Thyroxine structure

Medium-ring compound synthesis Thyroxin structure and synthesis Vitamin Bj isolation... 

Blake, C.C.F., et al. Structure of human plasma prealbumin at 2.5 A resolution. A preliminary report on the polypeptide chain conformation, quaternary structure and thyroxine binding. J. Mol. Biol. 88 1-12, 1974. 

Thymine, electrostatic potential map of, 1104 structure of, 1101 Thyroxine, biosynthesis of, 551 structure of. 1020 TIme-of-flight (TOP) mass spectrometry, 417-418 Titration curve, alanine, 1023 TMS, see Tetramethylsilane see Trimethylsilyl ether Tollens reagent, 701 Tollens test, 992... 

Bruice TC, Kharasch N, Winzler RJ. A correlation of thyroxine-like activity and chemical structure. Arch Biochem Biophys 1956 62 305-17. 

From the chemical point of view, amiodarone is completely different from other antiar-rhythmics. It has two iodide atoms and a diethylaminoethanol group as substituents in the benzoyl part, and overall it is very similar to the structure of thyroxin-like molecules. 

Figure 8.17. Structure of the iodine-containing amino acid-based thyroid hormones—thyroxine and triiodothyronine...

Thyroxine binding prealbumin (TBPA) carries about 30% T but no Tj. Its affinity is only of the order of 10 M, but it is much more abundant in semm than is TBG. The amino acid sequence and the structure of this protein are known. Four identical subunits (127 amino acids each) form a prolate ellipsoid. Noncovalent interactions between the subunits form a channel of I nm diameter along the long axis, which has a funnel-shaped opening of 2.5 nm. The T molecule is held in one arm of this channel, binding... 

Dronedarone is a structural analog of amiodarone and lacks iodine atoms. The design was intended to eliminate action of the parent drug on thyroxine metabolism and to modify the half-life of the drug. Dronedarone has multiple actions like amiodarone, blocking IKr, IKs, ICa, INa, and adrenoceptors. The drug has a half-life of 24 hours and was administered twice daily in the initial clinical trials. No thyroid or pulmonary toxicity has been noted during early use. 

The structural formulas of thyroxine and triiodothyronine as well as reverse triiodothyronine (rT3) are shown in Figure 38-2. 

This case illustrates the need to verify apparently severe reactions to thyroxine, since such reactions are physiologically unlikely, given that exogenous thyroxine is structurally identical to that produced endogenously. 

The chemical structures of thyroxine and triiodothyronine are shown in Figure 31—1. As shown in the figure, thyroid hormones are synthesized first by adding iodine to residues of the amino acid tyrosine. Addition of one iodine atom creates monoiodotyrosine, and the addition of a second iodine creates diiodotyrosine. Two of these iodinated tyrosines are then combined to complete the thyroid hormone. The combination of a monoiodotyrosine and a diiodotyrosine yields triiodothyronine, and the combination of two diiodoty-rosines yields thyroxine.55... 

FIGURE 31-1 Structure of the thyroid hormones triiodothyronine (T3] and thyroxine (T4X Addition of one iodine atom [I] to tyrosine produces monoiodotyrosine addition of a second iodine atom produces diiodotyrosine. A monoiodotyrosine and diiodotyrosine combine to form triiodothyronine (T3X Coupling of two diiodotyrosines forms thyroxine (T4X... 

The structural formulas of thyroxine and triiodothyronine as well as reverse triiodothyronine (rT3) are shown in Figure 38-2. All of these naturally occurring molecules are levo (L) isomers. The synthetic dextro (D) isomer of thyroxine, dextrothyroxine, has approximately 4% of the biologic activity of the L isomer as evidenced by its lesser ability to suppress TSH secretion and correct hypothyroidism. 

Thyroid hormones and their structural analogs showed lower DPPH-scavenging activity in comparison with butylated hydroxytoluene (BHT) as a standard compound. 3,5,3, 5 -tetraiodothyroacetic acid, 3,3,5 -triiodo-L-thyronine, and thyroxine showed the highest antioxidant activity measured by DPPH reduction, 3,5,3 5 -tetraiodothyroacetic acid having over 20% of the activity of BHT (05). 

In another report, a microchip was interfaced to MS for the detection of the tetrameric plasma protein (transthyretin) which was involved in the transport of thyroxine. Screening of small molecules, including the natural ligand, thyroxine, that could stabilize the tetramer structure was carried out [779]. 

Copper chelates of amino acid enantiomers such as proline or phenylalanine have been used to resolve enantiomers of amino acids and structurally related compounds [241,245]. Other metals such as zinc and cadmium have also been used. Metal chelates have been used to resolve a-amino-a-hydroxy carboxy acids and a-methyl-a-amino acid enantiomers [246]. One example of pharmaceutical interest is the resolution of D-penicillamine from the L-antipod [247] and resolution of L,D-thyroxine [248]. 

A. Wojtczak et al., Structure of rat transthyretin (rTTR) complex with thyroxine at 2.5 A resolution First non-biased insight into thyroxine binding reveals different hormone orientation in two binding sites. Acta. Cryst. D 57, 1061-1070 (2001)... 

Fig. 2. Basic structure of receptors for progesterone (PR), glucocorticoid (GR), oestradiol (ER), thyroxine (T3) and vitamin D (Vit D). The receptors are divided into six domains, A-F [15] and the per-entage homology of region C for each receptor is compared with that for the progesterone receptor [9-14]. The number of amino acids in each receptor is shown on the right-hand side.

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