Project/Area Number |
13557207
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Biological pharmacy
|
Research Institution | University of Shizuoka |
Principal Investigator |
SUZUKI Yasuo University of Shizuoka School of Pharmaceutical Sciences, Biochemistry, Professor, 薬学部, 教授 (00046278)
|
Co-Investigator(Kenkyū-buntansha) |
USUI Taichi University of Shizuoka, Applied Biological Chem., Prof., 農学部, 教授 (50111802)
KANIE Osamu Mitsubishi Kagaku Inst. Life Sciences, Chief Investigator, 主任研究員
KOBAYASHI Kazukiyo Nagoya University, Dept. Molecular Design, Prof., 大学院・工学研究科, 教授 (10023483)
レカ ラジュネジャ 太陽化学株式会社, NF事業部, 研究開発・部長
LEKH Raj junejar Taiyo Kagaku Co. Ltd., Int. Dept., Director
レカ・ラ ジュネジャ 太陽化学(株), NF事業部, 部長(研究職)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2002: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2001: ¥8,700,000 (Direct Cost: ¥8,700,000)
|
Keywords | Influenza Virus / Anti-Influenza Drug / Hemagglutinin / Nueraminedase / Anti-Viral Drugs / Receptor / Ganglioside / Sensor / センター / シアリダーゼ / 宿主域 / インフルエンザ |
Research Abstract |
1. The discovery of a new sialocompound which blocks both process of the entry into and release from the host cells of influenza viruses: Neu5Ac3 α F-distearoylphoshatidy lethanolamine in which the C-3 position was modified with an axial fluorine atom, was found to inhibit the catalytic hydrolysis of influenza virus sialidase and the binding activity of hemagglutinin. The inhibitory activities to sialidases were independent of virus isolated examined. The study suggested that the compound is a bew class of bifunctional drug candidates for the future chemotherapy of influenza. 2. Tris-bipyridine ruthenium-complex carrying a disialo complex-type oligosaccharide were prepared via a one-pot transglycosylation using endo-glycosidase (Endo M); they bind to type-A influenza viruses with excellent affinity (IC50 = 8.4 μM), and their luminescence intensity is strongly depressed by virus-binding. This result indicate that the resulting ruthenium-cpmplex is applicable to a new influenza-sensory system. 3. A new sialo-glycosphingolipid (Ganglioside) which binds and strongly inhibits the infection of every human and animal influenza viruses tested was found in and isolated from embryonate chicken eggs. A part of the chemical structure was determined by the analyses of Mass spectrometry. It is suggested that this ganglioside may be one of the real endogenous receptor molecule for influenza viruses in nature. This derivative may applicable to develop a strong anti-influenza drugs in future. 4. Several native and synthesized compounds such as artificial mucin carrying sialyllacto-series sugar chain, or cyclic peptide to which sialyllactose connected were found to inhibit the influenza replication.
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