Dynamics and Function Relationships of Hydrolases in Organic Solvents

有机溶剂中水解酶的动力学和功能关系

• 批准号: 7288966
• 负责人: GABRIEL Luis BARLETTA
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF PUERTO RICO AT HUMACAO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7288966
• 关键词: Acetonitriles; Acidity; Active Sites; Adopted; Affect; Alcohols; Binding; Biological; Catalysis; Complement; Computer Simulation; Condition; Crown Ethers; Data; Dependence; Enzyme Kinetics; Enzymes; Esters; Fluorescence Spectroscopy; Goals; Grant; Histidine; Hydrolase; Incubated; Kinetics; Link; Measurement; Measures; Methods; Organic solvent product; Outcome; Personal Satisfaction; Plant Roots; Pliability; Preparation; Property; Reaction; Recycling; Reporting; Role; Screening procedure; Shapes; Solvents; Specificity; Spectroscopy, Fourier Transform Infrared; Structure; Substrate Interaction; Subtilisin; Subtilisins; Subtilopeptidase A; System; Techniques; Thinking; Triad Acrylic Resin; aqueous; catalyst; chemical property; design; desire; enzyme activity; enzyme mechanism; enzyme structure; esterase; ionization; molecular modeling; preference; research study; success; tetrahydrofuran

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.

规划生物活性有机分子的合成时日益重要的考虑因素 是手性的引入。实现这一目标的一种方法是使用手性催化剂，例如酶， 它们具有高度对映体/活性和特异性，这一特征有利于目标手性的制备 药理活性化合物。这些生物催化剂的另一个特性对人们具有吸引力 有机化学家认为，它们的性质，如对映选择性、前手性选择性和特异性 由有机溶剂控制（当用作反应介质时）。 Olso，酶很便宜，它们 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 是非水介质中酶催化的机制仍不清楚，并且 因此，通常需要采用反复试验的方法来找到最佳的培养基、酶和条件。 本研究的目的是阐明有机溶剂影响酶促反应的机制。 立体选择性、活性和稳定性，从而能够合理设计立体选择性系统 利用底物和溶剂的物理化学性质以及酶的结构。我们 建议结合使用实验和理论方法（酶动力学、复杂的 分子建模和核磁共振方法）来了解介质在塑造生物催化剂中的作用 结构、活性和立体选择性。