SYNTHETIC PROBES OF HEME AND CHLOROPHYLL BIOCHEMISTRY

血红素和叶绿素生物化学的合成探针

• 批准号: 3280386
• 负责人: ANDREW D HAMILTON
• 金额: $ 9.92万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1987-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3280386
• 关键词: chemical models; chemical structure function; chlorophyll; cytochrome P450; dimer; enzyme model; heme; photosynthesis; porphyrins

We plan to use the synthetic model approach to probe the mechanisms by which nature controls and modifies the chemistries of the hemes and chlorophylls. We will concentrate on two areas of strong current interest, the photosynthetic reaction centers and cytochrome P-450. A new method is proposed for the preparation of covalently stacked porphyrin derivatives which will serve as accurate models for reaction centers. Using a newly synthesized symmetrical porphyrin precursor we will prepare dimers, trimers and oligomers of varying geometries, compositions and metallation states. Detailed physical and spectroscopic analysis of these molecules will provide insights into the geometrical arrangement of chlorophylls in photosynthesis. We are also proposing to synthesize models of the chlorophyll dimer - pheophytin donor-acceptor complex in order to probe the factors which control forward and reverse electron transfer in the first photosynthetic charge separation step. Our second research theme involves a study of the role of the substrate-binding site and distal protein groups on the active site of the important monooxygenase enzyme, cytochrome P-450. We have prepared a series of molecular receptors which contain a synthetic substrate binding site in close proximity to a porphyrin. These novel species should accurately model the enzyme-substrate complex and allow us to study the molecular mechanism in detail. Various distal groups will be incorporated into the molecular receptor and their influence of heme chemistry will be monitored. The receptors also show considerable promise as catalysts for alkane hydroxylation and alkene epoxidation. The enzyme-like properties of substrate selectivity and reaction regiospecificity should in principle be controlled by careful design of the binding site.

我们计划使用合成模型的方法来探索机制， 自然控制和改变血红素的化学性质， 叶绿素 我们将集中讨论当前人们强烈关注的两个领域， 光合反应中心和细胞色素P-450。 了一种新的方法 建议用于制备共价堆叠的卟啉衍生物 这将作为反应中心的精确模型。 采用了新 合成对称卟啉前体，我们将制备二聚体，三聚体 以及具有不同几何形状、组成和偏位态的低聚物。 这些分子的详细物理和光谱分析将 提供了叶绿素的几何排列的见解， 光合作用 我们还建议综合各种模型， 叶绿素二聚体-脱镁叶绿素供体-受体复合物，以探测 控制第一阶段正向和反向电子转移的因素 光合电荷分离步骤。 我们的第二个研究主题涉及研究的作用， 底物结合位点和活性位点上的远端蛋白质组 重要的单加氧酶，细胞色素P-450。 我们准备了一份 一系列含有合成底物结合的分子受体 位置非常接近卟啉。 这些新物种应该 精确地模拟酶-底物复合物，使我们能够研究 详细的分子机制。 将纳入各种远端组 进入分子受体，它们对血红素化学的影响将 监测。 受体也显示出相当大的希望作为催化剂， 烷烃羟基化和烯烃环氧化。 酶的类酶性质 底物选择性和反应区域特异性原则上应 通过仔细设计结合位点来控制。