重庆大学生物有机化学_第五章 酶模型

环状冠醚－王冠醚（crown ether）能和金 属阳离子和1º氨基阳离子形成稳定的复合物。
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• The abbreviated nomenclature used is simple；the first number represents the total number of atoms in the ring and the second the total number of heteroatoms.
采用合理的酶模型，可能在忽略不考虑的因素的 情况下，评估每种催化因子的相对重要性。
• That is, with the tools of synthetic chemistry, it becomes possible to construct a “miniature enzyme微型酶” which lacks a macromolecular peptide backbone, but contains reactive chemical groups correctly presented in the geometry dictated by an enzyme active site. It is often referred to as the biomimetic chemical approach to biological systems.
为此，需要知道许多有关于特殊酶行为的机理，包括：活性中 心的结果和酶-底物复合物，酶的特异性及其与底物的结合能 力，酶催化各步的反应动力学和反应过程的中间体。
• Enzymes are complicated molecules and only a few mechanism have been definitively established. This is one of the reasons why model systems are necessary. Among the functional groups found to polypeptide chain those generaily involved in catalytic processes are the imidazole ring, aliphatic and aromatic hydroxyl groups, carboxyl groups, sulphydryl groups, and amino groups.
• The structure of the model should be rigid and well-defined, particularly with respect to substrate orientation and stereochemistry.
模型的结构应是刚性的且确定的，特别是有 关于底物的定向和立体化学方面。
简单有限的几种功能基团是如何参与了催化了大量已知 的酶反应的?酶反应的速率如何解释机理?
• These are the fundamental questions that should be asked during the planning of a bioorganic model of an enzyme.
一个酶模型需要代表多于一种酶的一般特征， 从不同角度看，设计好的酶模型的准则总 结如下：
• Because noncovalent interactions are the key to biological flexibility and specificity, the model should provide a good (hydrophobic) binding site for the substrate.
在设计生物有机化学酶模型中必须要问到的基本问题
• In general, an enzyme model should fulfill a twofold purpose (a) it should provide a reasonable simulation of the enzyme mechanism （需要合理模拟酶反应机理） and (b) it should lead to an explanation of the observed rate enhancement in terms of structure and mechanism（需要从结构和机理角度解释观察到的速度增加 效应）。
Host-Guest Complexation Chemistry 主－客体络合物化学
概述
• 主－客体化学也称主－宾化学（Host-Guest Chemistry）
冠醚
• Crown ethers have the unique ability to form stable complexes with metal ions and primary alkyl ammonium cations.
酶是很复杂的分子，目前仅建立了非常少的酶反 应机理。这就是需要酶模型的原因。常见的催化 基团：咪唑环，脂肪族和芳香族羟基，羧基，巯 基和氨基
• How can such a limited number of functional groups participate in the large variety of known enzymatic reactions and how can the rate of the enzymatic reactions be accounted for in mechanistic terms?
为了将生物有机模型与实际的自然体系关联起来，通过酶模型 得到的所有信息必须最终与在体的酶系统比较并延伸其中
• A model can represent general features for more than one enzyme. Viewed from a different angle, the requirements necessary for the design of a good enzyme model can be summarized in these five criteria:
采用合成化学的方法可能构建也就是经常提到的对生物体系的仿生化学方法
• Therefore, biomimetic chemistry represents the field which attempts to imitate the acceleration and selectivities characteristic of enzymecatalyzed reactions. It is hoped that such an approach will eventually bridge or at least reduce the gap between the known complex structures of organic biomolecules and their exact functions in life.
由于非共价相互作用是生物挠性和专一性的 关键因素，因此模型应为底物提供一个良 好的疏水的结合部位。
• The model should provide the possibility of forming electrostatic and hydrogen bonds to help the substrate bind in the proper way.
• Of course all the informations obtained with enzyme models must ultimately be compared and extended to the in vivo enzymatic system under study in order to correlate the bioorganic models to the real natural system.
• 酶模型是包含一种或多种酶体系特征的有机合成 分子（如仅包含酶活性中心的化学基团与能容纳 底物的具有正确方位和几何构型的“阵容”或催 化洞穴“），比酶小，结构更简单。
• To dissect out a particular factor responsible for the catalytic efficiency of the enzyme within the biological system would be a tremendous task requiring a knowledge of each of the components that would contribute to the overall catalysis.
想要找出对生物体内酶催. 化效率起贡献的特定因 素是一件非常困难的事情，因为这要求了解对总 的催化反应起贡献的所有因素。
• Instead, with appropriate models, it is possible to estimate the relative importance of each catalytic parameter in absence of those not under consideration.
因此仿生化学代表了一个尝试模拟酶催化反应的 加速和选择特征的领域。希望这种方法能最终在 了解有机生物分子的复杂结构和它们的生命功能 之间构架起一个桥梁，或减小它们间的距离。
• In order to do this, many factors related to the mechanism of action of a particular enzyme must be known. These include (a) the structure of the active site and the enzyme-substrate complex; (b) the specificity of the enzyme and its ability to bind to the substrate; and (c) the kinetics for the various steps and a knowledge of possible intermediates in the reaction coordinate.
• The model should preferably be water-soluble, and catalytically active under physiological conditions of pH and temperature.
模型应具备良好的水溶性，而且在生理（pH和温 度）条件下保持催化活性。
生物有机化学 第五章 酶模型
酶模型简介
• Enzyme model are generally organic synthetic molecules that contain one or more features present in enzymatic systems. They are smaller and structrally simpler than enzymes.
模型应提供形成电价键和氢键的可能性，以 利于它同底物以适当的方式结合。
• Carefully selected catalytic groups have to be properly attached to the model to effect the reaction.
精心挑选的催化基团，应恰当地配置在模型 上，促使反应的发生。