方案摘要
方案下载应用领域 | 制药/生物制药 |
检测样本 | 化药新药研发 |
检测项目 | 其他>方法开发 |
参考标准 | 无 |
加压毛细管电色谱(pCEC)是综合了高效液相色谱(HPLC)与毛细管电泳(CE)的优势而发展起来的一种高效微型分离技术,在继承了液相色谱的高选择性以及毛细管电泳的高效率特性的基础上,克服了毛细管电泳难以分离中性物质的缺陷,同时解决了微小颗粒固定相由于输液泵的耐压能力在常规HPLC中的应用限制。 本文是利用加压毛细管电色谱技术进行手性分离的应用文章。
NG-nitro-D-arginine (D-NNA), i.v. injected into rats, produced apressor response, and was presumed to act via chiral inversioninto NG-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase.We examined the possible role of renal D-amino acid
oxidase (DAAO) in the chiral inversion of D-NNA to L-NNA. Inpentobarbital-anesthetized rats, L-NNA was detected via capillary electrochromatography in the blood immediately after i.v.injection of D-NNA. The time course of appearance of L-NNAparalleled the increase in blood pressure elicited by D-NNA. Unilateral renal ligation partially, and bilateral ligation completely,blocked the pressor response as well as the conversionof D-NNA to L-NNA. Furthermore, injection into conscious rats
of sodium benzoate, a selective DAAO inhibitor, completely blocked the pressor response to naive D-NNA, but not pressor response to D-NNA preincubated with homogenates of the kidney. Homogenates of the kidneys, liver (lesser degree), and
brain (much lesser degree) converted D-NNA to L-NNA, and the chiral inversion was blocked by the addition of benzoate. Moreover,D-NNA chiral inversion correlates with the activity of DAAO. Our results reveal a novel pathway of chiral inversion of D-amino acids where the renal DAAO plays an essential role that accounts for the biological activity of D-NNA.
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