| Project/Area Number |
11672114
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Tokyo University of Agriculture and Technology |
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Principal Investigator |
KAJIMOTO Tetsuya Tokyo University of Agriculture and Technology, Department of Engineerinng, associate Prof., 工学部, 助教授 (80185777)
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| Co-Investigator(Kenkyū-buntansha) |
MIURA Tsuyoshi Tokyo University of Agriculture and Technology, School of Pharmacy Showa University assistant prof., 薬学部, 助手 (40297023)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | porcine liver / hyper acute rejection / Galα (1,3) Gal / ycestericin D / β-hydroxy-α-L-amino acid / α1, 3-galactosyltransferase / UDP-galactose / inhibitor / Galα(1,3)Gal糖鎖 / β-ヒドロキシ-α-L-アミノ酸 / N-アセチルガラクトサミニダーゼ / 肝臓移植 / セラミド類似体 / D-スレオニンアルドラーゼ / galactosyl α(1-3)galactose / α-D-ガラクトシダーゼ阻害 / 1,4-dideoxy-1,4-imino-D-lyxitol / L-スレオニンアルドラーゼ |
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| Research Abstract |
It is known that hyper acute rejection (HAK) which interfere with the xeno-transplantation of organs was caused by excess immune responses between Gala (1,3) Gal antigenic glycoside of porcine liver and the antibody generated in the recipient serum toward the glycoside. In order to develop the novel medical materials for avoiding the HAR, we synthesized mycestericin D and F, potent immune suppressants isolated from Isaria sinclairii, and a UDP-galactose mimetic as an inhibitor of α1,3-galactosyltransferase that biosynthesizes the Galaα(1,3) Gal epitope.
1) Synthesis of mycestericins
γBenzyloxybutanal was treated with L-threonine aldolase (from Candida humicola AKU 4586) that catalyzes aldol condensation in the presence of glycine to afford the ε-benzyloxy-α-L-amino acid, of which the methyl ester was transformed to an oxazoline derivative by the reaction with methyl benzimidate. After addition of the C-l unit to the α-orposition of the oxazoline derivative, of which the benzyl ether was transformed to an aldehyde group, the following Wittig reaction and deprotection gave mycestericin D. A subsequent hydrogenation step gave mycestericin F.
2) Synthesis of peptidic mimetics of UDP-galactose
L-Threonine aldolase-catalyzed reaction of 2-(l-N-uracily])acetaldehyde and glycine afforded a uracil residue bearing β-hydroxy-α-L-amino acid, of which the benzyl ester was condensed with 2-(l-O-α-galactosyl) hydroxyacetic acid by the DCC / HOBt method to form a peptidic linkage. The following deprotection procedure provided the peptidic mimetics of UDP-galactose.
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