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)

Peptide E is a 25-amino acid peptide derived from proenkephalin A that was originally isolated from the bovine adrenal medulla. Bovine peptide E (BPE), which possesses a Met- and a Leu-enkephalin sequence at its N- and C-terminus, respectively, has been described as a highly potent and selective mu-opioid receptor agonist. Paradoxically, the frog counterpart of peptide E (FPE), which exhibits only two amino acid substitutions (Met15-->Gln and Leu25-->Met) compared with BPE, was found to be totally devoid of antinociceptive activity. To decipher this apparent discrepancy, we have decided to compare the structural and pharmacological characteristics of FPE, BPE, and the chimeric peptide [Gln15]BPE (Q15BPE). In methanol, all three peptides exhibited virtually the same conformation, the central region of each peptide (residues 10-20) being involved in a regular helix. Intracerebroventricular administration of FPE, BPE, or Q15BPE, at doses up to 1000 ng per mouse, did not induce any analgesic effects, as evaluated by the hot plate and writhing tests, whereas, in the same tests, beta-endorphin at a dose of 100 ng provoked profound analgesia. Concomitant administration of FPE, BPE, or Q15BPE (100 ng) with the aminopeptidase-N inhibitor bestatin (50 microg) or the endopeptidase 24-11 inhibitor thiorphan (10 microg) did not produce analgesic responses. Antinociceptive effects were only observed when very high doses of FPE, BPE, and Q15BPE (10000 ng per mouse) were administered. These data clearly demonstrate that, contrary to what has been previously reported, peptide E is virtually devoid of opioid activity.
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PMID:The proenkephalin A-processing product peptide E, which encompasses two enkephalin sequences, has a much lower opioid activity than beta-endorphin. 1047 88

Beta-endorphin is the largest natural opioid peptide. The knowledge of its bioactive conformation might be very important for the indirect mapping of the active site of opioid receptors. We have studied beta-endorphin in a variety of solution conditions with the goal of testing the intrinsic tendency of its sequence to assume a regular fold. We ran NMR experiments in water, dimethylsulfoxide and aqueous mixtures of methanol, ethylene glycol, trifluoroethanol, hexafluoracetone trihydrate and dimethylsulfoxide. The solvent in which the peptide is more ordered is the hexafluoracetone trihydrate/water mixture. The helical structure detected for beta-endorphin in this mixture at 300 K extends for the greater part of its address domain, hinting at a possible mechanism of interaction with opioid receptors: a two-point attachment involving an interaction of the helical part of the address domain (PLVTLFKNAIIKNAY) with one of the transmembrane helices and a classical interaction of the message domain (YGGF) with the receptor subsite common to all opioid receptors.
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PMID:Solution structure of human beta-endorphin in helicogenic solvents: an NMR study. 1052 84

In this paper, we describe a general procedure to evaluate the thermodynamics of the interaction between polypeptides and hydrophobic ligands in the presence of aquo-organic solvent mixtures. These studies address experimental requirements for the determination of the linear free energy relationships, derivation of partition coefficients or other extrathermodynamic parameters such as contact areas, or assessment of the conformational changes that may occur when polypeptides or proteins interact with immobilized nonpolar ligands. Not unexpectedly from thermodynamic arguments, the trends and magnitudes of free energy parameters, such as the enthalpy of association, as previously derived in many studies from gradient elution reversed-phase high-performance liquid chromatographic (RP-HPLC) measurements are often different from the data for the same parameters derived from equilibrium binding or microcalorimetric determinations. To reconcile these divergencies and to more closely examine the thermodynamic basis of the interaction of polypeptides with nonpolar ligands, the dependency of the logarithmic capacity factor, ln k', on temperature, T, for several polypeptides (bombesin, beta-endorphin, glucagon) have been investigated using a n-butylsilica and acetonitrile-water or methanol-water mixtures of defined solvent compositions. With low-pH, acetonitrile-water mixtures, the van't Hoff plots, i.e., the plots of ln k' versus 1/T, were nonlinear over the range of T = 278-358 K, although within a narrow temperature range, e.g., from T = 278-308 K, the experimental data for these polypeptides could be approximated by a linear relationship. This nonclassical van't Hoff behavior was associated with interactive processes that involved temperature-dependent enthalpic, entropic, and heat capacity changes. In contrast, with low-pH, methanol-water mixtures, the van't Hoff plots showed dependencies that were essentially linear over the range of T = 278-358 K. The slopes of the van't Hoff plots with acetonitrile-water and methanol-water mixtures at a defined T value and solvent composition were significantly larger than those found for the corresponding experiments carried out under gradient elution RP-HPLC conditions. From these plots of ln k' versus 1/T, the changes in the apparent enthalpy of association (delta H++assoc) and the apparent entropy of association (delta S++assoc) for the interaction of these polypeptides with the solvated n-butyl ligands at different T and solvent compositions have been determined. For these polypeptides, both delta H++assoc and delta S++assoc exhibited linear dependencies on the volume fraction, phi, of the organic solvent over a narrow range of T, but the slopes of these plots were dependent on the T range examined. The dependencies of the slope term, S, and the intercept term, ln ko, derived from the plots of ln k' versus phi as a function of T, have also been investigated. A new relationship linking the S values with delta H++assoc and delta S++assoc as a function of T and phi has been derived and validated. In addition, the relationship between S, delta H++assoc, delta S++assoc, the apparent change in heat capacity, delta C++assoc, and the accessible surface area, delta Atot, of these polypeptides has been examined, thus providing a linkage of these thermodynamic and extrathermodynamic parameters to the partition coefficient, P, and the molecular properties of these polypeptides. The results confirm that entropy-enthalpy compensation effects participate in the interaction of polypeptides with hydrophobic ligands. This investigation has confirmed that the use of solvent-water mixtures of defined composition, rather than the more convenient practice of using gradient elution methods, is essential if thermodynamically consistent values of the binding affinities and partition coefficients are to be quantitatively derived. (ABSTRACT TRUNCATED)
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PMID:Investigations into the thermodynamics of polypeptide interaction with nonpolar ligands. 1056 77

Rat liver nucleotide pyrophosphatase/phosphodiesterase I (NPP/PDE) catalysed efficiently the transfer of adenylate from ATP to alcohols (methanol, ethanol, propanol, ethylene glycol, glycerol, 2, 2-dichloroethanol and glycerol 2-phosphate), which acted as adenylate acceptors competing with water with different efficiencies. NPP/PDE kinetics in alcohol/water mixtures were accounted for by rate equations for competitive substrates, modified to include alcohol negative co-operativity and, depending on the nature of the alcohol, enzyme denaturation by high alcohol concentrations or activation by low alcohol concentrations. The correlation of alcohol efficiencies with alcohol acidities, the comparison of rat liver with snake venom NPP/PDE, and the different effects of ionic additives on the efficiencies of glycerol 2-phosphate and glycerol provided evidence for interaction of the alcohols with a base catalyst, a non-polar and a cationic subsite in the active centre of rat liver NPP/PDE. The enzyme thus appears to be well suited to act as transferase, and we propose that NPP/PDE could be an adenylylating agent in the membrane.
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PMID:Rat liver nucleotide pyrophosphatase/phosphodiesterase is an efficient adenylyl transferase. 1065 35

The coordination chemistry of the potentially semilabile tridentate ligand 2-pyridylbis(diphenylphosphino)methane (NPP) has been investigated. Bidentate (N, P) coordination occurs in CoCl(2)(NPP) (1) and [CdX(mu-X)(NPP)](2) (X = Cl (2); OAc (3)), prepared from the corresponding metal salts, in fac-Re(CO)(3)Br(NPP) (4) and in Fe(CO)(2)(MA)(NPP) (6). The last is one of three products from the reaction of Fe(CO)(4)(MA) (MA = maleic anhydride) with NPP, the other two being Fe(CO)(3)(NPP) (7; P, P coordinated) and the unusual cyclic ylid Ph2PC(2-C5H4N)PPh2C(CH2CO2H)C(=O)(5). The ligand shows tridentate coordination in Cr(CO)(3)(NPP) (9), RuCl(2)(PPh(3))(NPP) (10), and possibly in PtCl(2)(NPP) (8). Carbon monoxide displaces one phosphorus arm of the ligand in 10. Anhydrous NiCl(2) and NPP react in the presence of methanol to give NiCl(2)(P(OMe)Ph(2))(Ph(2)PCH(2)py) (12) in which the NPP ligand has been cleaved. This in turn reacts with O(2) to form trans-NiCl(2)(Ph(2)P(O)CH(2)py)(2) (13). The methine proton of NPP is transferred to the metal on reaction with Pt(C(2)H(4))(PPh(3))(2) and [Ir(COD)(NPP)]BF(4) to form the hydride complexes Pt(H)(PPh(3))(NPP-H) (14) and [Ir(H)(NPP)(NPP-H)]BF(4) (15). In 15 the intact NPP ligand is tridentate. The structures of 1 - 7 and 12 - 15 have been determined.
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PMID:Synthetic and structural studies of the coordination behavior of 2-pyridylbis(diphenylphosphino)methane. 1131 55

Because of a wide range of physiological functions, the structure of beta-endorphin (BE) is of great interest. In this study, conformational changes in BE induced by methanol are explored with electrospray ionization-mass spectrometry (ESI-MS). Differences in the charge-state distribution (CSD) and the extent of hydrogen/deuterium (H/D) exchange were used to monitor the conformational changes. The latter experiments were conducted via time-resolved ESI-MS in a continuous-flow apparatus. Both these techniques demonstrate that BE exists in a random coil open structure in aqueous media, but it acquires a more compact conformation with increased concentration of methanol. The H/D exchange experiments reveal that BE forms 61% alpha-helix in mixed solvents.
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PMID:Conformational changes in beta-endorphin as studied by electrospray ionization mass spectrometry. 1174 1

The Steller sea lion (Eumetopias jubatus) is listed as endangered in parts of its range and is suspected of suffering from ecological stressors that may be reflected by fecal glucocorticoid hormones. We validated a fecal glucocorticoid assay for this species with an adrenocorticotropic hormone (ACTH) challenge. Feces were collected from captive Steller sea lions (two males and two females) for 2 days before injection with ACTH, and for 4 or more days postinjection. Feces were freeze-dried, extracted with a methanol vortex method, and assayed for glucocorticoids. The assay demonstrated good parallelism and accuracy. All animals showed the expected peak of fecal glucocorticoid excretion after ACTH injection. However, the two males had higher baselines, higher peaks, and more delayed peaks than the females. Peak glucocorticoid excretion occurred at 5 and 28 h postinjection for the two females, and at 71 and 98 h for the two males. Correction for recoveries by the addition of tritiated hormones produced ACTH profiles that were virtually identical in pattern to uncorrected data, but with higher within-sample coefficients of variation. Based on these results, we conclude that this fecal glucocorticoid assay accurately reflects endogenous adrenal activity of Steller sea lions, and that recovery corrections are not necessary for this species when using the methanol vortex extraction method. More research is needed to address possible sex differences and other possible influences on fecal glucocorticoid concentrations.
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PMID:Validation of a fecal glucocorticoid assay for Steller sea lions (Eumetopias jubatus). 1498 91

High concentrations (up to 600 pg/ml) of corticotropin-releasing hormone (CRH) were detected in plasma of the teleost fish Oreochromis mossambicus (tilapia) when screening peripheral tissues of tilapia exposed to stress. Notably, the plasma CRH response to stressors in tilapia is much more pronounced than that in higher vertebrates, such as rats. After characterisation by RIA, by spiking plasma with synthetic tilapia CRH and by methanol-acid extraction, it is concluded that the immunoreactive (ir) material in plasma represents tilapia CRH(1-41). Results indicate that a CRH-binding protein is absent in tilapia plasma. Unstressed fish had plasma CRH levels under the limit of detection (<2 pg/ml), but following capture stress plasma CRH levels (170-300 pg/ml) as well as plasma cortisol levels (120 ng/ml) increased rapidly to plateau levels, which were reached after approximately 5 min. Tilapia CRH(1-41) tested at concentrations between 10(-11) and 10(-7) M in vitro did not stimulate the cortisol release from interrenal tissue. Also pretreatment of interrenal tissue with 10(-9) M CRH did not sensitise the cortisol-producing cells to a subsequent ACTH challenge. Forty-eight hours of net confinement or 48 h of cortisol treatment abolished the plasma CRH response and cortisol response to capture stress. The rapidity of the plasma CRH response and its inhibition after 48 h of stress or cortisol treatment point to release by central nervous tissue. Therefore the distribution of glucocorticoid receptors (GRs) in the brain and pituitary of tilapia was investigated. Main GR-ir cell clusters were found in the medial part (Dm) and posterior part of the dorsal telencephalon, in the preoptic region, in the inferior lobe of the hypothalamus and in the cerebellum. We conclude from comparison of CRH brain contents of unstressed and stressed fish that plasma CRH was released by CRH-ir cells located in the lateral part of the ventral telencephalon (Vl), and suggest that the cortisol feedback on CRH release by Vl is mainly exerted via the forebrain Dm region. We propose that CRH is mobilised during stress to fulfil peripheral functions, such as the regulation of circulating leukocytes or of cardiac output, as CRH receptors have been reported in these organs for fish species.
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PMID:Corticotropin-releasing hormone in the teleost stress response: rapid appearance of the peptide in plasma of tilapia (Oreochromis mossambicus). 1501 97

Bioassay-guided fractionation of Curcuma longa by solvent partitioning and purification with octadecylsilane open column chromatography yielded a partial purification. The active 80% methanol chromatographic fraction from the ethyl acetate layer [partial purification from C. longa (PPC)] was used to investigate the alpha-melanocyte-stimulating hormone (alpha-MSH)-stimulated melanogenesis signal pathway in B16F10 cells. In cells stimulated alpha-MSH, PPC inhibited cellular melanin contents, tyrosinase activity and expression of melanogenesis-related proteins including microphthalmia-associated transcription factor (MITF), tyrosinase and tyrosinase-related proteins (TRP). Melanogenesis-regulating signalling such as mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/Akt was activated by PPC in alpha-MSH-stimulated B16F10 cells. The suppressive activity of PPC on alpha-MSH-induced melanogenesis was abrogated by selective inhibition of MEK/ERK (PD98059) and PI3K (LY294002). MEK/ERK or Akt activation by PPC may contribute to reduced melanin synthesis via MITF and its downstream signal pathway including tyrosinase and TRPs in alpha-MSH-induced melanogenesis.
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PMID:Partially purified Curcuma longa inhibits alpha-melanocyte-stimulating hormone-stimulated melanogenesis through extracellular signal-regulated kinase or Akt activation-mediated signalling in B16F10 cells. 1946 2

A new iridoid glycoside, 9-epi-6alpha-methoxy geniposidic acid (4), three new hemiterpene glycosides, 3-methylbut-3-enyl 2'-O-(beta-D-glucopyranosyl)-beta-D-glucopyranoside (nonioside K) (6), 3-methylbut-3-enyl 6'-O-(beta-D-xylopyranosyl)-beta-D-glucopyranoside (nonioside L) (8), and 3-methylbut-3-enyl 6'-O-(beta-D-xylofuranosyl)-beta-D-glucopyranoside (nonioside M) (9), and two new saccharide fatty acid esters, 6'-O-(beta-D-glucopyranosyl)-1'-O-[(2xi)-2-methylbutanoyl]-beta-D-glucopyranose (nonioside N) (16) and 6'-O-(beta-D-xylopyranosyl)-1'-O-[(2xi)-2-methylbutanoyl]-beta-D-glucopyranose (nonioside O) (17), were isolated from a methanol extract of the fruits of Morinda citrifolia (noni), along with 11 known compounds, namely, three iridoid glycosides (1-3), two hemiterpene glycosides (5 and 7), and five saccharide fatty acid esters (10-15). Upon evaluation of compounds 1-17 on the melanogenesis in the B16 melanoma cells induced with alpha-melanocyte-stimulating hormone (alpha-MSH), 13 compounds (1, 3, 4, 6-14, and 17) exhibited marked inhibitory effects with 34-49% reduction of melanin content at 100 muM with no or almost no toxicity to the cells (91-116% of cell viability at 100 microM).
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PMID:Melanogenesis inhibitory activities of iridoid-, hemiterpene-, and fatty acid-glycosides from the fruits of Morinda citrifolia (Noni). 2003 99


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