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Halogen Bonding Controls the Regioselectivity of the Deiodination of Thyroid Hormones and their Sulfate Analogues

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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Official URL: http://dx.doi.org/ 10.1002/chem.201405442


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
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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