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

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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.