HELICAL AND CAVITY MOTIFS ABOUT METAL IONS

关于金属离子的螺旋和空腔图案

• 批准号: 2685029
• 负责人: Andrew S. Borovik
• 金额: $ 8.83万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2685029
• 关键词: active sites; chemical models; free radical oxygen; ions; ligands; metal complex; metalloproteins; protein structure; protein structure function

The aim of this proposed research is to modulate the microenvironments (secondary coordination spheres) about metal ions to direct their chemistry. The approach utilizes the principles of molecular architecture that have been delineated for active sites of metalloproteins. New modular non-heme ligand systems have been designed and synthesized that will address how the structure and morphology of metal binding pockets influence the functional and physical properties of metal complexes. The ligand systems can position functional groups into well-defined arrays to create specific chemical microenvironments. Moreover, weak intraligand and metal-ligand interactions will be employed to orient these arrays relative to the bound metal ions. Once these metal-ligand systems are characterized structurally and physically, they will be used to address how highly reactive oxidized and radical intermediates are regulated in biological systems, to probe structure-function relationships in oxidative catalysis, and understand how metal ions can control the self assembly of helical motifs. Metalloproteins perform chemical reactions that have not yet been achieved in synthetic systems. This chemical versatility follows at least in part from the ability of the proteins to regulate the reactivity of their metal centers by adjustment of their microenvironments. Thus the function and disfunction of biologically-important metalloproteins can be understood in the context of changes in their microenvironments. This type of analysis necessitates basic reactivity studies in which the effects of single components can be analyzed individually as described herein.

这项研究的目的是调节微环境 （二级配位球）关于金属离子以引导其 化学。该方法利用了分子结构的原理 已被描述为金属蛋白的活性位点。新型模块化 非血红素配体系统已被设计和合成，将 解决金属结合袋的结构和形态如何 影响金属配合物的功能和物理性质。这 配体系统可以将官能团定位到明确定义的阵列中 创造特定的化学微环境。此外，弱配体内和 金属-配体相互作用将用于使这些阵列相对定向 到结合的金属离子。一旦这些金属配体系统被表征 在结构和物理上，它们将用于解决如何高度 活性氧化和自由基中间体在生物中受到调节 系统，探索氧化催化中的结构-功能关系， 并了解金属离子如何控制螺旋的自组装 主题。 金属蛋白执行尚未实现的化学反应 在合成系统中。这种化学多功能性至少部分遵循 来自蛋白质调节其金属反应性的能力 通过调整其微环境来调节中心。因此函数和 生物学上重要的金属蛋白的功能障碍可以理解为 他们的微环境变化的背景。这种类型的分析 需要进行基本的反应性研究，其中单一的影响 可以如本文所述单独分析组分。