Inhibition of peroxidase-catalyzed protein tyrosine nitration by antithyroid drugs and their analogues

Bhabak, Krishna P. ; Mugesh, Govindasamy (2010) Inhibition of peroxidase-catalyzed protein tyrosine nitration by antithyroid drugs and their analogues Inorganica Chimica Acta, 363 (12). pp. 2812-2818. ISSN 0020-1693

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Official URL: http://www.sciencedirect.com/science/article/pii/S...

Related URL: http://dx.doi.org/10.1016/j.ica.2010.03.048

Abstract

In this paper, we describe the effect of some commonly used thiourea-based antithyroid drugs and their analogues on the peroxidase-catalyzed nitration reactions. The nitration of bovine serum albumin (BSA) and cytochrome c was studied using the antibody against 3-nitro-L-tyrosine. This study reveals that the thione-based antithyroid drugs effectively inhibit lactoperoxidase (LPO)-catalyzed nitration of BSA. These compounds show very weak inhibition towards the nitration of cytochrome c. Some of these compounds also inhibit myeloperoxidase (MPO)-catalyzed nitration of L-tyrosine. A structure-activity correlation study on the peroxidase-catalyzed nitration of L-tyrosine reveals that the presence of thione/selone moiety is important for the inhibition. Although the presence of a free N-H group adjacent to C=S moiety is necessary for most of the thiones to inhibit the LPO-catalyzed nitration, the corresponding selones do not require the presence of any free N-H group for their activity. Furthermore, experiments with different concentrations of H2O2 suggest that the antithyroid drugs and related thiones inhibit the nitration reaction mainly by coordinating to the Fe(III)-center of the enzyme active site as previously proposed for the inhibition of peroxidase-catalyzed iodination. On the other hand, the selenium compounds inhibit the nitration by scavenging H2O2 without interacting with the enzyme active site. This assumption is based on the observations that catalase effectively inhibits tyrosine nitration by scavenging H2O2, which is one of the substrates for the nitration. In contrast, superoxide dismutase (SOD) does not alter the nitration reactions, indicating the absence of superoxide radical anion (O2⋅-) during the peroxidase-catalyzed nitration reactions.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Antithyroid Drugs; Protein Nitration; Lactoperoxidase; Bovine Serum Albumin; Cytochrome c; Selenium
ID Code:79302
Deposited On:25 Jan 2012 06:35
Last Modified:25 Jan 2012 06:35

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