Thyroxine structural requirements

Further st udy of the effect of various analogs of thyroxine on the swelling of mitochondria in vitro (Shaw el al., 19,59) has revealed that thyronine derivatives la( king a halogen substitution in cither ring of the diphenyl ether have little or no activity there is a similar structural requirement for... 

In search for mimetics ofthe thyroid hormones, more than a hundred analogous compounds were prepared and the structural requirements for thyroxine-like potency investigated in binding studies, e.g. at the rat liver nuclear receptor (Fig. 6.28 and Tab. 6.1). [85]... 

The structure of thyroxine, a thyroid hormone that helps to regulate metabolic rate, was determined in part by comparison with a synthetic compound believed to have the same structure as natural thyroxine. The final step in the laboratory synthesis of thyroxine by Harington and Barger, shown helow, involves an electrophilic aromatic substitution. Draw a detailed mechanism for this step and explain why the iodine substitutions occur ortho to the phenolic hydroxyl and not ortho to the oxygen of the aryl ether. [One reason iodine is required in our diet (e.g., in iodized salt) is for the biosynthesis of thyroxine.]... 

Although radioiodinated antibodies have acceptable stability for in vitro applications, their in vivo stability is less ideal These tracers can act as substrates for the iodotransferase enzymes which are normally responsible for metabo lism of the thyroid hormones thyroxine and tri-iodothyronine which bear structural similarities. Although not present in the vascular circulation, these enzymes are widely distributed in many tissues and their action results in the intracellular release of the radionuclide which then either diffuses or is actively transported out of the cell and subsequently excreted in the urine. In order to try and increase the in vivo stability of antibodies labelled with radioiodine, alternative synthetic strategies have been pursued which result in molecules which are not substrates for the iodotransferases (11. 12). AU of these techniques are more complicated than the electrophilic substitution methods described above and require some synthetic chemistry in order to prepare the precursors which are not commercially available. 

Tetrabromobisphenol A (4,4 -isopropylidenebis(2,6-dibromophenol) TBBPA) is the most widely used BFR in terms of production quantities [2]. It is used as both a reactive and an additive BFR in a variety of polymers, epoxy resins, and adhesives and, in particular, is a constituent in printed circuit boards at levels up to 34% (mass fraction). The acute toxicity of TBBPA is relatively low however, concern for its potential as an endocrine disrupter exists. TBBPA shares structural similarities to thyroxine (T4), and the compoimd competitively binds to the thyroid hormone transport protein transthyretin [135]. Analysis by gas chromatography requires derivitization, and LC methods are preferred to reduce sample processing. Biotransformation of TBBPA... 

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