Conformational Flexibility and Halogen Bonding in Thyroid Hormones and Their Metabolites

Mondal, Santanu; Mugesh, Govindasamy

doi:10.1021/acs.cgd.6b00945

Cited by 14 publications

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“…A mechanism for T4 deiodination by naphthyl‐based deiodinase mimics was proposed involving the formation of halogen bonding (XB) between chalcogen and iodine atoms . Both experimental results and theoretical investigations demonstrated that the formation of a halogen bond between chalcogen and iodine atoms is crucial for the biomimetic deiodination to occur . Very recently, the Mugesh's group proved that the tellurol containing species, ( 4 and 5 in Scheme ), show a considerably increased deiodination rate .…”

Section: Introductionmentioning

confidence: 99%

The role of the halogen bond in iodothyronine deiodinase: Dependence on chalcogen substitution in naphthyl‐based mimetics

et al. 2019

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The effects on the activity of thyroxine (T4) due to the chalcogen replacement in a series of peri-substituted naphthalenes mimicking the catalytic function of deiodinase enzymes are computationally examined using density functional theory. In particular, T4 inner-ring deiodination pathways assisted by naphthyl-based models bearing two tellurols and a tellurolthiol pair in peri-position are explored and compared with the analogous energy profiles for the naphthalene mimic having two selenols. The presence of a halogen bond (XB) in the intermediate formed in the first step and involved in the rate-determining step of the reaction is assumed to facilitate the process increasing the rate of the reaction. The ratedetermining step calculated energy barrier heights allow rationalizing the experimentally observed superior catalytic activity of tellurium containing mimics. Charge displacement analysis is used to ascertain the presence and the role of the electron density charge transfer occurring in the ratedetermining step of the reaction, suggesting the incipient formation or presence of a XB interaction.

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Section: Introductionmentioning

confidence: 99%

The role of the halogen bond in iodothyronine deiodinase: Dependence on chalcogen substitution in naphthyl‐based mimetics

et al. 2019

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“…However, the binding of THs to DIOs in different conformations is yet to be experimentally verified. [52,53]…”

Section: Metabolism Of Thyroid Hormonesmentioning

confidence: 99%

Chemical Biology of Thyroid Hormones

2023

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March 2023 | 137 thyroid gland to make thyroid hormones (THs). Upon reaching an optimum concentration in the blood plasma, the secretion of T4 from the thyroid gland is stopped by a negative feedback mechanism. [3,4] THs regulate different physiological functions of the human body like cardiovascular function, normal growth, and maturation of bones and overall metabolism of fat, protein, and carbohydrate. They also control the body temperature, heart rate and protein synthesis. This general article highlights the basic chemistry associated with THs synthesis, transport, and metabolism (Figure 1). Biosynthesis of thyroid hormonesThe biosynthesis of THs takes place in the colloidal lumen of thyroid follicular cells with the help of thyroglobulin (Tg, a highly crosslinked glycoprotein), thyroid peroxidase (TPO), iodide (I-), and hydrogen peroxide albumin (HSA). T4 then enters the target cells through membrane-associated transporters like monocarboxylate transporter 8 (MCT8),10 (MCT10) and organic anion transporter 1c1 (OATP1C1). Subsequently, T4 undergoes monodeiodination by iodothyronine deiodinase (DIOs) enzymes to produce the active form of thyroid hormone T3, which further binds with the thyroid nuclear receptors and recognizes different thyroid hormone-responsive elements (TREs) of target genes and regulates the gene translation. The secretion of THs by thyroid are controlled by hypothalamus and pituitary. Hypothalamus secretes thyrotropin-releasing hormone (TRH), a tripeptide (pyro glutamyl-histidyl-proline amide), which stimulates the pituitary to synthesize and release the thyroid-stimulating hormone (TSH) which signals the

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Halogen Bonding Increases the Potency and Isozyme Selectivity of Protein Arginine Deiminase 1 Inhibitors

et al. 2019

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Conformational Flexibility and Halogen Bonding in Thyroid Hormones and Their Metabolites

Cited by 14 publications

References 76 publications

The role of the halogen bond in iodothyronine deiodinase: Dependence on chalcogen substitution in naphthyl‐based mimetics

The role of the halogen bond in iodothyronine deiodinase: Dependence on chalcogen substitution in naphthyl‐based mimetics

Chemical Biology of Thyroid Hormones

Halogen Bonding Increases the Potency and Isozyme Selectivity of Protein Arginine Deiminase 1 Inhibitors

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