Peptide thyrotropin

The BZ stmcture also has provided a molecular scaffold for a number of peptide receptor ligands (26). Antagonists for the cholecystokinin (CCK-A) receptor, eg, devazepide (65), the thyrotropin-releasing hormone (TRH) receptor, eg, midazolam (66), and the /i -opiate receptor, eg, tifluadom (67), as well as a series of ras famyl transferase inhibitors, eg, BZA-2B (68) (30) have been identified (Table 4). 

In mammals, peptide hormones typically contain only the a-amino acids of proteins finked by standard peptide bonds. Other peptides may, however, contain nonprotein amino acids, derivatives of the protein amino acids, or amino acids finked by an atypical peptide bond. For example, the amino terminal glutamate of glutathione, which participates in protein folding and in the metabolism of xenobiotics (Chapter 53), is finked to cysteine by a non-a peptide bond (Figure 3—3). The amino terminal glutamate of thyrotropin-... 

Werner, U., T. Kissel, and W. Stuber. Effects of peptide structure on transport properties of seven thyrotropin releasing hormone (TRH) analogues in a human intestinal cell line (Caco-2), Pharm. Res. 1997, 14, 246-250... 

Moss, J., Bundgaard, FI., Prodrugs of peptides 8. In vitro study of intestinal metabolism and penetration of thyrotropin-releasing hormone (TRH) and its prodrugs, Int. J. Pharm. 1990, 66, 39-45. 

PG Pietta, PF Cavallo, K Takahashi, GR Marshall. Preparation and use of benzhydrylamine polymers in peptide synthesis. II. Syntheses of thyrotropin releasing hormone, thyrocalcitonin 26-32, and eledoisin. J Org Chem 39, 44, 1974. 

N-Terminal Glp Ring opening of Glp and cleavage of Glp peptide bonds Luteinizing hormone releasing hormone (Fig. 6.16) Glp-Phe-Leu-Phe-Arg-Pro-Arg, Glp-Leu-Gly-Pro, Glp-His-Pro, and Glp-His Thyrotropin-releasing hormone (Fig. 6.21)... 

K. Ohki, N. Sakura, T. Hashimoto, Hydrolytic Cleavage of Pyroglutamyl-Peptide Bond. IV. Highly Selective Cleavage of Thyrotropin-Releasing Hormone (TRH) in Aqueous Methanesulfonic Acid , Chem. Pharm. Bull. 1997, 45, 194-197. 

H. Bundgaard, J. Mpss, Prodrugs of Peptides. 6. Bioreversible Derivatives of Thyrotropin-Releasing Hormone (TRH) with Increased Lipophilicity and Resistance to Cleavage by the TRH-Specific Serum Enzyme , Pharm. Res. 1990, 7, 885-892. 

S. Muranishi, A. Sakai, K. Yamada, M. Murakami, K. Tanaka, Y. Kiso, Lipophilic Peptides Synthesis of Lauryol Thyrotropin-Releasing Hormone and Its Biological Activity ,... 

Numerically the largest group of signaling substances, these arise by protein biosynthesis (see p. 382). The smallest peptide hormone, thyroliberin (362 Da), is a tripeptide. Proteohormones can reach masses of more than 20 kDa—e.g., thyrotropin (28 kDa). Similarities in the primary structures of many peptide hormones and proteohormones show that they are related to one another. They probably arose from common predecessors in the course of evolution. 

The secretion of anterior pituitary hormones is controlled in part by hypothalamic regulatory factors that are stored in the hypothalamus and are released into the adenohypophyseal portal vasculature. Hypothalamic regulatory factors so far identified are peptides with the exception of dopamine. Secretion of anterior pituitary hormones is also controlled by factors produced more distally that circulate in the blood. Predominant control of hormone production may be relatively simple, as with thyroid-stimulating hormone (TSH), the production of which is primarily stimulated by thyrotropin-releasing hormone (TRH) and inhibited by thyroid hormones, or it may be complex, as with prolactin, the production of which is affected by many neurotransmitters and hormones. 

Various amino acids have been replaced by 4-F-Phe or hexafluorovaline in peptidic hormones oxytocin (4-F-Phe —> lyr), bradykinin (4-F-Phe —> Phe), and angiotensin II. The consequences are diverse, but the stability toward hydrolytic enzymes is generally enhanced. Thus, incorporation of Fs-valine in an octapeptide antagonist of angiotensin II (Sar-AII) notably enhances its in vivo antagonist activity. Analogues of TRH (thyrotropin-releasing hormone), in which histidine is replaced by a fluor-ohistidine (4-F-His and 2-F-His —> His), have better in vivo activities, while the affinities are lower. 

Figure 15 Representative RP-HPLC Separation of the Tryptic/Chymotryptic Peptides of Bovine Thyrotropin p-Subunit bTSHfS Labeled In Situ with the Fluorescent Reagent 5-[(Iodoacetamidoethyl)amino]naphthalene-l-sulfonic acid (5-l-AEDANS) MI a b...

Many small peptides exert their effects at very low concentrations. For example, a number of vertebrate hormones (Chapter 23) are small peptides. These include oxytocin (nine amino acid residues), which is secreted by the posterior pituitary and stimulates uterine contractions bradykinin (nine residues), which inhibits inflammation of tissues and thyrotropin-releasing factor (three residues), which is formed in the hypothalamus and stimulates the release of another hormone, thyrotropin, from the anterior pituitary gland. Some extremely toxic mushroom poisons, such as amanitin, are also small peptides, as are many antibiotics. 

Thyrotropin-releasing hormone (TRH) Vasoactive intestinal peptide Vasopressin Yeast mating factors... 

A pyroglutamyl N terminus is found in the thyrotropin-releasing hormone (Fig. 2-4) and in many other peptide hormones and proteins. It presumably arises by attack of the a-NH2 group of an N-terminal glutamine on the side chain amide group with release of NH3 (Eq. 10-10).111 112... 

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