SOLVENT DEPENDENCE OF ENZYME ENANTIOSELECTIVITY

本研究的目的是提高综合范围提供的 在有机溶剂中的酶催化，用于不对称转化 导致生物医学化合物的合成。 非水介质中酶催化的机理及影响因素 或有机溶剂对酶结构的影响尚不清楚。作为 结果，酶的选择性（前手性选择性和 对映选择性）的任何给定的反应不能预测，和 因此，不能使用有机溶剂中的酶催化 有效和成功地实现上述目的。 本研究的目的是：（a），确定 酶催化在有机溶剂中，通过研究有机溶剂的影响， 溶剂对枯草杆菌蛋白酶C结构的影响，通过研究 影响酶的溶剂的物理化学性质 对映选择性;（B），研究性质（增强 对映体选择性、稳定性和催化速率）的枯草杆菌蛋白酶C.- 在有机溶剂中的环糊精混合物。这种新的酶制剂 已经显示出具有较高的反应速率和对映选择性， 并在冻干过程中保持酶的二级结构 （初步结果）。因此，它有可能成为 酶制剂的选择，用于合成生物医学相关的 化合物.这个项目的最终目标是找到一个系统， 任何给定反应的酶对映选择性可以是 在任何溶剂中合理预测。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

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.