Synthetic study of bypass-like glycans as therapeutic agent for muscular dystrophy
Project/Area Number |
15K01823
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Chemical biology
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Research Institution | Tottori University |
Principal Investigator |
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Research Collaborator |
TAMURA takahiro
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Project Period (FY) |
2015-10-21 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | ジストログリカン / バイパス糖鎖 / 糖鎖合成 / 筋ジストロフィー |
Outline of Final Research Achievements |
Matriglycan strongly interacts with laminine to form muscular tissue. In this study, the oligosaccharide which composes matriglycan was chemically synthesized and we clarified the facile structure. In addition, we regio- and stereoselectively synthesized xylosyl ribitolphosphate which locates at the reducing side of matriglycan at the first time. NMR data of the chemically synthesized compound was compatible with those of natural product. The xylosyl ribitolphosphate will be a primer of the enzymatic glycan elongation to form bypass-like glycans as therapeutic agent for muscular dystrophy.
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Academic Significance and Societal Importance of the Research Achievements |
糖鎖異常型筋ジストロフィーは、基底膜上のラミニンと細胞膜上のαジストログリカンを連結する糖鎖(マトリグリカン:MG)が正常に生合成されないため発症する有効な治療方法のない難病である。本研究ではMGの構成オリゴ糖の化学合成に成功した。一方、MGの還元側に位置するキシロシルリビトールリン酸の合成にも成功し、天然物の構造決定を検証するとともに、MGの酵素的伸長のプライマー候補を得た。MGの化学的再構築によりバイパス化合物の合成に道筋をつけた。この化合物が糖鎖医薬として実証されれば、ポスト遺伝子治療として医学薬学的に大きな波及効果が期待できる。
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Report
(5 results)
Research Products
(57 results)
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[Journal Article] Glycan sulfation patterns define autophagy flux at axon tip through PTPRs-cortactin axis2019
Author(s)
Kazuma Sakamoto, Tomoya Ozaki, Yen-Chun Ko, Cheng-Fang Tsai, Yuanhao Gong, Masayoshi Morozumi, Yoshitomo Ishikawa, Kenji Uchimura, Satomi Nadanaka, Hiroshi Kitagawa, Medal Manuel L. Zulueta, Anadaraju Bandaru, Jun-ichi Tamura, Shang-Cheng Hung, and Kenji Kadomatsu
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Journal Title
Nature Chemical Biology
Volume: -
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Synthesis of chondroitin sulfate CC and DD tetrasaccharides and interactions with 2H6 and LY111.2018
Author(s)
Matsushita, K., Nakata, T., Takeda-Okuda, N., Nadanaka, S., Kitagawa, H., and Tamura, J.
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Journal Title
Bioorg. Med. Chem.
Volume: 26
Issue: 5
Pages: 1016-1016
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] ANALYTICAL STUDY OF CHONDROITIN SULFATE IN DEER ANTLER2018
Author(s)
Jun-ichi Tamura, Asumi Uemura, Yuga Inoue, Daiki Sugita, Yuka Omura, Yuna Uemura, Marin Mitani, Akari Tani, Byong-tae Jeon, Chi-ho Lee, Soo-ki Kim, and Naoko Takeda-Okuda
Organizer
XXth International Carbohydrate Symposium
Related Report
Int'l Joint Research
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