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HEME PROTEINS, MICROSPHERES AND SYNTHETIC ANALOGS

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
依托单位国家:
美国
项目类别:
财政年份:
1992
资助国家:
美国
项目状态:
已结题
起止时间:
1992-12-01 至 2004-11-30

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中文摘要
翻译
这项研究的目标涉及到表征和 血红素蛋白、血红素蛋白微球及其合成类似物的应用 血红素蛋白的含量。重点放在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 组件,既作为共价连接的,也作为分子工程固体,以及 (3)血红素蛋白组装体,特别是制备的蛋白质微球 用声化学方法。感兴趣的化学反应包括配体和 与血红素蛋白和金属卟啉结合的多肽,氧活化和 金属卟啉对碳氢化合物的氧化及其相互作用 在有组织的媒体中作为氧化还原伙伴的卟啉。这些血红素蛋白是相关的 心血管功能;药物、激素和外来新陈代谢; 氧化剂解毒和底物氧化;以及生物电子 转移和光合作用。 这项研究的一部分提供了对分子的基本理解 用密切相关的模型研究血红素蛋白的反应机理 金属卟啉和多肽-血红素络合物作为合成的血红素蛋白。 该小组正在探索分子识别和底物专一性, 血红素-多肽和血红素-血红素相互作用的性质,以及化学和 高氧化铁-卟啉络合物的光化学生成。在……里面 相关工作中,已发现各种超声波辐照方式 蛋白质(例如,血红蛋白和血清白蛋白)形成微米大小的球体。 这些微球具有一层非常薄的交联蛋白外壳,其中 充气或充液的核心。这些技术已经成功地应用于 生物相容的医学诊断成像剂,例如作为功能磁性的 用于体内氧气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 和动物试验,作为氧气携带药物。 在这些领域的持续努力应导致(1)发展一种 用于药物和氧气输送的新型生物兼容微胶囊和 诊断成像,(2)对以下影响的定量了解 调节蛋白质环境中的配基结合,(3)进一步表征 高氧化态血红素蛋白中间体的反应性(4)a 通过以下方式更深入地了解底物选择性和区域特异性 单加氧酶,以及(5)关于卟啉-卟啉相互作用的基本知识 在圆周率重叠的系统中,如光合作用反应中心。
英文摘要
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.
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