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Molecular-reorientational dynamics investigation of biomolecules in solution by NMR, X-ray and CSI-MS.

通过 NMR、X 射线和 CSI-MS 对溶液中的生物分子进行分子重定向动力学研究。

基本信息

批准号：
16590002
负责人：
SEKI Hiroko
金额：
$ 1.6万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590002/
关键词：
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

项目摘要

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.

1 .通过PFG NMR、CSI-MS对稀释溶液中的类固醇化合物氢键进行了广泛的分析，并通过x射线晶体分析对固态中的类固醇化合物进行了氢键分析。虽然晶体x射线分析和溶液中CSI-MS测量表明甾体化合物的扩散系数D_<obs>可能随氢键数的变化而变化，但通过扩散研究确定的实际观察值D_<obs>值不断减小，与氢键数的减少没有相关性。基于类固醇化合物分子间氢键的链式结构（簇）的形成得到了明确的证实。为了证实这一前所未有的现象，我们进行了PFG核磁共振扩散研究。通过PFG核磁共振测量得到BG + nBA （n=1 ~ 4）的D值，包括BG和BA本身。观察到的D值随附着BA (n)的增加而减小。这一结果清楚地支持了csi - ms - iii观察到的配合物在溶液中的有序形成。发现^<19>F{^1H} NOE和2D ^1H-<-19>F HOESY实验检测到氟烷^<19>F和HSA质子之间的分子间NOE。通过^1H和^<19>F NMR测量了氟烷的扩散系数，表明氟烷与HSA的相互作用。目前的结果表明，这些技术非常适合在药物发现过程中鉴定与蛋白质受体结合的含氟配体。基于差分扩散的核磁共振技术可以使用简单的脉冲序列直接检测复合物中的配体信号，而无需同位素标记。目前的结果表明，这些技术非常适合在药物发现过程中识别与蛋白质受体结合的配体。

项目成果

期刊论文数量（60）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Application of the ^19F NMR Technique to Observe Binding of the General Anesthetic Halothane to Human Serum Albumin

应用^19F NMR技术观察全身麻醉药氟烷与人血清白蛋白的结合

DOI：
10.2116/analsci.20.1475
发表时间：
2004
期刊：
Analytical Sciences
影响因子：
1.6
作者：
Kazuaki Shikii;S. Sakurai;H. Utsumi;H. Seki;M. Tashiro
通讯作者：
M. Tashiro

Identification of 2-(cysteinyl)amido-2-deoxy-D-galacturonic acidresidue from the sheath of Leptothrix cholodnii

科氏细毛菌鞘中2-(半胱氨酰)酰胺基-2-脱氧-D-半乳糖醛酸残基的鉴定

DOI：
发表时间：
2006
期刊：
Biosci.Biotech.& Biochem 70
影响因子：
0
作者：
Makita;H.;Nakahara;Y.;Fukui;H.;Miyanoiri;Y.;Katahira;M.;Seki;H.;Takeda;M.and Koizumi;J.
通讯作者：
J.

Crystal Structure of 1-Butyl-3-methylimidazolium Iodide

DOI：
10.1246/cl.2006.1400
发表时间：
2006-11
期刊：
Chemistry Letters
影响因子：
1.6
作者：
M. Nakakoshi;M. Shiro;T. Fujimoto;T. Machinami;H. Seki;M. Tashiro;K. Nishikawa
通讯作者：
M. Nakakoshi;M. Shiro;T. Fujimoto;T. Machinami;H. Seki;M. Tashiro;K. Nishikawa

Anomalous dynamic behavior of ions and water molecules in dilute aqueous solution of 1-butyl-3-methylimidazolium bromide studied by NMR