Manna, Debasish and Mondal, Santanu and Mugesh, Govindasamy (2015) Halogen Bonding Controls the Regioselectivity of the Deiodination of Thyroid Hormones and their Sulfate Analogues. In: CHEMISTRY-A EUROPEAN JOURNAL, 21 (6). pp. 2409-2416.
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Abstract
The type1 iodothyronine deiodinase (1D-1) in liver and kidney converts the L-thyroxine (T4), a prohormone, by outer-ring (5) deiodination to biologically active 3,3,5-triiodothyronine (T3) or by inner-ring (5) deiodination to inactive 3,3,5-triiodothronine (rT3). Sulfate conjugation is an important step in the irreversible inactivation of thyroid hormones. While sulfate conjugation of the phenolic hydroxyl group stimulates the 5-deiodination of T4 and T3, it blocks the 5-deiodination of T4. We show that thyroxine sulfate (T4S) undergoes faster deiodination as compared to the parent thyroid hormone T4 by synthetic selenium compounds. It is also shown that ID-3 mimics, which are remarkably selective to the inner-ring deiodination of T4 and T3, changes the selectivity completely when T4S is used as a substrate. From the theoretical investigations, it is observed that the strength of halogen bonding increases upon sulfate conjugation, which leads to a change in the regioselectivity of ID-3 mimics towards the deiodination of T4S. It has been shown that these mimics perform both the 5- and 5-ring deiodinations by an identical mechanism.
Item Type: | Journal Article |
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Publication: | CHEMISTRY-A EUROPEAN JOURNAL |
Publisher: | WILEY-V C H VERLAG GMBH |
Additional Information: | Copy right for this article belongs to the WILEY-V C H VERLAG GMBH, BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY |
Keywords: | enzyme mimics; halogen bonding; iodothyronine deiodinase; sulfate conjugatation; thyroid hormones |
Department/Centre: | Division of Chemical Sciences > Inorganic & Physical Chemistry |
Date Deposited: | 19 Mar 2015 12:06 |
Last Modified: | 19 Mar 2015 12:06 |
URI: | http://eprints.iisc.ac.in/id/eprint/51034 |
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