Creation of a Supramolecular CO Receptor for Investigation of Biological Roles of Endogenously-Produced Internal CO

真核生物在血红素氧化酶（HO）降解血红素的过程中不断产生一氧化碳（CO）。由于缺乏内源性CO的敲除方法，CO在生物体中的生物学作用尚未完全了解。我们已经证明，一种超分子复合物hemoCD比血红蛋白更强地结合CO。在本研究中，hemoCD用于去除生物体内的CO，并研究了去除CO后的遗传反应。此外，为了监测人体细胞中CO的耗竭效应，hemoCD支架与一种具有很强的将分子带入细胞内部能力的八精氨酸肽偶联。该偶联物R8-hemoCD被HeLa细胞顺利吸收，无明显毒性。

Carbon monoxide (CO) is continuously produced in the eukaryotic organisms during degradation of hemin by heme oxygenase (HO). The biological roles of CO in the living organisms have not been fully understood because of lacking of knockdown method for endogenously produced CO. We have shown that a supramolecular complex, hemoCD, strongly binds CO higher than that of hemoglobin. In the present study, hemoCD was used for removal of CO in the living organisms and genetic response upon removal of CO was investigated. Furthermore, for monitoring the depletion effect of CO in the human cells, the hemoCD scaffold was conjugated with an octaarginine peptide that has a strong ability to bring molecules into the cell interior. This conjugate, R8-hemoCD, was smoothly taken by the HeLa cells without significant toxicities.