Molecular Design of Artificial Oxygen Carrier Utilizing Myoglobin

在医疗服务和灾难场合，充足的血液供应是重要的。在本研究中，我们尝试了肌红蛋白的功能转化，将其作为一种新型的氧载体。由于肌红蛋白是单体，而血红蛋白是四聚体，因此使用肌红蛋白作为人工氧载体可以提高产物的稳定性。我们合成了一种新的卟啉异构体，并与铁络合物进行了配位。将考拉菲与去肌红蛋白偶联，制得氧亲和力降低、携氧能力增强的半人工肌红蛋白。一些光谱证据表明，该人工假体被成功地结合到无肌红蛋白的蛋白质口袋中，以提供重组蛋白质。肌红蛋白的氧亲和力为P_(50)=6.7 mm Hg，相当于天然肌红蛋白的1/10。观察恶魔…结果表明，新型肌红蛋白的氧转运能力是天然肌红蛋白的8倍。当我们在丙二烯分子中引入两个乙氧羰基(-CO_2C_2H_5)取代基时，肌红蛋白的氧传递能力进一步提高到21倍。这些观察表明，肌红蛋白成功地从储氧分子转化为类似于血红蛋白的有效氧载体。现在很明显，肌红蛋白是开发人工氧载体的一个很有前途的候选者。当丙二烯中的联吡咯部分连接上乙氧羰基取代基时，重组肌红蛋白的P_(50)值降至300毫米汞柱。结果表明，由于氧亲和力的显著降低，第三肌红蛋白的氧转运变差。综上所述，上述观察结果表明，通过改变血红素大环的结构和引入吸电子取代基，肌红蛋白的氧亲和力得到了有效的控制。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的证据。较少

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