Project/Area Number |
06557118
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 試験 |
Research Field |
Chemical pharmacy
|
Research Institution | THE UNIVERSITY OF TOKYO |
Principal Investigator |
HASHIMOTO Yuichi THE UNIVERSITY OF TOKYO,Insititute of Molecular and Cellular Biosciences Associate Professor, 分子細胞生物学研究所, 助教授 (90164798)
|
Co-Investigator(Kenkyū-buntansha) |
MORISAKI Naoko THE UNIVERSITY OF TOKYO,Insititute of Molecular and Cellular Biosciences Assista, 分子細胞生物学研究所, 助手 (00092354)
SHIRAI Ryuichi THE UNIVERSITY OF TOKYO,Insititute of Molecular and Cellular Biosciences Assista, 分子細胞生物学研究所, 助手 (80183838)
IWASAKI Shigeo THE UNIVERSITY OF TOKYO,Insititute of Molecular and Cellular Biosciences Profess, 分子細胞生物学研究所, 教授 (00013326)
|
Project Period (FY) |
1994 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥8,900,000 (Direct Cost: ¥8,900,000)
Fiscal Year 1996: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
|
Keywords | dextran / intercalator / retinoid / porphyrin / affinity labeling / nucleic acid / receptor / tumor promoter / 分子認識 / インターカレーション / ジヌクレオチド / 塩基選択性 / 水溶性ポリマー / ヘミン |
Research Abstract |
Behavior in hydrophyilic circumstances of lipid biofactors which control gene expression and sell proliferation was analyzed. Various lipid biofactors including DNA-intercalators, retinoids, tumor promoters, and nuclobases were selected as molecules which to be analyzed. They were converted to water-soluble materials by the dextran-coupling method and/or the usage of the mirror-image nucleosugar. Selected compounds were polyfunctionalized by introducing fluorescent and/or photolabile functioal groups. Analysis using the intercalator-dextran method revealed non-intercalative base-selective interaction of the intercalator and mono/di-nucleotides. Analysis using the mirror-image nucleosugar, i. e., enantio/meso-DNAs, revealed the characteristic interactions of these pseudo-DNAs with the complementary natural nucleic acids. The results suggest that these pseudo-DNAs can be lead compounds for new antisense/antigene molecules. Development of fluorescent/photolablile synthetic retinoids reached to the elucidation of the sites in nuclear retinoic acid receptor's ligand binding domain at which the ligand directly interacts. Similar technique applied on tubulin disruptors revealed the sites in tubulin protein at which the disruptors directly interact. Preparation of affinity gels liganded with tumor promoters reached the purification of the putative specific tumor promoter receptor whose structural identification is under progress.
|