DEVELOPMENT OF RNA ANALOG INHIBITORS AGAINST VERO TOXIN PRODUCED BY E. COLI
| Project/Area Number |
11680594
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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 |
Bioorganic chemistry
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| Research Institution | Kinki University |
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Principal Investigator |
FUJII Masayuki KINKI UNIVERSSITY, KYUSHU SCHOOL OF ENGINEERING, PROFESSOR, 九州工学部, 教授 (60199297)
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| Co-Investigator(Kenkyū-buntansha) |
, 教授
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Vero toxin / 28SrRNA / RNA analogs / therapeutic agents / 28S rRNAアナログ / 阻害剤 / RNAデコイ |
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| Research Abstract |
Synthesis and characterization of specific inhibitor and detection probe of vero toxin (VT) produced by enterobacterium O-157 were studied. Molecular design based on detail analysis of reaction mechanisms of N-glycosidase activity of vero toxin was performed. Analogous molecules of 28S rRNA which is a substrate for vero toxin A chain and globotriose (Gb3) ceramide which is a glycoreceptor on cell surface for vero toxin B chain. Inhibitory effects of some analogous RNA molecules which have GAGA tetraloop structure in common were evaluated by conventional experiments and showed that 2'-OMe anaolgs and phosphorothioate analogs were promising structure for drug application because those structures are known to be stable in physiological conditions in cells and even in vivo. Gb3 analogs bearing biotin moiety were prepared and immobilized on SPR sensor tip. Obsevations of binding affnities of the Gb3 analogs and abrin C which has the same specificity of sugar binding as vero toxin suggested that synthesized analogs were good detection probes for vero toxin. Fluorecein labeled Gb3 analogs and some other sugar derivatives were revealed that they are also good probes for the detection of VT using a fluorospectrometer.
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Report
(4 results)
Research Products
(30 results)
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[Publications] Takanori Kubo, Kinuko Yokoyama, Ryoji Ueki, Shinya Abe, Koichiro Goto, Takuro Niidome, Haruhiko Aoyagi, Kaoru Iwakuma, Setsuko Ando, Shin Ono and Masayuki Fujii: "Design, Systhesis and Characterization of DNA Binding Peptides"Peptide Science. 2000. 109-112 (2001)
Description
「研究成果報告書概要(欧文)」より
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