Analysis of cell surface glycan networks to elucidate the function of glycan posttranslatinal modification on membrane proteins
Project/Area Number |
16H05924
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Biomolecular chemistry
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Research Institution | Osaka University |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000)
Fiscal Year 2019: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
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Keywords | 糖鎖合成 / 糖鎖修飾 / 免疫 / ケミカルバイオロジー / N-グリカン / 糖鎖 / 複合化 / レクチン / 糖鎖機能解明 / イメージング / HaloTag / コアフコース |
Outline of Final Research Achievements |
Asparagine-linked oligosaccharides (N-glycans) on glycoproteins have high diversity and complexity and are involved in a variety of important physiological events. We achieved the synthesis of several complex type N-glycans, including core fucos containing N-glycan, bisecting GlcNAc containing N-glycan, and poly lactosamine containing N-glycans. We carried out live cell imaging using HaloTag to elucidate the function of N-glycans on membrane proteins. We prepared HaloTag-expressing cells and presented synthetic glycans. Then, we succesfully demonstrated that the interaction between glycans and lectins can regulate the dynamics of membrane proteins. Furthermore, we discovered the lectin recognizing core fucose. In addition, we also developed effective cancer vaccines with focusing on the relationship between glycan and immunity.
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Academic Significance and Societal Importance of the Research Achievements |
一部の可溶性タンパク質の修飾糖鎖に関しては,その機能発現機構が解明されつつあるが,膜タンパク質については,その糖鎖構造に基づく機能解析は進んでいない.本研究では,N-グリカンの化学合成を達成し,Tagテクノロジーにより,厳密に糖鎖構造を制御したモデル膜タンパク質を調製し,膜タンパク質における糖鎖の機能の一端を明らかにし,膜タンパク質における糖鎖機能解明の大きな一歩である.N-グリカンによる膜タンパク質の機能制御が,がんなどのさまざまな疾病と関連することから,糖鎖機能の制御という新しい概念に基づいた創薬につながる可能性もある.また,糖鎖機能解明の新しい方法論を提案したという点でも意義が大きい.
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Report
(5 results)
Research Products
(116 results)
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[Journal Article] α‐Emitting cancer therapy using 211 At‐AAMT targeting LAT12021
Author(s)
Kaneda‐Nakashima Kazuko、Zhang ZiJian、Manabe Yoshiyuki、Shimoyama Atsushi、Kabayama Kazuya、Watabe Tadashi、Kanai Yoshikatsu、Ooe Kazuhiro、Toyoshima Atsushi、Shirakami Yoshifumi、Yoshimura Takashi、Fukuda Mitsuhiro、Hatazawa Jun、Nakano Takashi、Fukase Koichi、Shinohara Atsushi
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Journal Title
Cancer Science
Volume: 112
Issue: 3
Pages: 1132-1140
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Unveiling Molecular Recognition of Sialoglycans by Human Siglec-102020
Author(s)
Forgione Rosa Ester、Di Carluccio Cristina、Guzman-Caldentey Juan、Gaglione Rosa、Battista Filomena、Chiodo Fabrizio、Manabe Yoshiyuki、Arciello Angela、Del Vecchio Pompea、Fukase Koichi、Molinaro Antonio、Martin-Santamaria Sonsoles、Crocker Paul R.、Marchetti Roberta、Silipo Alba
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Journal Title
iScience
Volume: 23
Issue: 6
Pages: 101231-101231
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Synthesis And Immunological Evaluation of Self-adjuvanting Anticancer Vaccine Candidate.2019
Author(s)
Manabe, Y., Chang, T-C., Feng, Q., Fujimoto, Y., Ohshima, S., Kametani, Y., Kabayama, K., Nimura, Y., Lin, C-C., Fukase, K.
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Journal Title
Peptide Science
Volume: 2019
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Branched Sialylated <i>N</i>-glycans Are Accumulated in Brain Synaptosomes and Interact with Siglec-H2018
Author(s)
M. Handa-Narumi, T. Yoshimura, H. Konishi, Y. Fukata, Y. Manabe, K. Tanaka, G.-m. Bao, H. Kiyama, K. Fukase, K. Ikenaka
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Journal Title
Cell Structure and Function
Volume: 43
Issue: 2
Pages: 141-152
DOI
NAID
ISSN
0386-7196, 1347-3700
Related Report
Peer Reviewed / Open Access
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[Journal Article] Synthesis and Functional Studies of Self-Adjuvanting Cancer Vaccine Containing B Cell Epitope Derived from HER2.2017
Author(s)
Feng, Q., Kabayama, K., Manabe, Y., Miyamoto, A., Kametani, Y., Fukase, K.
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Journal Title
Peptide Science
Volume: 2017
Pages: 56-57
Related Report
Peer Reviewed
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[Journal Article] Development of alpha1,6-fucosyltransferase inhibitors through the diversity-oriented syntheses of GDP-fucose mimics using the coupling between alkyne and sulfonyl azide.2017
Author(s)
Manabe, Y., Kasahara, S., Takakura, Y., Yang, X., Takamatsu, S., Kamada Y., Miyoshi, M., Yoshidome, D., Fukasea, K.
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Journal Title
Bioorg. Med. Chem.
Volume: in press
Issue: 11
Pages: 2844-2850
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Presentation] Immunological Evaluation of Conjugate/Co-Assembly of Peptide Antigen and Adjuvant as Self-adjuvanting Anti-breast Cancer Candidates2020
Author(s)
Keita Ito, Yoshiyuki Manabe, Taku Aiga, Tsung-Che Chang, Kazuya Kabayama, Shino Ohshima, Yoshie Kametani, Hiroto Furukawa, Hiroshi Inaba, Kazunori Matsuura, and Koichi Fukase
Organizer
第57回ペプチド討論会
Related Report
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