SOLVENT DEPENDENCE OF ENZYME ENANTIOSELECTIVITY

酶对映选择性的溶剂依赖性

• 批准号: 6107319
• 负责人: GABRIEL Luis BARLETTA
• 金额: $ 17万
• 依托单位: UNIVERSITY OF PUERTO RICO AT HUMACAO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107319
• 关键词: catalyst; chemical reaction; chemical synthesis; computer simulation; enzyme activity; enzyme structure; fluorimetry; gas chromatography; gas chromatography mass spectrometry; infrared spectrometry; interferometry; lyophilization; nonwater solvent; organic chemicals; stereochemistry; stereoisomer; subtilisins

The goal of this study is to improve the synthetic scope afforded by enzymatic catalysis in organic solvents, for asymmetric transformation leading to the synthesis of biomedical compounds. The mechanism of enzyme catalysis in non-aqueous media, and the effect or organic solvents on the enzyme structure is not well understood. As a result, the enzyme selectivity (pro-chiral selectivity and enantioslectivity) of any given reactions can not be predicted, and therefore, enzyme catalysis in organic solvents can not be used efficiently and successfully for the purposes mentioned above. The objectives of this study are: (a), to determine the mechanism of enzyme catalysis in organ solvents, by studying the effect of organic solvents on the structure of subtilisin C., and by studying the physicochemical properties of the solvents which affect the enzyme enantioselectivity; (b), to study the properties (enhanced enantioselectivity, stability, and catalytic rate)of subtilisin C.- cyclodextrin mixtures in organic solvents. This new enzyme preparation has been shown to exhibit higher reaction rates and enantioselectivity, and to preserve the enzyme secondary structure during lyophilization (preliminary results). Therefore, it has the potential to become the enzyme preparation of choice for the synthesis of biomedical relevant compounds. The ultimate goal of this project is to find a system in which the enzyme enantioslectivity of any given reaction can be rationally predicted in any solvent. Enzyme catalysis in organ solvents will become a powerful tool for the syntheses of chiral biologically active compounds.

这项研究的目标是改善由 有机溶剂中的酶催化不对称转化 导致了生物医学化合物的合成。 酶在非水介质中的催化机理及其效果 或者有机溶剂对酶结构的影响还不是很清楚。作为一名 结果，酶的选择性(前手性选择性和 不能预测任何给定反应的对映选择性)，并且 因此，在有机溶剂中不能使用酶催化。 有效和成功地实现上述目的。 这项研究的目的是：(A)确定 酶在有机溶剂中的催化，通过研究有机物的影响 研究了不同溶剂对枯草杆菌毒素C结构的影响。 影响酶的溶剂的物理化学性质 对映体选择性；(B)，研究性质(增强 对映体选择性、稳定性和催化速率)。 有机溶剂中的环糊精混合物。这种新的酶制剂 已被证明具有更高的反应速率和对映体选择性， 并在冷冻干燥过程中保存酶的二级结构 (初步结果)。因此，它有可能成为 生物医药相关化合物合成中酶制剂的选择 化合物。这个项目的最终目标是在 任何给定反应的酶对映体选择性可以是 在任何溶剂中都能合理预测。有机溶剂中的酶催化 将成为手性生物合成的有力工具 活性化合物。