluorescent imaging of glycoproteins, glycoclusters, and living cells (2009)
  • Author(s): Koichi Fukase, Katsunori Tanaka, TatsuroMasuyama, Kaori Minami, Eric R.O. Siwu, KokiHasegawa, Tsuyoshi Tahara, Hiroshi Mizuma, Yasuhiro Wada, Yasuyoshi Watanabe
  • Organizer: The Second International Symposium on Combinatorial Sciences in Chemistry, Biology,Catalysts and Materials (SCS09)
  • Place of Presentation: Beijin, China, Invited
  • Year and Date: 20090919-20090923
• [Presentation] 有機合成で生物機能に迫る:マイクロフロー合成と固相合成による糖鎖構築と糖鎖の新機能解析 (2009)
  • Author(s): 深瀬浩一
  • Organizer: 第29回日本糖質学会年会
  • Place of Presentation: 世界生活文化センター(岐阜県)招待講演
  • Year and Date: 20090909-20090911
• [Presentation] Molecular Probe Method for Studying the Biofunctional Role of Glycoconjugates (2009)
  • Author(s): 深瀬浩一
  • Organizer: The 25th Naito Conference, Chemical Biology II-An Emerging Filed Inspired by Natural Product Chemistry-
  • Place of Presentation: Shateraise Gateaux Kingdom Sapporo (Hokkaido), Invited
  • Year and Date: 20090908-20090911
• [Presentation] 糖鎖の合成とin vivo生体分子科学 (2009)
  • Author(s): 深瀬浩一
  • Organizer: 第44回天然物化学談話会
  • Place of Presentation: つくばグランドホテル(茨城県)(招待講演)
  • Year and Date: 20090708-20090710
• [Presentation] Chemical Glycobiology of Self/Non-self Recognition (2009)
  • Author(s): 深瀬浩一
  • Organizer: Gordon Research Conferences, Carbohydrates
  • Place of Presentation: Tilton School, Tilton, NH,Invited
  • Year and Date: 20090614-20090619
• [Presentation] シンポジウム「ケミカルバイオロジー研究の最前線-新分野としての未来-」自己と非自己の認識に関するケミカルグリコバイオロジー (2009)
  • Author(s): 深瀬浩一
  • Organizer: 日本化学会第89春季年会
  • Place of Presentation: 日本大学(千葉県)(招待講演)
  • Year and Date: 20090327-20090330
• [Presentation] 集積型合成を目指したマイクロフロー合成研究:フロー・マイクロ合成研究会第4回銅金賞受賞講演 (2009)
  • Author(s): 深瀬浩一
  • Organizer: フロー・マイクロ合成研究会第21回公開講演会
  • Place of Presentation: 大阪科学技術センター
  • Year and Date: 2009-08-07
• [Presentation] 有機合成で生物機能に迫る:マイクロフロー合成と固相合成による糖鎖構築と糖鎖の新機能解析 (2009)
  • Author(s): 深瀬浩一
  • Organizer: 第34回有機反応懇談会
  • Place of Presentation: 関西学院大学(招待講演)
  • Year and Date: 2009-08-03
• [Presentation] Chemical synthesis of bacterial PAMPs for elucidation and regulation of innate immune response (2008)
  • Author(s): 深瀬浩一
  • Organizer: 10th Biennial Meeting of the International Endotoxin and Innate Immunity Society (IEIIS2008)
  • Place of Presentation: Edinburgh, UK, Invited
  • Year and Date: 20080730-20080802
• [Presentation] ペプチド・タンパク質、抗体の革新的標識法とPETによる動態解析への応用 (2008)
  • Author(s): 深瀬浩一
  • Organizer: 第2回ミニシンポジウムバイオ医薬品のマイクロドーズ・早期探索臨床試験の意義と課題、医薬品開発支援機構(APDD)・マイクロドーズ・探索臨床試験研究会共催
  • Place of Presentation: 東京大学薬学部(招待講演)
  • Year and Date: 2008-08-09
• [Presentation] 化学合成で糖鎖の生物機能を解析する (2008)
  • Author(s): 深瀬浩一
  • Organizer: 理研シンポジウム第3回有機合成化学のフロンティア
  • Place of Presentation: 理化学研究所和光研究所(埼玉県)(招待講演)
  • Year and Date: 2008-07-07
• [Book] Self and nonself recognition with bacterial and animal glycans, surveys by synthetic chemistry, Methods in Enzymology (2010)
  • Author(s): Fujimoto, Y., Tanaka, K., Shimoyama, A., Fukase, K.
  • Total Pages: 478(323-342)
• [Remarks] ホームページ
  • URL: http://www.chem.sci.osaka-u.ac.jp/lab/fukase/
• [Patent(Industrial Property Rights)] リジンデンドリマー型糖鎖クラスターの製造法とその応用 (2009)
  • Inventor(s): 深瀬浩一、田中克典、渡辺恭良、小山幸一
  • Industrial Property Rights Holder: 国立大学法人大阪大学、独立行政法人理化学研究所、キシダ化学株式会社
  • Industrial Property Number: PCT/JP2009,080637
  • Filing Date: 2009-03-27