| Project/Area Number |
61571029
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Physical pharmacy
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
KURODA Yoshihiro Kyoto University Tutor, 薬学部, 助手 (90093236)
|
|---|
| Project Period (FY) |
1986 – 1988
|
| Project Status |
Completed (Fiscal Year 1988)
|
| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1988: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,000,000 (Direct Cost: ¥1,000,000)
|
|---|
| Keywords | Two-dimensional NMR / Window Function / Nuclear Overhauser Effect / Lipid Bilayer Vesicles / Spin Diffusion / Local Anesthetic / Tetracaine / ウィンドウ関数 / サインベル関数 / フォスファチジルコリン / 膜の運動性 / 関数処理 |
|---|
| Research Abstract |
Two-dimensional nuclear magnetic resonance spectroscopy has been applied for studying the interactions between membranes and drugs. In dealing with the free induction decay signals obtained from a tow-dimensional NOE experiment, window functions were found to be used with the greatest possible care. This is due to the broad NMR peaks in the drug-membrane system. Although a Lorentzian to Gaussian transformation function is known to be useful in enhancing the resolution of an NMR spectrum of a low-molecular-weight molecule which can afford relatively narrow NMR resonance peaks, the function often fails to yield a good line shape or contour map in the case where there exist broad resonance peaks harious line widths. A careful choice of the parameters relevant to the function is required.
Two-dimensional NOE experiments for dibucaine hydrochloride-egg phosphatidylcholine(PC) vesicles solution showed that dibucaine is located only at the outer half of the bilayer vesicles. The reason why the dibucaine reside only at the outer half of the bilayer can be ascribed to the packing asymmetry due to the small radius of curvature of the vesicle bilayer.
The problems accompanied by the presence of buffer materials in the interactions between dibucaine or tetracaine and small unilamellar PC vesicles have been investigated. The two-dimensional noe experiments showed that the conformation of dibucaine varies depending on the presence of buffer and also on the pH of the sample solution. Tetracaine showed some minor components in its H-1 NMR spectrum when it was dissolved in an acetate buffer solution. The minor components have been ascribed to the tetracaine of strongly bound species which locate in the bilayer deeper than the major components which revealed relatively sharp NMR peaks.
|
