کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
217889 | 463172 | 2016 | 6 صفحه PDF | دانلود رایگان |
• Gold nanoparticle coated chitosan/reduced graphene oxide nanocomposites for cytochrome P450s immobilization.
• The immobilized CYP2D6 and CYP1A1 displayed direct electrochemistry and electrochemically-driven drug metabolism.
• The bioconversion of tramadol or benzo[a]pyrene were achievied by an electrochemistry-driven way.
• The metabolic inbibition of the quinidine and alpha-naphthoflavone to the enzymatic activity of CYP2D6 and CYP1A1 were evaluated.
In the present work, gold nanoparticles coated chitosan/reduced graphene oxide (Au-CS-RG) was prepared for cytochrome P450 2D6 (CYP2D6) and cytochrome P450 1A1 (CYP1A1) immobilization, investigation of the direct electrochemistry and electrochemically-driven drug metabolism. The immobilized CYP2D6 and CYP1A1 displayed respectively a pair of redox peaks with a formal potential of − 492 ± 4 and − 504 ± 6 mV. The response showed a surface-controlled electrode process with an average electron transfer rate constant of 5.19 ± 0.3 s− 1 for CYP2D6 and 3.24 ± 0.4 s− 1 for CYP1A1 determined in the scan rate of 100 mV/s. When the Au-CS-RG was treated with polyacrylic acid (PAA), the resulting nanocomposites (PAA-Au-CS-RG) changed the surface charge of Au-CS-RG from positive to negative and increased the size of the coated gold nanoparticles from ~ 15 to ~ 25 nm. This led to negative-shift of the formal potential to − 513 ± 6 mV for CYP2D6 and − 509 ± 5 mV for CYP1A1, while the electron transfer rate constant decreased to 4.10 ± 0.3 s− 1 for CYP2D6 and 2.78 ± 0.2 s− 1 for CYP1A1, respectively. The immobilized CYP2D6 and CYP1A1 in both cases showed excellent electrochemically-driven drug metabolism. The LC-MS analysis demonstrated the bioconversion from tramadol or benzo[a]pyrene to o-demethyl-tramadol or 7.8-diol benzo[a]pyrene by the electrochemically-driven way, respectively. The metabolic inhibition of the quinidine and alpha-naphthoflavone to the enzymatic activity of CYP2D6 and CYP1A1 were also evaluated.
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Journal: Journal of Electroanalytical Chemistry - Volume 772, 1 July 2016, Pages 46–51