Dynamics and Function Relationships of Hydrolases in Organic Solvents

在规划生物活性有机分子的合成时越来越重要的考虑因素 是手性的引入。实现这一点的一种方法是使用手性催化剂，例如酶， 它们是高度对映性和特异性的，这一特征有助于制备靶手性手性化合物 具有药理活性的化合物。还有一个特性使这些生物催化剂对 有机化学家认为，它们的性质，如对映体选择性、前手性选择性和特异性是 由有机溶剂控制(当用作反应介质时)。奥索，酶很便宜，他们 可以“回收”，并且无毒。 不幸的是，有一些缺点限制了它们的应用和潜力。问题的根源 酶在非水介质中的催化机理还不是很清楚， 因此，通常需要一种试错法来寻找最佳的培养基、酶和条件。 本研究的目的是阐明有机溶剂影响酶的机制。 立体选择性、活性和稳定性，从而使立体选择性系统的合理设计成为可能 利用底物和溶剂的物理化学性质，以及酶的结构。我们 建议使用实验和理论相结合的方法(酶动力学，复杂 分子模拟和核磁共振方法)以了解介质在形成生物催化剂中的作用 结构、活性和立体选择性。

An increasingly important consideration when planning the synthesis of biological active organic molecules is the introduction of chirality. One method to achieve this is to use a chiral catalyst, such as an enzyme, which are highly enantiose/ective and specific, a feature that facilitates the preparation of target chirat pharmacologically active compounds. An additional property that makes these biocatalysts attractive to the organic chemist, is that their properties, such as enantioselectivity, prochiral selectivity and specificity are controlled by organic solvents (when used as the reaction medium). Olso, enzymes are inexpensive, they can be "recycled" and are non toxic. Unfortunately there are some drawbacks that limit their applications and potential. The root of the problem is that the mechanism of enzymatic catalysis in non-aqueous media is still not well understood, and consequently a trial and error approach is usually needed to find the best medium, enzymes and conditions. The goal of this study is to elucidate the mechanism by which organic solvents influence enzymatic stereoselectivity, activity and stability, and thereby enable the rational design of stereoselective systems using the physicochemical properties of the substrate and solvents, together with the enzyme structure. We propose to use a combination of experimental and theoretical methods (enzyme kinetics, sophisticated molecular-modeling and NMR methods) to understand the role of the medium in shaping a biocatalyst structure, activity and stereoselectivity.