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Molecular design of artifical enzyme systems based on supramolecular effects

基于超分子效应的人工酶系统的分子设计

基本信息

批准号：
02102006
负责人：
MURAKAMI Yukito
金额：
$ 131.2万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Specially Promoted Research
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1993
项目状态：
已结题

项目摘要

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.

1.设计并合成了能够控制人工酶催化活性的人工受体：具有诱导匹配功能的章鱼环番结构、笼型环番作为可通过锁和钥匙机制识别的客体分子、具有介于这些结构类型宿主之间的中间性质的类固醇环番、作为肠动蛋白模型的环状六环以及功能化的DNA嵌入体。这些人工受体在水溶液中作为有效的细胞内受体发挥作用，反映了个体的分子特征。此外，这些受体作为有效的细胞表面受体，当被嵌入到由合成多肽脂形成的双层膜中时。尤其是在双层膜中引入的手性笼型环番对人工酶的底物--疏水氨基酸表现出手性识别行为。人工合成的维生素B_6酶由两层形成肽脂、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性能，介导氨基酸的立体特异性转化。人工维生素B_12酶分别由疏水性维生素B_(12)衍生物和形成双层的脂类形成，具有甲基丙二酰辅酶A变位酶、谷氨酸变位酶和α-亚甲基戊二酸变位酶的催化功能。通过将人工酶与能够活化底物的助催化剂相结合，伴随着碳骨架重排的异构化反应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酶和具有谷氨酸变位酶活性的双层型人工维生素B_12酶可以相互连接以依次进行各自的反应。