Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various two-dimensional NMR techniques have been used to obtain complete resonance assignments of the protons in the 1-10 fragment of adrenocorticotropic hormone (ACTH). 1H-1H coupling constants among the backbone protons and the chemical shift values measured in aqueous and in dimethyl sulphoxide solutions indicated preference for extended but different conformations in the two solvents.
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PMID:Two-dimensional NMR studies on 1-10 fragment of adrenocorticotropic hormone. 132 81

The most common ectopic production of a pituitary hormone is the one of ACTH leading to Cushing's syndrome. Ectopic ACTH-hypersecretion is the cause of Cushing's syndrome in 10-15% of all cases. The ACTH-secreting tumours are often oat-cell carcinomas of the lung, less frequently pancreatic cancers, hypernephromas, or C-cell carcinomas of the thyroid. Some of these tumours may be benign or semi-benign as the rare carcinoid tumours and cause great problems in the differential diagnosis of ACTH-dependent hypercortisolism. Out of 173 of our patients with Cushing's syndrome observed in the last 12 years 21 were caused by ectopic ACTH-production. Of these 21 patients 13 have a small cell carcinoma of the lung. The ectopic ACTH-syndrome often has typical clinical features caused by the levels of ACTH and cortisol leading to hypocalcemic alkalosis with muscle weakness and wasting, carbohydrate intolerance, and hypertension with oedema. The survival time in many of these patients is not long enough to allow them to develop typical signs of Cushing's syndrome though they are often highly pigmented. These patients are easily diagnosed. However, patients with small tumours which do not cause very elevated ACTH-levels and who have the more typical clinical signs of full-blown Cushing's syndrome are difficult to recognize. For the differential diagnosis of ACTH-dependent Cushing's syndrome the corticotropin-releasing hormone (CRH) stimulation test and dexamethasone suppression test with high doses are helpful. In special cases the venous sampling procedure for ACTH-measurements is necessary, also CT or NMR is helpful. Ectopic CRH-production is a rare cause of ACTH-dependent Cushing's syndrome. Patients with ectopic CRH-production and consecutive ACTH-hypersecretion from the pituitary have not been studied extensively. There are especially no well documented results of the use of the CRH-stimulation test in vivo in this group of patients with Cushing's syndrome. On the other hand, in the documented cases, not only CRH-, but also ACTH-production was found in the tumours. So far, this rare cause of ACTH-dependent Cushing's syndrome has to be excluded or confirmed by the measurement of endogenous CRH-levels. But until now we have not been able to detect one single case of ectopic CRH-production using a sensitive homologous CRH-radioimmunoassay over a period of more than 8 years in which we have seen nearly 120 newly diagnosed patients with ACTH-dependent Cushing's syndrome. Only in the plasma and tumour tissue of two patients of other groups have we found high CRH-levels.
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PMID:Ectopic production of ACTH and corticotropin-releasing hormone (CRH). 132 73

An 'antisense' peptide ('HTCA'), whose sequence was generated by reading the antisense RNA sequence corresponding to ACTH (1-24) was shown to bind ACTH (1-24) with a Kd of 0.3 nM in a solid-matrix binding assay [( 1986) Biochem. J. 234, 679 683]. Two-dimensional NMR spectra were used to examine the conformational behavior in methanol and in water solution of two fragments of adrenocorticotropin, ACTH(1-24) and ACTH (1-13), as well as their antisense peptides, HTCA and HTCA(12-24). The conformations are extended chains in these solutions, both as isolated molecules and when mixed with their antisense complements. The Kd values are greater than 1 mM.
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PMID:Conformational behavior of fragments of adrenocorticotropin and their antisense peptides determined by NMR spectroscopy and CD spectropolarimetry. 254 6

Previous reports have emphasized the value of bilateral and simultaneous catheterization of the inferior petrosal sinus for the measurement of both basal and oCRH (ovine Corticotropin Releasing Hormone) stimulated ACTH levels to determine the site of the microadenoma in the pituitary and for the differential diagnosis of Cushing's disease. This method is mainly employed in those patients whose hormonal studies are ambiguous and whose CT-scans and NMR (Nuclear-Magnetic-Resonance) results yield inconclusive or negative findings. Ten patients were studied: 9 were under evaluation for Cushing's disease and one was a "relapse" (4 yrs after transsphenoidal microadenomectomy). In all patients, except two who are awaiting surgery and one who was a "relapse", surgical findings were consistent with the ipsilateral hypersecretion (one had a central microadenoma). These results confirm that bilateral and simultaneous catheterization of the inferior petrosal sinus associated with a oCRH stimulus could be of great help in localizing the site of the adenoma and therefore improve the results of surgery. Moreover, this methodology may be of great value in diagnosing ectopic secretion.
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PMID:[Use of catheterization of the inferior petrosal sinus in the diagnosis of Cushing's disease]. 255 88

Two side-chain cyclic lactam analogues of the 4-11 fragment of alpha-melanocyte-stimulating hormone (alpha-MSH), Ac-[Nle4,D-Orn5,Glu8]alpha-MSH4-11-NH2 and Ac-[Nle4,D-Orn5,D-Phe7,Glu8]alpha-MSH4-11-NH2, were prepared on p-methylbenzhydrylamine resin by using a combination of N alpha-Boc and N alpha-Fmoc synthetic strategies with diphenyl phosphorazidate mediated cyclization. The melanotropin activities of these two analogues were examined and compared relative to those of alpha-MSH, Ac-[Nle4]alpha-MSH4-11-NH2, and Ac-[Nle4,D-Phe7]alpha-MSH4-11-NH2. In the frog (Rana pipiens) skin bioassay, the L-Phe7 17-membered ring cyclic analogue was slightly more potent than the linear Ac-[Nle4]alpha-MSH4-11-NH2 and exhibited prolonged melanotropic bioactivity (greater than or equal to 4 h). In this same assay, the D-Phe7 cyclic analogue was more than 100-fold less potent than the L-Phe cyclic analogue and was 10,000 times less potent than linear Ac-[Nle4,D-Phe7]alpha-MSH4-11-NH2. In the lizard skin (Anolis carolinensis) bioassay, the L-Phe7 cyclic analogue was 100-fold less potent than Ac-[Nle4]alpha-MSH4-11-NH2, while the D-Phe7 cyclic analogue was 10,000-fold less potent than both Ac-[Nle4]alpha-MSH4-11-NH2 and the D-Phe7 linear derivative Ac-[Nle4,D-Phe7]alpha-MSH4-11-NH2. The solution conformation of these two cyclic analogues in dimethyl sulfoxide-d6 was examined by 1D and 2D 500-MHz 1H NMR spectroscopy. Our analysis suggests an H bond stabilized C10 (or C13) turn for the D-Phe7 cyclic structure while the L-Phe7 analogue is more conformationally flexible.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic lactam analogues of Ac-[Nle4]alpha-MSH4-11-NH2. 285 55

The 1H NMR spectra of human beta-endorphin indicate that the peptide exists in random-coil form in aqueous solution but becomes helical in mixed solvent. Thermal denaturation NMR experiments show that in water there is no transition between 24 and 75 degrees C, while a slow noncooperative thermal unfolding is observed in a 60% methanol-40% water mixed solvent in the same temperature range. These findings are consistent with circular dichroism studies by other workers concluding that beta-endorphin is a random coil in water but that it forms 50% alpha-helix or more in mixed solvents. The peptide in the mixed water-methanol solvent was further studied by correlated spectroscopy (COSY) and nuclear Overhauser effect spectroscopy (NOESY) experiments. These allow a complete set of assignments to be made and establish two distinct stretches over which the solvent induces formation of alpha-helices: the first occurs between Tyr-1 and Thr-12 and the second between Leu-14 and extending to Lys-28. There is evidence that the latter is capped by a turn occurring between Lys-28 and Glu-31. These helices form at the enkephalin receptor binding site, which is at the amino terminus, and at the morphine receptor binding site, located at the carboxyl terminus [Li, C. H. (1982) Cell (Cambridge, Mass.) 31, 504-505]. Our findings suggest that these two receptors may specifically recognize alpha-helices.
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PMID:Secondary structure determination of human beta-endorphin by 1H NMR spectroscopy. 296 Mar 78

Our attempts to develop adrenocorticotropic hormone (ACTH) analogues that can be employed for ACTH receptor identification and isolation began with the synthesis of ACTH fragments containing N epsilon-(dethiobiotinyl)lysine (dethiobiocytin) amide in position 25 to be used for affinity chromatographic purification of hormone-receptor complexes on Sepharose-immobilized avidin resins. Because labeling ACTH or ACTH fragments by conventional iodination techniques destroys biological activity due to oxidation of Met4 and incorporation of iodine into Tyr2, we have prepared [Phe2,Nle4]ACTH1-24, [Phe2,Nle4,biocytin25]ACTH1-25 amide, and [Phe2,Nle4,dethiobiocytin25]ACTH1-25 amide by conventional synthetic techniques. The HPLC profiles and amino acid analyses of the final products indicate that the materials are of a high degree of purity. The amount of tertiary butylation of the Trp residue in the peptides was assessed by NMR and was found to be less than 0.5%. All three peptides are equipotent with the standard ACTH1-24 as concerns their ability to stimulate steroidogenesis and cAMP formation in bovine adrenal cortical cells. Iodination of [Phe2,Nle4]ACTH1-24, with iodogen as the oxidizing agent, has been accomplished without any detectable loss of biological activity. The mono- and diiodo derivatives of [Phe2,Nle4]ACTH1-24 have been prepared, separated by HPLC, and assayed for biological activity. Both peptides have the full capacity to stimulate steroidogenesis and cAMP production in bovine adrenal cortical cells.
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PMID:Radioactive probes for adrenocorticotropic hormone receptors. 300 27

1H-NMR spectra at 600 MHz and 270 MHz and photo-chemically induced dynamic nuclear polarization (photo-CIDNP) spectra at 360 MHz of beta-endorphin in the presence of sodium dodecyl sulfate (SDS) micelles are reported and discussed in terms of structural changes and immobilization upon binding. On addition of micelles several NH protons show slow H-D exchange rate in 2H2O at p2H 4.6, 25 degrees C, which indicates that some regions of the polypeptide are buried and shielded from the direct interaction with the solvent. Moreover, in the methyl region of the spectrum strong changes are detected both in chemical shifts and line-widths, suggesting an appreciable interaction between the hydrophobic residues of beta-endorphin and the detergent micelles. All aromatic residues are strongly affected by the presence of SDS, supporting the notion that beta-endorphin can interact with both the hydrophobic and hydrophilic portion of the micelles. At physiological pH photo-CIDNP experiments indicate that SDS has about the same immobilizing effect on Tyr-1 and Tyr-27 as n-dodecylphosphorylcholine.
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PMID:Interaction of beta-endorphin with sodium dodecyl sulfate in aqueous solution. 1H-NMR investigation. 609 79

The effect of biologically active peptides (adrenocorticotropin, parathyroid hormone, calcitonin, prolactin) and steroids (aldosterone, progesterone, testosterone) hormones on NMR-relaxation proton of tissue water of kidney have been investigated in vitro. Results of this study suggest that peptide hormones caused dehydration of tissues via sodium regulation. Steroids, quite on the contrary, caused the hydration of kidney tissue independent of the movement of osmotic active electrolyte.
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PMID:[Action of biologically active peptides and steroids on nuclear magnetic resonance relaxation of protons of kidney tissue water in vitro]. 929 6

The earlier reported inhibition of rat liver nucleotide pyrophosphatase/phosphodiesterase I (EC 3.1.6.9/EC 3.1.4.1; NPP/PDE) by culture-grade acidic fibroblast growth factor (FGF-1) correlates with a low-Mr contaminant. 1H-NMR analyses revealed EDTA in the total-volume fractions of a gel-filtration experiment, where all the inhibitory activity of the FGF-1 preparation was recovered. NPP/PDE inhibition by EDTA (and by unfractionated FGF-1 or the EDTA-containing fractions) was time-dependent, blocked by the substrate p-nitrophenyl-dTMP, and strongly enhanced by glycine. The use of glycine buffers in earlier work was critical to the apparent inhibition by FGF-1. The results point to a conformational change favored by glycine that may be relevant to the biological role of NPP/PDE.
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PMID:Glycine-enhanced inhibition of rat liver nucleotide pyrophosphatase/phosphodiesterase-I by EDTA: a full account of the reported inhibition by commercial preparations of acidic fibroblast growth factor (FGF-1). 946 44


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