Journal
ANALYTICAL CHEMISTRY
Volume 85, Issue 21, Pages 9996-9999Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ac402661w
Keywords
-
Categories
Funding
- MEXT, Japan [23350038]
- Grants-in-Aid for Scientific Research [23350038] Funding Source: KAKEN
Ask authors/readers for more resources
The development of a biocatalytic electrode consisting of cytochrome P450 (CYP) proteins would be a key technology with which to establish simple drug metabolizing biosensors or screening devices for drug inhibitors. We have successfully detected the direct electron transfer (DET) from a human CYP layer or a CYP microsome adsorbed on a bare indium tin oxide (ITO) film electrode without any modification layers and applied it to drug metabolism evaluation. We compared the electrocatalytic properties of the two ITO films with different surface nanostructures (polycrystalline or amorphous). CYP on polycrystalline ITO film enhanced the electron transfer rate of oxygen reduction about fifteen times more than with amorphous film. The polycrystalline ITO film was a suitable electrode for the adsorption of CYP proteins while maintaining efficient DET and enzymatic activity, probably because of its larger surface area and negatively charged surface. The oxygen reduction current at the polycrystalline ITO film electrodes had increased 3- to 4-fold, specifically coupled with the oxidation of drugs (testosterone and quinidine) by the monooxygenase activity of CYP. In contrast, the oxygen reduction current completely disappeared in the presence of the CYP inhibitor (ketoconazole). Similar results could be obtained from the CYP microsome with sufficiently clear responses. These results indicate that the CYP modified polycrystalline ITO electrode offers the potential for electrochemically evaluating CYP activity for drug metabolism with a simple configuration.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available