HEME PROTEINS, MICROSPHERES AND SYNTHETIC ANALOGS

血红素蛋白、微球和合成类似物

• 批准号: 6476722
• 负责人: Kenneth S Suslick
• 金额: $ 32.91万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-12-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6476722
• 关键词: affinity chromatography; analog; biomaterial development /preparation; blood /plasma substitute; catalyst; chemical binding; electrospray ionization mass spectrometry; enzyme activity; fluorescence spectrometry; hemoprotein; intermolecular interaction; laboratory mouse; laboratory rat; magnetic resonance imaging; metalloporphyrins; microcapsule; molecular shape; nuclear magnetic resonance spectroscopy; oxygenases; peptide chemical synthesis; porphyrins; synthetic protein

The objectives of this research involve the characterization and application of heme proteins, heme protein microspheres, and synthetic analogs of heme proteins. The focus is on inter-molecular interactions in three areas: (1) molecular recognition in ligation, sensing and catalysis; (2) porphyrin assemblies, both as covalently linked and as molecular engineered solids, and (3) heme protein assemblies, specifically protein microspheres prepared sonochemically. The chemical reactivities of interest include ligand and peptide binding to heme proteins and metalloporphyrins, oxygen activation and hydrocarbon oxidation by metalloporphyrins, and the interactions between porphyrins as redox partners in organized media. The heme proteins are relevant to cardiovascular functioning; to drug, hormone, and exobiotic metabolism; to oxidant detoxification and substrate oxidation; and to biological electron transfer and photosynthesis. Some of this research provides a fundamental understanding of the molecular mechanisms of heme protein reactivity, using closely related model metalloporphyrins and peptide-heme complexes acting as synthetic heme proteins. The group is exploring molecular recognition and substrate specificity, the nature of heme-peptide and heme-heme interactions, and the chemical and photochemical generation of highly oxidized iron porphyrin complexes. In related work, it has been discovered that ultrasonic irradiation of various proteins (e.g., hemoglobin and serum albumin) creates micron-sized spheres. These microspheres have a very thin shell of crosslinked protein with either a gas- or liquid-filled core. These have been used with substantial success as biocompatible medical diagnostic imaging agents, e.g., as functional magnetic resonance imaging spin-label probes for in vivo O2 and temperature profiling. Microspheres made of Hb and of other proteins are currently under development and animal testing as O2 carrying pharmaceuticals. Continuation of efforts in these areas should lead to (1) the development of a new class of biocompatible microencapsulation for drug and O2 delivery and diagnostic imaging, (2) a quantitative understanding of the influences which modulate ligand binding in protein environments, (3) further characterization of the reactivity of high-oxidation state heme protein intermediates (4) a closer understanding of substrate selectivity and regiospecificity by monooxygenases, and (5) basic knowledge about porphyrin-porphyrin interactions in pi-overlapping systems such as the photosynthetic reaction center.

这项研究的目标包括表征和 血红素蛋白、血红素蛋白微球和合成类似物的应用 血红素蛋白。重点是三个领域的分子间相互作用： (1) 连接、传感和催化中的分子识别； (2) 卟啉 组装体，无论是共价连接还是分子工程固体，以及 (3) 血红素蛋白组装体，具体为蛋白微球的制备 声化学地。感兴趣的化学反应包括配体和 肽与血红素蛋白和金属卟啉结合，氧活化和 金属卟啉对烃的氧化，以及之间的相互作用 卟啉作为有组织介质中的氧化还原伙伴。血红素蛋白是相关的 心血管功能；药物、激素和外生代谢；到 氧化剂解毒和底物氧化；以及生物电子 转移和光合作用。 其中一些研究提供了对分子的基本理解 血红素蛋白反应机制，使用密切相关的模型 金属卟啉和肽-血红素复合物充当合成血红素蛋白。 该小组正在探索分子识别和底物特异性， 血红素-肽和血红素-血红素相互作用的性质，以及化学和 光化学生成高度氧化的铁卟啉配合物。在 相关工作发现，超声波照射各种 蛋白质（例如血红蛋白和血清白蛋白）形成微米大小的球体。 这些微球有一个非常薄的交联蛋白壳，其中有 充满气体或液体的核心。这些已被使用并取得了巨大成功 生物相容性医学诊断成像剂，例如功能性磁性 用于体内 O2 和温度分析的共振成像自旋标记探针。 由 Hb 和其他蛋白质制成的微球目前正在开发中 以及作为 O2 携带药物的动物测试。 在这些领域的持续努力应导致 (1) 发展 用于药物和 O2 输送的新型生物相容性微胶囊 诊断成像，（2）定量理解其影响 调节蛋白质环境中的配体结合，(3) 进一步表征 高氧化态血红素蛋白中间体的反应性 (4) a 更深入地了解底物选择性和区域特异性 单加氧酶，以及（5）有关卟啉-卟啉相互作用的基础知识 在 pi 重叠系统中，例如光合作用反应中心。