| Project/Area Number |
16590002
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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 | Chiba University |
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Principal Investigator |
SEKI Hiroko Chiba University, Chemical Analysis Center, Associate Professor, 分析センター, 助教授 (60114245)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | molecular interaction / diffusion / PFG NMR / CSI-MS / hydrogen bonding / steroid compounds / ionic liquid / Narcissistic / GSI-MS / クラスター / タンパク質-薬物複合体 |
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| Research Abstract |
I. An extensive analysis of hydrogen bonding of steroid compounds in diluted solution is preformed by PFG NMR, CSI-MS and in the solid state by X-ray crystallographic analysis. Although X-ray analysis in the crystalline state and CSI-MS measurement in solution suggested that the observed diffusion coefficient D_<obs> of the steroid compounds may vary in accordance with the number of hydrogen bonds, the actual observed D_<obs> value determined from the diffusion studies diminished constantly without correlation on the decreasing numbers of hydrogen bonds. Formation of a chain structure (cluster) based on intermolecular hydrogen bonding of the steroid compounds is unambiguously confirmed.
II. To confirm this unprecedented phenomenon in solution, we performed diffusion study by PFG NMR. The D values of the complexes BG + nBA (n=1〜4) including BG and BA itself, obtained by PFG NMR measurements. The observed D value decreases in accordance with the increasing number of attached BA (n). This result clearly supports the ordered formation of the complexes in solution as observed by CSI-MS.
III. It was found that ^<19>F{^1H} NOE and 2D ^1H-<-19>F HOESY experiments detected intermolecular NOEs between halothane ^<19>F and HSA protons. Measurements of diffusion coefficients for halothane were also carried out by ^1H and ^<19>F NMR, indicating the interaction of halothane with HSA. The present results indicate that these techniques are very suitable for identification of a fluorine containing ligand binding with a protein receptor in the drug discovery process.
IV. The difference diffusion-based NMR technique can directly detect the ligand signals from the complex using a simple pulse sequence without the need for isotope labeling. The present results indicate that these techniques are very suitable for identifying a ligand binding with a protein receptor in the drug discovery process.
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