SYNTHETIC ANALOGS FOR METAL-CYSTEINE CONTAINING PROTEINS

含有金属半胱氨酸的蛋白质的合成类似物

• 批准号: 3290021
• 负责人: MICHELLE M. MILLAR
• 金额: $ 8.16万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT ALBANY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1989-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3290021
• 关键词: alcohol dehydrogenase; aspartate carbamoyltransferase; cadmium; chemical models; chemical synthesis; cobalt; copper; cysteine; cytochrome oxidase; drug interactions; iron; metalloproteins; metallothionein; molybdenum; nickel; nitrate reductases; sulfites; thiols; xanthine oxidase; zinc

Our research objective is to synthesize and fully characterize new types of metal-thiolate complexes for the purpose of obtaining fundamental information about the structural, spectroscopic and reactivity properties of proteins containing metal-cysteine interactions. The metal-cysteine ligation mode occurs in a wide range of metalloproteins. Our approach is to use sterically hindered thiolates to create new types of complexes which mimic some to the more unusual properties exhibited by metal-cysteine centers in metalloproteins. The rational leading to this approach is derived from the analogy and the fact that proteins act as sterically bulky ligands. Extensive results obtained in our laboratory have demonstrated that these ligands react with metals: (1) to form monomeric rather than cluster compounds and (2) to stabilize metals in their higher oxidation states. Using this approach, we have prepared synthetic analogs (e.g., [Fe(SR)4]-) for the oxidized form of rubredoxin and synthetic analogs (e.g., [Fe4S4(SR)4]-) for the oxidized form of high potential iron-sulfur proteins. In addition, it is proposed that similar strategies be used to synthesize analogs for proteins containing: iron (iron-sulfur proteins and enzymes); copper (blue copper and cytochrome oxidase); nickel (hydrogenase); and molybdenum (nitrogenase, xanthine oxidase/dehydrogenase, aldehyde oxidase, sulfite oxidase and nitrate reductase). The reactivity properties of these compounds will also be investigated. Chemico-physical studies of these model compounds will be used to achieve a fundamental understanding of the relationship between the spectroscopic and the structural and electronic properties of the metal center. In addition, the spectroscopic parameters determined form a variety of metal-thiolate model compounds whould be useful to biochemists in their efforts to identify and distinguish different types of metal-cysteine coordination modes. A number of spectroscopic techniques will be used to characterize the compounds including: X-ray crystallography, magnetic susceptibility, electrochemical, electronic, vibrational, MCD, NMR, ESR, EXAFS and Mossbauer measurements.

我们的研究目标是合成并充分表征新型 金属硫醇酸盐复合物的目的是获得基本 有关结构，光谱和反应性能的信息 包含金属半胱氨酸相互作用的蛋白质。 金属半胱氨酸 连接模式发生在多种金属蛋白中。 我们的方法是 使用宽带阻碍的硫醇酯创建新型的复合物 模仿金属半胱氨酸所表现出的更异常的特性 金属蛋白中心。 导致这种方法的理性是 源自类比和蛋白质起作用的事实 配体。 我们实验室获得的广泛结果表明 配体与金属反应：（1）形成单体而不是簇 化合物和（2）以稳定较高氧化状态的金属。 使用这种方法，我们准备了合成类似物（例如[Fe（Sr）4] - ） 用于氧化形式的rubredoxin和合成类似物（例如， [Fe4s4（sr）4] - ）对于高电位铁硫的氧化形式 蛋白质。 此外，建议使用类似的策略 合成包含蛋白质的类似物：铁（铁硫蛋白和 酶）;铜（蓝色铜和细胞色素氧化酶）；镍 （氢化酶）;和钼（氮酶，黄嘌呤氧化酶/脱氢酶， 醛氧化酶，亚硫酸盐氧化酶和硝酸盐还原酶）。 反应性 这些化合物的性能也将进行研究。 这些模型化合物的化学物理研究将用于实现 对光谱与光谱之间的关系的基本理解 金属中心的结构和电子特性。 此外， 确定的光谱参数构成了多种金属硫醇酯 模型化合物对生物化学家对他们的努力很有用 识别和区分不同类型的金属半胱氨酸协调 模式。 许多光谱技术将用于表征 这些化合物包括：X射线晶体学，磁化率， 电化学，电子，振动，MCD，NMR，ESR，EXAFS和EXAFS和 Mossbauer测量。