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Screening of potential substrates or inhibitors of cytochrome P450 17A1 (CYP17A1) by electrochemical methods

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Abstract

The electrochemical redox reactions of the recombinant form of human cytochrome P450 17A1 (CYP17A1) were investigated. The hemoprotein was immobilized on the electrode modified with a biocompatible nanocomposite material based on the membrane-like synthetic surfactant didodecyldimethylammonium bromide (DDAB) and gold nanoparticles. Analytical characteristics of DDAB/Au/CYP17A1 electrodes were investigated using cyclic voltammetry, square wave voltammetry, and differential pulse voltammetry. Analysis of electrochemical behavior of cytochrome P450 17A1 was performed in the presence of a natural substrate, pregnenolone (1), known inhibitor, ketoconazole (2), and in the presence of synthetic derivatives of pregnenolone: acetyl pregnenolone (3), cyclopregnenolone (4), and tetrabromo-pregnenolone (5). Ketoconazole, the azole inhibitor of cytochromes P450, blocked catalytic current in the presence of the substrate, pregnenolone (1). Compounds 3–5 did not demonstrate substrate properties towards the electrode/CYP17A1 system. Compound 3 did not influence catalytic activity with pregnenolone, whereas compounds 4 and 5 demonstrated some inhibitory activity. Thus, electrochemical redox reactions of CYP17A1 may serve as an adequate substitution of the reconstituted system, which requires additional redox partners for manifestation of catalytic activity of hemoproteins of the cytochrome P450 superfamily.

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Authors and Affiliations

  1. Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, ul. Pogodinskaya 10, Moscow, 119121, Russia

    V. V. Shumyantseva, T. V. Bulko, A. Yu. Misharin & A. I. Archakov

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  1. V. V. Shumyantseva
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  2. T. V. Bulko
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  3. A. Yu. Misharin
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  4. A. I. Archakov
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Correspondence to V. V. Shumyantseva.

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Original Russian Text © V.V. Shumyantseva, T.V. Bulko, A.Yu. Misharin, A.I. Archakov, 2011, published in Biomeditsinskaya Khimiya.

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Shumyantseva, V.V., Bulko, T.V., Misharin, A.Y. et al. Screening of potential substrates or inhibitors of cytochrome P450 17A1 (CYP17A1) by electrochemical methods. Biochem. Moscow Suppl. Ser. B 5, 55–59 (2011). https://doi.org/10.1134/S1990750811010124

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  • DOI: https://doi.org/10.1134/S1990750811010124

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