TRIPOD LIGANDS FOR ENZYME MODELS AND ANION COMPLEXATION

用于酶模型和阴离子络合的三脚架配体

• 批准号: 3305943
• 负责人: GERARD PARKIN
• 金额: $ 20.14万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3305943
• 关键词: X ray crystallography; active sites; anions; carbonate dehydratase; chemical structure function; chemical synthesis; enzyme model; enzyme substrate complex; ligands; metalloenzyme; nuclear magnetic resonance spectroscopy; receptor binding; stereochemistry; thermodynamics

The role of coordination chemistry in biological systems, ranging from the traditional coordination chemistry of cations, to the host-guest chemistry of anions and neutral molecules, can not be understated. Important examples of coordination and host-guest chemistry in biological systems can be observed in the catalytic properties associated with metal ions in metalloenzymes, the base-pairing of nucleic acids, and the interaction of enzymes with substrates. In view of the complexity of biological systems, studies on smaller synthetic model systems may be used to provide key information in order to elucidate many fundamental biological processes. The thrust of this proposal is to develop some new model systems that will generate important information regarding the roles of both cationic and anionic species in biological systems. Specific goals include (i) introduction of a modified ligand systems for establishing well-defined structural and chemical models for carbonic anhydrase, an important enzyme with respect to aspects of respiration and intracellular CO2/HCO3- equilibration, and (ii) the synthesis and applications of series of new low-coordinate tripodal receptor systems that are designed to bind strongly, but to only one face of an anionic substrate. The aims of this research will be achieved by a combination of solution and solid-state studies. Single crystal X-ray diffraction will be used to determine coordination environments of the metalloenzyme models and also the detailed nature of the host-guest interaction in the solid state. 1H, 13C and 17O NMR spectroscopy will provide further characterization of the metalloenzyme models and also a means for measuring kinetic and thermodynamic parameters. A variety of spectroscopic techniques (e.g. 35C1 NMR spectroscopy) will be used to determine association constants and the strength of the host-guest interaction. Standard chemical techniques will be utilized to investigate applications of these receptor systems in areas such as chiral resolution and phase transfer catalysis.

配位化学在生物体系中的作用，包括 传统的阳离子配位化学， 化学的阴离子和中性分子，不能低估。 生物化学中的配位和主客体化学的重要例子 系统中可以观察到与金属相关的催化性能 金属酶中的离子，核酸的碱基配对， 酶与底物的相互作用。 是在复杂的 生物系统，对较小的合成模型系统的研究可能是 用于提供关键信息，以阐明许多基本的 生物过程。 这项建议的主旨是发展一些新的 模型系统，将产生重要的信息， 阳离子和阴离子物种在生物系统中的作用。 具体目标包括（i）引入修饰的配体系统， 建立碳的结构和化学模型 脱水酶，一种在呼吸和呼吸方面重要的酶 细胞内CO2/HCO 3平衡，和（ii）合成和 系列新型低配位三脚架受体系统的应用 它们被设计成强烈地结合，但只结合阴离子表面的一面， 衬底 本研究的目的将通过结合 溶液和固态研究。 单晶x射线衍射 将用于确定金属酶的配位环境 模型，也是主客互动的详细性质， 固体状态。 1H、13 C和17 O NMR光谱将进一步提供 表征的金属酶模型，也是一种手段， 测量动力学和热力学参数。 各种 光谱技术（例如35 C1 NMR光谱）将用于 确定缔合常数和主客体的强度 互动 将使用标准化学技术， 研究这些受体系统在以下领域的应用， 手性拆分和相转移催化。