HEME PROTEINS AND THEIR SYNTHETIC ANALOGS

本研究的目标涉及到综合和 各种血红素蛋白的合成类似物的表征。这个 感兴趣的反应包括(1)配体与亚铁血红素结合，(2)氧 金属卟啉的活化和碳氢化合物氧化，以及(3) 在有组织的媒体中作为氧化还原伙伴的卟啉之间的相互作用。 这些酶与心血管功能有关；与药物有关， 激素和外源代谢；氧化解毒和 底物氧化；以及生物电子转移和 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。 建议的工作包括低聚肽-血红素络合物的合成 完全合成的血红素蛋白；分子识别的进一步研究 以及基于形状、极性、电荷和底物的特异性 氢键；化学、光化学和光催化生成 高氧化性铁卟啉络合物的合成 双(卟啉)金属络合物。对影响的系统检查 一个协调组氨酸侧翼的氨基酸残基揭示 寡肽中疏水相互作用的实质效应 与血红素的结合：非极性α-螺旋形成残基增加结合 增加了近105人。在合成金属卟啉方面，我们是 发展超结构大循环，如形状、大小和极性 选择性氧化催化剂。我们的“双口袋”卟啉提供了 大循环两侧的立体或极性口袋，产生非常大的 稳定的Fe-O2络合物，防止氧化降解。这个 立体保护的口袋可以诱导形状选择性氧化和 催化末端羟基化和环氧化。我们对世界的探索 金属卟啉的光化学创造了一条新的途径 金属-氧配合物的形成。利用这一发现可能 允许观察血红素单加氧酶的中间体。 我们在这些领域的持续努力应该导致 对蛋白质中调节配基结合的影响的认识 环境，以进一步表征和分离高度氧化 说明血红素蛋白中间体，以便更深入地了解底物 单加氧酶的选择性和区域特异性，以及对碱性 关于卡帕重叠系统中相互作用的知识，如 光合作用反应中心。 最后，对蛋白质微胶囊的应用进行了探索。 含半胱氨酸蛋白质(如血清)的超声辐照 白蛋白和血红蛋白)产生微米大小的球体，可以是 充气或不含水的充液。蛋白质类的研究进展 作为对比，微球作为人工红细胞用于氧气运输 用于磁共振成像的试剂和用作In的自旋标记探针 活体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.