| Project/Area Number |
09660115
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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 |
Bioproduction chemistry/Bioorganic chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
ICHIKAWA Yoshiyasu Nagoya University, School of Agricultural Sciences Associate Professor, 農学部, 助教授 (60193439)
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| Co-Investigator(Kenkyū-buntansha) |
ISOBE Minoru Nagoya University, School of Agricultural Sciences Professor, 農学部, 教授 (00023466)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | tautomycin / protein phosphatase / inhibitor / amino sugars / D-perosamine / antigenic LPS / antibiotic / methyl-beta-D-vicenisaminide |
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| Research Abstract |
1) Improved method for the esterification of each segment in the synthesis of tautomycin have been developed. Use of the diol segment B/C have bee achieved in better and more efficient manner. This method pave the way to the synthesis of the tautomycin derivatives for the search of the mechanism and action of protein phosphatase-inhibitor interactions.
2) The synthesis of tautomycin-okadaic acid hybrid molecule have been explored with the search of the mechanism and action of protein phosphatase-inhibitor interactions in mind. Coupling reaction of segment C of okadaic acid with segment B of tautomycin followed by the efficient esterification developed above provided the tautomycin-okadaic acid hybrid molecule. Inhibition assay of the tautomycin-okadaic acid hybrid molecule revealed that the hybrid molecule inhibits PP2A more effectively than PP1. This result strongly suggested that design of inhibitor specific to each protein phosphatase is possible by using molecular recognition.
3) A n
… More
ew approach for the synthesis of amino sugars using an allyl cyanate-to-isocyanate rearrangement has been developed. The key feature in this method involves introduction of the nitrogen substituents into the pyranose framework by [3,3] sigmatropic rearrangement of an allyl cyanate. Subsequent functionalization of the allyl amine moiety by either hydroxylation or cyclofunctionalization completed the synthesis of two amino sugars, D-perosamine and D-vicenisamine. 4-Amino-4,6-dideoxy-D-mannose (D-perosamine) was first discovered in a polyene macrolide antibiotic perimycin and was later recognized the presence in the lipopolysaccharide (LPS) of Vivrio cholera 569B (Inaba). Further investigation revealed that N-formylated-D-perosamine was a component of a repeating pentasaccharide unit in O-chains of the LPS of Yersinia enterocolitica and Brucella abortus. These findings established a molecular basis for extensive serological cross-reactivity between the antigenic LPS.Structual studies of vicenistatin isolated from Streptomyces sp. HG 34 as a new antitumor antibiotic revealed that vicenistatin contains an amino sugar vicenisamine. Degradation study by Shindo et al. showed that methanolysis of vicenistatin yielded the methyl-beta-D-vicenisaminide. Less
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