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: 2178291
• 负责人: MICHELLE M. MILLAR
• 金额: $ 12.44万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 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 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2178291
• 关键词: Mossbauer spectrometry; Raman spectrometry; X ray crystallography; alcohol dehydrogenase; aminothiol; chemical models; chemical structure function; chemical synthesis; cysteine; drug interactions; electron spin resonance spectroscopy; hydrogenase; infrared spectrometry; iron; iron sulfur protein; ligands; mass spectrometry; metalloproteins; molybdenum; nickel; nuclear magnetic resonance spectroscopy; oxidation reduction reaction; oxidoreductase; palladium; platinum; protein structure; rubredoxins; sulfites; thioether; thiols; ultraviolet spectrometry

The research objectives are 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; these proteins are of vast biological and medical significance. The approach is to use sterically encumbered thiolates to create new types of complexes which mimic some of the more unusual properties exhibited by metal-cysteine centers in proteins. The rationale behind this approach comes from the thought that proteins act as sterically hindered ligands. Interestingly, there are numerous examples where monomeric, high-valent metal-cysteine centers are stabilized in proteins under conditions where simple organic thiolates would interact with metals to form low-valent, oligomeric species. Results obtained in our laboratory have demonstrated that sterically encumbered thiolates react with metals: (1) to form monomeric species, and (2) to stabilize metals in high oxidation states. Using this approach, we have prepared synthetic analogs for: (1) the oxidized form of rubredoxin, [Fe(SR)4]1-; (2) the oxidized form of high potential iron-sulfur proteins, [Fe4S4(SR)4]1-; (3) the molybdenum containing oxidases, [O=Mo(VI)(SR)4]; (4) the Ni(III) center in hydrogenases and carbon monoxide dehydrogenase [Ni(SR)4]1-. Additional compounds have been acquired for which there is, as yet, no direct biological analogy: [Fe4S4(SR)4]0, [Ru(SR)4(CO)], [Co(SR)4]1-, etc. We intend to exploit the chemistry of these compounds and to extend this approach to new challenges. Chemico-physical studies of these models compounds will be used to achieve a fundamental understanding of the relationship between the spectroscopic and electronic properties of the metal center. Moreover, the spectroscopic parameters determined for a variety of related metal-thiolate model compounds should be useful to biochemists in their efforts to identify and distinguish different types of metal-cysteine coordination modes. A number of spectroscopic techniques are used to characterize the compounds including: X-ray crystallography, electrochemical, magnetic susceptibility electronic, vibrational, NMR, ESR, MCD, EXAFS, and Mossbauer measurements.

研究目标是合成并充分表征新类型 金属硫醇酸盐络合物的目的 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；这些蛋白质是 具有广泛的生物学和医学意义。 方法是使用 在空间上固定的硫醇酯，以创建新型的复合物 模仿金属半胱氨酸表现出的一些更异常的特性 蛋白质中心。 这种方法背后的理由来自 认为蛋白质是在空间上阻碍的配体。 有趣的是，有许多单体，高价值的例子 在条件下，金属半胱氨酸中心在蛋白质中稳定 简单的有机硫醇酯会与金属相互作用，形成低价值， 寡聚物种。 我们实验室获得的结果已证明 那个固定的硫醇酯与金属反应：（1）形成 单体物种和（2）在高氧化状态下稳定金属。 使用这种方法，我们为：（1） Rubredoxin的氧化形式，[Fe（SR）4] 1-; （2）高的氧化形式 潜在的铁硫蛋白，[Fe4S4（SR）4] 1-; （3）钼 含有氧化酶，[o = mo（vi）（sr）4]; （4）NI（III）中心 氢化酶和一氧化碳脱氢酶[Ni（SR）4] 1-。 额外的 迄今为止尚无直接的化合物 生物学类比：[Fe4S4（SR）4] 0，[RU（SR）4（CO）]，[CO（SR）4] 1-等。我们 打算利用这些化合物的化学反应并扩展 应对新挑战的方法。 这些模型化合物的化学物理研究将用于实现 对光谱镜之间关系的基本理解 金属中心的电子特性。 此外，光谱学 针对各种相关金属 - 硫醇酸盐模型确定的参数 化合物应该对生物化学家识别和 区分不同类型的金属半胱氨酸协调模式。 一个数字 光谱技术用于表征化合物 包括：X射线晶体学，电化学，磁化率 电子，振动，NMR，ESR，MCD，EXAFS和MOSSBAUER测量。