Hormones, peptide antagonists

The identification of distinct functions of the ssts has also been hampered by the lack of high-affinity antagonists. Recently the identification of novel disulfide-linked cyclic octapeptide antagonists of SST was described that contain a core structure of a DL-cysteine pair at positions 2 and 7 of the peptides (Bass et al. 1996). One of these peptide antagonists, [Ac-4-N02-Phe-c(D-Cys-Tyr-D-Trp-Lys-Thr-Cys)-D-Tyr-NH2], displays a binding affinity to SST2 comparable with that observed for the native hormone and reverses SST-mediated inhibition of cAMP in cells transfected with... 

Have you been able to construct peptide antagonists by concentrating on the address region of the hormones i.e. by making compounds which could block the initial interaction of the peptide with the address recognition region of the cell membrane ... 

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). 

For a large number of dmgs, including neurotransmitters, peptide and protein hormones (qv), and thein analogues and antagonists, the ceU membrane is the principal locus of action. Concepts of ceU membrane stmcture are derived from the original Davson-DanieUi Hpid bilayer hypothesis. 

Prolactin is peptide hormone secreted by the pituitary gland. It acts on prolactin receptors in breast tissue where it stimulates production of casein and lactalbu-min. It also acts on the testes and ovaries to inhibit the effects of gonadotrophins. Since the secretion of prolactin is under tonic dopaminergic inhibition by the hypothalamus, dopamine D2-receptor antagonists... 

The luteinizing hormone releasing hormone antagonist RS-26306 (Fig. 6.19) is another example of a peptide analogue that undergoes hydrolysis of its terminal CONH2 group. This decapeptide contains five synthetic amino... 

Numerous other peptides and proteins have been, or are still in development as inhalation products with the objective of systemic absorption. Examples of these are calcitonin, LH-RH antagonists, recombinant human granulocyte colony-stimulating factor and growth hormone. 

---