HEME PROTEINS AND THEIR SYNTHETIC ANALOGS

本研究的目标涉及综合和 各种血红素蛋白的合成类似物的表征。 的 感兴趣的反应包括（1）配体与血红素结合，（2）氧 金属卟啉的活化和烃氧化，以及（3） 卟啉作为氧化还原伙伴在有组织的媒体之间的相互作用。 这些酶与心血管功能有关;对于药物， 激素和外来生物代谢;氧化剂解毒和 基质氧化;以及生物电子转移， 光合作用 这些研究旨在了解 这些蛋白质反应的分子机制密切相关 模型金属卟啉和寡肽-血红素络合物。 建议的工作包括寡肽-血红素复合物的合成， 全合成血红素蛋白;分子识别的进一步研究 以及基于形状、极性、电荷和 氢键;化学、光化学和光催化生成 高度氧化的铁卟啉络合物;和合成 双卟啉金属配合物。 系统地研究了 氨基酸残基侧翼的配位组氨酸已经揭示了 寡肽疏水相互作用实质性影响 与血红素结合：非极性α-螺旋形成残基增加结合 近105 在合成金属卟啉的研究中， 发展超结构的大循环，如形状，大小和极性 选择性氧化催化剂 我们的“双口袋”卟啉提供 在大环的两面上的空间或极性口袋， 稳定的Fe-O2络合物，并防止氧化降解。 的 空间保护的袋可以诱导形状选择性氧化， 催化末端羟基化和环氧化。 我们的探索 金属卟啉的光化学研究为研究 形成金属-氧代络合物。 利用这一发现可能 允许观察血红素单加氧酶的中间体。 我们在这些领域继续努力， 了解调节蛋白质中配体结合的影响 环境，以进一步表征和分离高氧化 阐述血红素蛋白中间体，以更深入地了解底物 单加氧酶的选择性和区域特异性， 关于卡帕重叠系统中相互作用的知识，例如 光合反应中心 最后，将探讨蛋白质微胶囊的使用。 含半胱氨酸的蛋白质（例如，血清 白蛋白和血红蛋白）产生微米大小的球体， 气体填充的或非水性液体填充的。 蛋白质的发展 微球作为人工红细胞用于O2转运，作为对照 用于磁共振成像的试剂，以及作为自旋标记探针， 体内氧气和温度分析正在进行中。

The objectives of this research involve the synthesis and characterization of synthetic analogs of various heme proteins. The reactions of interest include (1) ligand binding to the heme, (2) oxygen activation and hydrocarbon oxidation by metalloporphyrins, and (3) the interactions between porphyrins as redox partners in organized media. These enzymes are relevant to cardiovascular functioning; to drug, hormone, and exobiotic metabolism; to oxidant detoxification and substrate oxidation; and to biological electron transfer and photosynthesis. These studies are directed towards an understanding of the molecular mechanisms of these protein reactions in closely related model metalloporphyrins and oligopeptide-heme complexes. Proposed work includes the synthesis of oligopeptide-heme complexes as totally synthetic heme proteins; further studies of molecular recognition and substrate specificity on the basis of shape, polarity, charge and hydrogen bonding; chemical, photochemical, and photocatalytic generation of highly oxidized iron porphyrin complexes; and the synthesis of bis(porphyrin) metal complexes. A systematic examination of the effects of amino acid residues flanking a coordinating histidine have revealed the substantial effect of hydrophobic interactions in oligopeptide binding to heme: non-polar alpha-helix forming residues increase binding by nearly 105. In work with synthetic metalloporphyrins, we are developing superstructured macrocycles as shape, size, and polarity selective oxidation catalysts. Our "bis-pocket" porphyrins provide steric or polar pockets on both faces of the macrocycle, produce very stable Fe-O2 complexes, and prevent oxidative degradation. The sterically-protected pockets can induce shape selective oxidations and catalyze terminal hydroxylation and epoxidation. Our exploration of the photochemistry of metalloporphyrins has created a new route to the formation of metal-oxo complexes. Exploitation of this discovery may permit observation of intermediates of heme monooxygenases. Continuation of our efforts in these areas should lead to a quantitative understanding of the influences which modulate ligand binding in protein environments, to further characterization and isolation of high oxidation state heme protein intermediates, to a closer understanding of substrate selectivity and regiospecificity by monooxygenases, and to basic knowledge about the interactions in kappa-overlapping systems such as the photosynthetic reaction center. Finally, the use of protein microencapsulation will be explored. Ultrasonic irradiation of cysteine-containing proteins (e.g., serum albumin and hemoglobin) creates micron-sized spheres that can be either gas-filled or non-aqueous liquid-filled. Development of proteinaceous microspheres as artificial erythrocytes for O2 transport, as contrast agents for magnetic resonance imaging, and as spin-label probes for in vivo O2 and temperature profiling is in progress.