title: Regioselective deiodination of iodothyronamines, endogenous thyroid hormone derivatives, by deiodinase mimics.
abstract: Iodothyronine deiodinases (IDs) are mammalian selenoenzymes that play an important role in the activation and inactivation£ of thyroid hormones. It is known that iodothyronamines (TnAMs), produced by the decarboxylation of thyroid hormones, act as substrates for deiodinases. To understand whether decarboxylation alters the rate and/or regioselectivity of deiodination by using synthetic deiodinase mimics, we studied the deiodination of different iodothyronamines. The triiodo derivative 3,3',5-triiodothyronamine (T3 AM) is deiodinated at the inner ring by naphthyl-based deiodinase mimics, which is similar to the deiodination of 3,3',5-triiodothyronine (T3). However, T3 AM undergoes much slower deiodination than T3. Detailed experimental and theoretical investigations suggest that T3 AM forms a weaker halogen bond with selenium donors than T3. Kinetic studies and single-crystal X-ray structures of T3 and T3 AM reveal that intermolecular I⋅⋅⋅I interactions may play an important role in deiodination. The formation of hydrogen- and halogen-bonding assemblies, which leads to the formation of a dimeric species of T3 in solution, facilitates the interactions between the selenium and iodine atoms. In contrast, T3 AM, which does not have I⋅⋅⋅I interactions, undergoes much slower deiodination.
authors: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012 (India).
authors: Santanu
authors: S
authors: Mondal
authors: Govindasamy
authors: G
authors: Mugesh
mesh_terms: D032701:Biomimetics; D007453:Iodide Peroxidase / Q000737:chemistry*; D008954:Models, Biological; D015394:Molecular Structure; D013237:Stereoisomerism; D013963:Thyroid Hormones / Q000737:chemistry*; D013970:Thyronines / Q000737:chemistry*
chemical_list: C487948:3-iodothyronamine; D013963:Thyroid Hormones; D013970:Thyronines; D007453:Iodide Peroxidase
keywords: enzyme models; hormones; iodine; noncovalent interactions; selenium