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Molecular Design of Artificial Oxygen Carrier Utilizing Myoglobin

利用肌红蛋白的人工氧载体的分子设计

基本信息

批准号：
18590094
负责人：
NEYA Saburo
金额：
$ 2.52万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Sufficient blood supply in medical service and disaster occasion is important. In the present research, we attempted the functional conversion of myoglobin, a biological oxygen reservoir to serve it as a novel oxygen carrier. Since myoglobin is a monomer while hemoglobin is tetrameric, the application of myoglobin as a artificial oxygen carrier could enhance the stability of the the products. We synthesized a new porphyrin isomer corrphycene and the iron complex. The iron corrphycene was coupled with apomyoglobin to create the semi-artificial myoglobin with the lowered oxygen affinity and increased oxygen carrying ability. The artificial prosthetic was found to be successfully incorporated into the protein pocket of apomyoglobin to afford the reconstituted protein as evidenced from several spectroscopic evidence. The oxygen affinity of the myoglobin was found to be P_50 = 6.7 mmHg, corresponding to a 1/10 oxygen affinity as compared with that of native myoglobin. The observation demons … More trates that the oxygen transport ability of the new myoglobin is 8 times larger than native myoglobin. When we introduced two ethoxycarbonyl (-CO_2C_2H_5) substituents into the corrphycene molecule, the oxygen transport ability of the myoglobin with P_50 = 37 mmHg was further increased to 21-fold. These observations demonstrate that myoglobin was successfully converted from oxygen storage molecules into an efficient oxygen carrier like hemoglobin. It is now evident that myoglobin is a promising candidate to develop the artificial oxygen carrier. When the ethoxycarbonyl substituents were attached to the bipyrrole moiety in corrphycene, the P_50 value of the reconstituted myoglobin decreased down to 300 mmHg. The result indicates that the oxygen transport of the third myoglobin became worse owing to the significant decrease oxygen affinity. The above observations, taken together, indicate that the oxygen affinity of myoglobin was be efficiently controlled with the alteration of the structure of the heme macrocycle and the introduction of the electron-withdrawing substituents. The present research provides the first concrete evidence to construct the artificial oxygen carrier based on myoglobin. Less

充足的血液供应在医疗服务和灾难情况下非常重要。在本研究中，我们尝试对肌红蛋白（一种生物氧储库）进行功能转换，使其成为新型氧载体。由于肌红蛋白是单体，而血红蛋白是四聚体，因此应用肌红蛋白作为人工氧载体可以增强产品的稳定性。我们合成了一种新的卟啉异构体corrphycene和铁络合物。铁烯与脱辅基肌红蛋白偶联产生了氧亲和力降低、携氧能力增强的半人工肌红蛋白。多个光谱证据证明，人工假体已成功融入脱肌红蛋白的蛋白质袋中，以提供重构的蛋白质。发现肌红蛋白的氧亲和力为P_50 = 6.7 mmHg，相当于天然肌红蛋白的氧亲和力的1/10。观察表明，新肌红蛋白的氧运输能力比天然肌红蛋白大8倍。当我们在corrphycene分子中引入两个乙氧基羰基（-CO_2C_2H_5）取代基时，P_50 = 37 mmHg的肌红蛋白的氧运输能力进一步提高至21倍。这些观察结果表明，肌红蛋白成功地从储氧分子转化为血红蛋白等有效的氧载体。现在很明显，肌红蛋白是开发人造氧载体的有希望的候选者。当乙氧基羰基取代基连接到corrphycene中的联吡咯部分时，重构的肌红蛋白的P_50值下降至300mmHg。结果表明，由于氧亲和力显着降低，第三肌红蛋白的氧运输变得更差。上述观察结果表明，通过改变血红素大环结构和引入吸电子取代基，可以有效地控制肌红蛋白的氧亲和力。本研究为构建基于肌红蛋白的人工氧载体提供了第一个具体证据。较少的