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

天然酶具有响应于底物、产物或其他效应物的浓度来控制其活性的机制。相反，尽管已经报道了许多具有高催化活性或高底物选择性的成功的人工酶，但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方向是发展化学方法来控制人工酶的活性。本项目构建了具有变构系统等调控系统的新型超分子组装体。1）制备了环糊精二聚体（βCβH），它具有位于两个β-环糊精之间的催化位点，可作为人工水解酶。βCβH具有同调变构样效应。2）利用噻唑基修饰的β-环糊精二聚体合成了用于安息香缩合反应的人工全酶。具有L-天冬氨酸残基作为连接两个β-环糊精单元的接头的二聚体在苯偶姻缩合中引起26倍的加速，而具有L-谷氨酸残基的接头的二聚体仅引起7倍的加速，表明二聚体的接头长度是该人工全酶中的重要因素。3）在伯或仲链上带有苯并冠部分的β-环糊精衍生物，合成了羟基侧，用于对两性离子形式色氨酸（Trp）的分子识别。由于色氨酸的铵离子部分位于环糊精的仲羟基侧，因此仲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.