Molecular design of artifical enzyme systems based on supramolecular effects

1.设计并合成了具有诱导拟合功能的章鱼型环番、通过锁-钥匙机制识别客体分子的笼型环番、介于这些结构类型的主体之间的甾体环番、作为肠杆菌素模型的六环番以及功能化的DNA嵌入剂等人工受体。这些人工受体在水溶液中表现为有效的细胞内受体，反映了个体分子特征。此外，当嵌入由合成肽脂质形成的双层膜中时，这些受体充当有效的细胞表面受体。特别是，手性笼型环番分子嵌入双层膜中，对人工酶的底物疏水氨基酸具有手性识别行为.人工维生素B_6酶均由双层肽脂质、疏水性维生素B_6衍生物和金属离子组成，在温和的水介质中表现出转氨酶、色氨酸合成酶和醛缩酶的催化活性，可介导氨基酸的立体专一性转化.人工维生素B_2<12>酶由疏水性维生素B_2衍生物<12>和双层形成脂质形成，具有甲基丙二酰辅酶A β、谷氨酸β和α-亚甲基戊二酸β的催化功能。通过人工酶与能够活化底物的助催化剂的组合，伴随着碳骨架重排的异构化反应伴随着人工酶的周转而进行。具有转氨酶活性的双层型人工维生素B_6酶和具有谷氨酸脱氢酶活性的双层型人工维生素B_6<12>酶可以相互连接以连续进行各自的反应。

1. The following artificial receptors, which are capable of controlling catalytic activities of artificial enzymes, were designed and synthesized : octopus cyclophanes having the induced-fit function, cage-type cyclophanes being recognizable guest molecules through the lock-and-key mechanism, steroid cyclophanes having intermediate character between these structual types of hosts, hexapus cyclophanes as enterobactin models, and functionalized DNA-intercalators.2. These artificial receptors perform as efficient intracellular receptors in aqueous solutions, reflecting the individual molecular characteristics. In addition, these receptors act as effective cell-surface receptors, when embedded in bilayr membranes formed with synthetic peptide lipids. Especially, a chiral cage-type cyclophane incorporated in a bilayr membrane exhibits chiral recognition behavior toward hydrophobic amino acids, the substrates for artificial enzymes.3. The artificial vitaminB_6enzymes, each constituted with a bilayr-forming peptide lipid, hydrophobic vitaminB_6derivative, and metal ions, show catalytic performance as transaminase, tryptophan synthase, and aldolase under mild conditions in aqueous media to mediate stereospecific transformation of amino acids.4. The artificial vitaminB_<12>enzymes, each formed with a hydrophobic vitaminB_<12>derivative and a bilayr-forming lipid, exhibit catalytic functions as methylmalonyl-CoA mutase, glutamate mutase, and alpha-methyleneglutarate mutase. By combination of the artificial enzyme with a co-catalyst capable of activating the substrates, the isomerization reactions accompanied with the carbon-skeleton rearrangement proceed with turnover of the artificial enzyme.5. A bilayr-type artificial vitaminB_6enzyme having a transaminase activity and a bilayr-type artificial vitaminB_<12>enzyme having a glutamate mutase activity can be interconnected to perform the respective reactions successively.