A Supramolecular Coordination Cluster as a Functional Monoterpene Synthase Mimic.

作为功​​能性单萜合酶模拟物的超分子配位簇。

• 批准号: 7540725
• 负责人: Jason Michael Nichols
• 金额: $ 4.48万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7540725
• 关键词: Binding; Biological Factors; Biomimetics; Catalysis; Charge; Class; Complex; Computer Systems Development; Cyclization; DNA Sequence Rearrangement; Diphosphates; Electrostatics; Encapsulated; Environment; Enzymatic Biochemistry; Enzymes; Family; Ions; Isoprene; Knowledge; Left; Modeling; Molecular Conformation; Monoterpenes; Organic Synthesis; Process; Public Health; Reaction; Scheme; Shapes; Site; Skeleton; Subgroup; System; Terpenes; Vertebral column; Water; biochemical model; concept; design; diene; geraniol, (Z)-isomer; insight; ionization; limonene synthase; linalool; monoterpene synthase; prevent; size; small molecule; synthetic enzyme; terpene synthase; tool

DESCRIPTION (provided by applicant): Terpene synthases catalyze cascading 1,5-diene, or isoprene, cyclizations to create the carbocyclic backbone of terpene natural products. These enzymes promote cyclization by controlling the conformation and local electrostatic environment of a carbenium ion. The monoterpene synthases catalyze the simplest isoprene cyclizations to form the monoterpenoid class of natural products in which limonene synthase catalyzes the formation of the p-menthane subgroup from geranyl diphosphate. The negatively charged, water-soluble, tetrahedral coordination complexes of the Raymond group are proposed as a limonene synthase mimic that will catalyze the cyclization of geranyl diphosphate derivatives to p-menthane monoterpenoids. Development of the system will provide a relatively simple model for the intracavity environment of limonene synthase and yield a physical description of the interaction between the substrate and cavity, The coordination cage complexes have catalyzed transformations that required either conformational or environmental control over encapsulated intermediates. Therefore, the complexes are proposed to catalyze a biomimetic isoprene cyclization that requires both aspects of reaction control. Specifically, the tetrahedral coordination complex will catalyze the cyclization of nerol or linalool derived substrates as surrogates for geranyl diphosphate. Catalysis should occur within the negatively-charged cavity of the complex driven by hydrophobic encapsulation. Binding will organize substrate conformation, while the negatively charged cavity stabilizes the cationic cyclization intermediates. Encapsulation of the carbenium ion will inhibit rearrangements to monoterpenoids outside of the p-menthane family. This strategy will provide a proof of principle for controlling a carbenium ion by supramolecular encapsulation, serve as the first example of a functional terpene synthase mimic, and probe simple encapsulation as an enzymatic strategy for catalysis. PUBLIC HEALTH RELEVANCE Mimicking enzyme function is an important task for not only validating biochemical models of action, but developing new concepts of small molecule catalysis. A tetrahedral, coordination cage complex is proposed to mimic the function of a class of enzymes known as the monoterpene synthases. Binding of acyclic terpene precursors within the complex's negatively-charged cavity will catalyze their cationic cyclization to the p-menthane family of monoterpenoids in a biomimetic fashion.

描述(申请人提供)：萜烯合成酶催化1，5-二烯或异戊二烯的级联环化反应，以生成萜类天然产物的碳环主链。这些酶通过控制碳正离子的构象和局部静电环境来促进环化。单萜烯合成酶催化最简单的异戊二烯环化反应形成单萜烯类天然产物，其中柠檬烯合成酶催化二磷酸香叶基制得p-薄荷烷亚基。雷蒙德基团的负电荷、水溶性的四面体配位络合物被认为是柠檬烯合成酶的模拟物，它将催化香叶基二磷酸衍生物环化成对薄荷单萜类化合物。该系统的开发将为柠檬烯合成酶的腔内环境提供一个相对简单的模型，并产生底物和腔之间相互作用的物理描述，配位笼络合物催化了需要对被包裹的中间体进行构象或环境控制的转化。因此，这些配合物被认为是催化仿生的异戊二烯环化反应的催化剂，这需要反应控制的两个方面。具体来说，四面体配位络合物将催化橙花醇或芳樟醇衍生的底物作为香叶基二磷酸的替代品的环化反应。催化作用应该发生在疏水包覆驱动的络合物的带负电荷的空腔内。结合使底物构象有序，而带负电荷的空腔稳定阳离子环化中间体。卡宾离子的包裹将抑制对薄荷烷家族以外的单萜类化合物的重排。这一策略将为超分子包埋控制碳正离子提供原理证明，作为第一个模拟功能性萜烯合酶的例子，并探索简单包埋作为一种酶催化策略。与公共健康相关的模拟酶功能不仅是验证生化作用模型的重要任务，也是开发小分子催化的新概念的重要任务。提出了一个四面体的笼状络合物来模拟一类被称为单萜烯合成酶的酶的功能。非环萜类前体在络合物的负电荷空腔内的结合将以仿生的方式催化它们阳离子环化为单萜类化合物的p-薄荷烷家族。