Construction and Application of Supramolecular Assembles Having Regulation Systems for Their Activities

天然酶具有控制其活性的机制，以响应底物、产物或其他效应物的浓度。相比之下，虽然已经有许多成功的具有高催化活性或高底物选择性的人工酶的报道，但关于具有控制其活性的机制的人工酶的报道并不多。因此，超分子化学领域的一个重要研究领域就是开发控制人工酶活性的化学方法。在本项目中，我们构建了具有调节系统的新的超分子组件，如变构系统。1)我们制备了环糊精二聚体(命名为βCβH)，其催化位置位于两个β-环糊精之间，并作为人工水解酶。βCβH表现出均一的变构效应。2)以β-环糊精二聚体为原料，合成了人工合成安息香缩合全酶。以L-天冬氨酸残基为连接体连接两个β-环糊精单元的二聚体对安息香缩合反应有26倍的加速作用，而以L-谷氨酸残基为连接体的二聚体对安息香缩合反应的促进作用仅为7倍，说明二聚体的连接长度是影响该人工全酶活性的重要因素。3)合成了以两性离子形式对色氨酸进行分子识别的β-环糊精衍生物。由于色氨酸的氨阳离子部分位于环糊精的仲羟基侧，因此二次羟基侧修饰比伯羟基侧修饰更有利于色氨酸的识别。

Natural enzymes have mechanisms to control their activities in response to the concentration of substrates, products or other effectors. In contrast, there have not been many reports of artificial enzymes that have mechanisms to control their activities, although many successful artificial enzymes with high catalytic activity or high substrate selectivity have been reported. Thus, an important area of research in the field of supramolecular chemistry is the development of chemical methods to control the activities of artificial enzymes.In this project, we constructed new supramolecular assembles having regulation systems, such as an allosteric system.1) We prepared cyclodextrin dimer (designated βCβH) that has a catalytic site located between two β-cyclodextrins and acts as an artificial hydrolase. βCβH shows homotropic allosteric-like effect.2) Artificial holoenzymes for benzoin condensation were synthesized using thiazolio-appended β-cyclodextrin dimers. The dimer with an L-aspartic acid residue as a linker for connecting two β-cyclodextrin units caused 26-fold acceleration in the benzoin condensation, whereas the dimer with the linker of a L-glutamic acid residue caused only 7-fold acceleration, indicating that the linker length of the dimer is an important factor in this artificial holoenzyme.3) β-cyclodextrin derivatives bearing a benzo-crown moiety at the primary- or secondary-hydroxy side were synthesized for molecular recognition toward tryptophan (Trp) in zwitterionic form. The secondary-hydroxy side modification was preferable to the primary-hydroxy side one for recognition of Trp, because the ammonium cation part of Trp was located at the secondary-hydroxy side of the cyclodextrin.