SGER: Bisanthracene-based Mimics of the Hemoglobin Protein

SGER：基于双蒽的血红蛋白模拟物

• 批准号: 0854706
• 负责人: Martin Burke
• 金额: --
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0854706&HistoricalAwards=false
• 关键词: SGER; Bisanthracene; based; Mimics; Hemoglobin

This project aims to synthesize and characterize bis-anthracene-based small molecules with the capacity to mimic the cooperative ligand binding properties of the hemoglobin protein. These properties are critical to its switch-like binding that underlies hemoglobin's respiratory function, enabling rapid saturation with four molecules of oxygen in the lungs and efficient, complete delivery of this cargo to the tissues. This cooperativity is achieved via reciprocated conformational changes at the Fe-heme binding sites mediated via the phenomenon of mechanochemical coupling. A series of bis-anthracene-based small molecules designed to mimic these remarkable properties will be synthesized. These novel compounds will then be systematically evaluated for their capacity to cooperatively bind metal ions or molecular oxygen via mechanochemical coupling using a suite of variable temperature NMR and X-ray crystallographic techniques. The results of these studies will be used to design future derivatives, based on the same bis-anthracene skeleton, with optimized capacity for cooperative oxygen binding.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Martin D. Burke of the Department of Chemistry at the University of Illinois. Professor Burke's research efforts are focused on the synthesis and study of small molecules with the capacity to perform protein-like functions. The synthetic methods developed through this research will have an impact on the preparation of pharmaceuticals, natural products, and materials. The fundamental understanding of the capacity of small molecules to perform higher-order functions will enable the more effective utlilization of such compounds in pharmaceutical applications, including the replacement of missing proteins with "molecular prosthetics."

本项目旨在合成并表征具有模仿血红蛋白配体结合特性的双蒽基小分子。这些特性对血红蛋白的开关式结合至关重要，这种结合是血红蛋白呼吸功能的基础，能够使肺中的四分子氧气快速饱和，并有效、完整地将氧气输送到组织中。这种协同性是通过机械化学偶联现象介导的铁血红素结合位点的往复构象变化来实现的。一系列以双蒽为基础的小分子将被合成来模拟这些显著的性质。然后，这些新化合物将使用一套变温核磁共振和x射线晶体学技术，系统地评估它们通过机械化学偶联结合金属离子或分子氧的能力。这些研究结果将用于设计未来的衍生物，基于相同的双蒽骨架，具有优化的协同氧结合能力。有了这个奖项，有机和大分子化学项目支持伊利诺伊大学化学系Martin D. Burke教授的研究。伯克教授的研究重点是合成和研究具有类似蛋白质功能的小分子。通过本研究开发的合成方法将对药物、天然产物和材料的制备产生影响。对小分子执行高阶功能的能力的基本理解将使这些化合物在制药应用中得到更有效的利用，包括用“分子假肢”替代缺失的蛋白质。