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

[Gly8]beta hEP(1-27)NH2 and [L-Leu8]beta hEP(1-27)NH2, two analogs of human beta-endorphin, were synthesized by both all-stepwise solid phase synthesis and peptide segment coupling. For the peptide segment coupling method, two thiocarboxyl peptides. Msc-[Gly8]beta hEP(1-8)SH and Msc-[L-Leu8]beta hEP(1-8)SH, were synthesized by standard solid phase method on 4-[alpha-(Boc-Gly-S)benzyl]phenoxyacetamidomethy-resin and 4-[alpha-(Boc-L-Leu-S)benzyl]phenoxyacetamidomethy-resin. These two thiocarboxyl peptides were coupled to H-[Lys(Cit)9,19,24]-beta hEP(9-27)NH2. [Gly8]beta hEP(1-27)NH2 and [L-Leu8]beta hEP(1-27)NH2 were obtained after removal of Msc groups and citraconyl groups from products of the segment coupling reaction. The yields of both [Gly8]beta hEP(1-27)NH2 and [L-Leu8]beta hEP(1-27)NH2 in the segment coupling reaction were approximately 18%. Less than 1% of racemization of Leu-8 occurred during coupling of Msc-[L-Leu8]beta hEP(1-8)SH to H-[Lys(Cit)9,19,24]-beta hEP(9-27)NH2. Results of amino acid composition analysis, analysis by reverse phase high pressure liquid chromatography and receptor binding activity assays of the analogs showed that peptide analogs prepared by segment coupling method and those prepared by all-stepwise solid phase synthesis were identical. Results of receptor binding activity assays suggested that the molecular charge properties of beta-endorphin(1-27) and its analogs influenced the receptor binding activity.
 ...
PMID:Chemical synthesis of human beta-endorphin(1-27) analogs by peptide segment coupling. Leucine and glycine residues bearing thiocarboxyl functions as junctions for peptide segment coupling. 165 7

To determine the degree of similarity between pituitary and lymphocyte proopiomelanocortin, the lymphocyte mRNA was reverse transcribed, cloned, and sequenced. Murine lymphocyte mRNA was first purified by oligo(dT)-cellulose affinity chromatography and was reverse transcribed by using a selective 3' antisense oligonucleotide primer directed at the boundary between the translated/nontranslated region on the 3' end of exon 3. This cDNA was then amplified in a polymerase chain reaction with selective primers containing Sal I and Kpn I restriction endonuclease sites. Amplified cDNA was then directionally ligated into M13mp18 and M13mp19 bacteriophage and was sequenced. The nucleotide sequence encoding this peptide was identical to that of mouse pituitary corticotropin (ACTH). Elevated levels of lymphocyte immunoreactive ACTH were then induced with bacterial lipopolysaccharide and the peptide(s) was purified by antibody affinity chromatography and reverse-phase high-performance liquid chromatography. The predominant immunoreactive ACTH species was approximately 3 kDa and its sequence was identical to pituitary ACTH(1-25). These results conclusively demonstrate that lymphocytes produce authentic ACTH and harbor its mRNA.
 ...
PMID:Nucleotide and amino acid sequence of lymphocyte-derived corticotropin: endotoxin induction of a truncated peptide. 168 57

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)
 ...
PMID:Cyclic lactam analogues of Ac-[Nle4]alpha-MSH4-11-NH2. 285 55

Cultured cells from adult rat anterior pituitaries or intermediate lobes were treated with the proteinase inhibitor tripeptide aldehydes BOC-DPhe-Pro-Arg-H (Boc-fPRH) and DPhe-Pro-Arg-H (fPRH), ovine corticotropin-releasing factor (oCRF), and bromocriptine. One millimolar fPRH stimulated basal, and slightly enhanced oCRF-induced ACTH release by melanotrophs in short-term experiments. The basal release of alpha-MSH was also stimulated by the drug. In long-term experiments, fPRH elevated markedly both the release and the intracellular level of ACTH; BOC-fPRH caused an increased alpha-MSH release. Tritiated fPRH had no preference for POMC-producing cells and BOC-fPRH or fPRH were harmless to the cell morphology. In anterior pituitary cell cultures, fPRH diminished slightly basal and oCRF-induced ACTH release. Bromocriptine was ineffective on corticotrophs, however, in melanotrophs it inhibited ACTH release markedly with or without fPRH in the medium. The dissimilar responsiveness of the corticotrophs and melanotrophs to the peptide aldehydes may be interpreted in terms of their differing membrane receptors or intracellular mechanism of stimulus-secretion coupling.
 ...
PMID:Dissimilar responsiveness of cultured corticotrophs and melanotrophs to tripeptide aldehydes. 301 10

Cultured cells from adult rat anterior pituitaries and intermediate lobes were treated with proteinase inhibitor substrate analogues (Boc-DPhe-Pro-Arginal [BOC-DPPA], DPhe-Pro-Arginal [DPPA], BOC-DPhe-Leu-Lysinal [BOC-DPLL], BOC-DPhe-Phe-Lysinal [BOC-DPPL]) to elucidate their effect on cell morphology. It was established that BOC-DPPA and DPPA (which in previous studies stimulated alpha-MSH release [6]) caused a slight decrease in the number of immunoreactive secretory granules in melanotrophs. BOC-DPLL, which inhibited growth hormone and prolactin release, did not alter the fine structural features of cultured cells. No difference was observed in the membrane turnover traced by cationic ferritin when cells were treated with BOC-DPPL. We suggest that substrate analogues used are harmless to pituitary cells.
 ...
PMID:Proteinase inhibitors while influencing hormone release do not affect cell morphology of hypophyseal cultures. 313 79

The effects of a potent serine protease inhibitor, Boc-D-Phe-Pro-Arg-H, on the secretion and content of ACTH and beta-endorphin-like immunoreactivities of cultured rat anterior pituitary cells were studied. Basal release of the hormones was not affected by the drug but secretion in response to stalk-median eminence extracts was inhibited. The inhibitor did not effect the amount of ACTH or beta-endorphin in the medium plus the cells, nor did it change the ratio of the lipotropin and beta-endorphin-like immunoreactivities. Thus the compound seems to affect the release of ACTH and beta-endorphin, but not the processing of lipotropin to beta-endorphin.
 ...
PMID:A serine-proteinase inhibitor (Boc-D-Phe-Pro-Arg-H) inhibits the secretion of adrenocorticotropin- and beta-endorphin-immunoreactive peptides in vitro. 629 20

It has been suggested that a pituitary-derived or -dependent factor may suppress enkephalin peptide synthesis in the central noradrenaline- containing cells of the sheep adrenal medulla in late gestation. We have investigated the effect of thyroxine (T4) replacement after fetal hypophysectomy on the localisation of enkephalin peptides within the peripheral adrenaline- and central noradrenaline-containing regions of the adrenal medulla of the fetal sheep. Fetal hypophysectomy (HX) was performed in 12 fetal sheep at 105-108 days gestation (term = 145 +/- 3 days gestation). T4 (40 micrograms/kg/24h) (HX + T4) or saline (HX + Sal) were infused between 110 and 140 days gestation. Adrenal glands were collected from the HX + T4, HX + Sal groups and from a group of intact fetal sheep (n = 4) for immunohistochemistry using anti- met-enkephalin and an avidin-biotin staining system. In adrenals from intact fetal sheep, there was intense positive staining for met-enkephalin in the peripheral adrenaline-containing region and sparse staining for enkephalins in the central noradrenaline-containing region. In contrast, in the HX + Sal group, enkephalin staining was uniformly present throughout the peripheral and central regions of the adrenal medulla. In the HX + T4 group, however, the staining density of met-enkephalin was higher within the adrenaline cells of the peripheral rim of the medulla than in the central medullary region. We have demonstrated that T4 replacement after fetal hypophysectomy restores the normal ontogenetic pattern of localisation of enkephalin peptides within the fetal adrenal. We postulate that T4 acts either indirectly via neural mechanisms or directly at the noradrenaline-containing cells to mediate the suppression of enkephalin staining within the central noradrenaline-containing region of the adrenal medulla of the fetal sheep in late gestation.
 ...
PMID:Thyroxine replacement after hypophysectomy alters the pattern of enkephalin localisation in the adrenal medulla of the fetal sheep. 881 66

Tetra-O-acetylgalactopyranosylamine and tetra-O-acetylglucopyranosylamine of D-Met2, Pro5 enkephalin were designed and synthesized to enhance their membrane penetration, biological activity and resistance to proteolytic hydrolysis. Three approaches to the synthesis were attempted, which lead to a new synthetic scheme with a higher yield and enhanced ease of purification. The improved procedure involved attaching the tetra-O-acetylglycopyranosylamine to a t-Boc-Gly-Phe-Pro-OH peptide, removing the t-Boc, and condensing it with t-Boc-Tyr-D-Met-OH. Biological evaluation in vivo showed that these acetylglycopyranosylamine derivatives bind to mu and delta opioid receptors in homogenate binding assays and possess analgesic activity. The analgesic potency was less than that of the parent compound D-Met2, Pro5 enkephalin. These acetylglycopyranosylamine derivatives showed enhanced lipophilicity compared to their parent compound by a partition coefficient study and they also showed greater membrane permeability, using the rabbit cornea as a model system. These derivatives also are resistant to hydrolytic enzymes as compared to the endogenous met-enkephalin when evaluated in homogenized iris-ciliary body and aqueous humor from rabbit eyes.
 ...
PMID:Synthesis and antinociceptive activity of [D-Met2, Pro5] enkephalin [N1,5-beta-D-2,3,4,6-O-tetraacetylglycosyl]--amide and [D-Met2, Pro5] enkephalinamide. 934 51

The stability of tert-butoxycarbonyl-Tyr-Leu-Val-CH2Cl (YLV) with inhibitory effect on human leukocyte elastase was investigated in aqueous solution, alpha-chymotrypsin solution and biological media. In all cases studied here, the degradation was observed as a pseudo-first order reaction. The half-life for the degradation of YLV in an aqueous solution of pH 7.4 at 37 degrees C was 35.9 h. YLV was most stable at about pH 3.8-5.8 and the effect of temperature was explained by the Arrhenius equation. The activation energies of the degradation in aqueous solutions at pH 2.0, 4.8, and 7.4 were 24.6, 22.1 and 23.4 kcal/mol, respectively. The degradation products in aqueous solution were analyzed by HPLC-MS and were estimated as Boc-Tyr-Leu-Val-CH2OH at pH 7.4 and H2N-Tyr-Leu-Val-CH2Cl at pH 2.0. In a bovine pancreas alpha-chymotrypsin solution at 37 degrees C, the half-life of YLV was 15 min at 25.6 micrograms/ml of alpha-chymotrypsin solution. In the rat plasma, the half-life of YLV was 42.4 min (YLV 26.7 micrograms/ml plasma), and in rat liver, lung and spleen homogenates, the degradation rate constants of YLV were 37.6, 10.3 and 23.5 times larger than that in plasma solution, respectively (all fluids containing 5 mg protein/ml). YLV was less stable than nafarelin acetate, secretin, adrenocorticotropic hormone (ACTH) and gonadorelin in an aqueous solution of pH 7.4.
 ...
PMID:Degradation of a novel tripeptide, tert-butoxycarbonyl-Tyr-Leu-Val-CH2Cl, with inhibitory effect on human leukocyte elastase in aqueous solution and in biological fluids. 939 62

The 2-(4-nitrophenylsulfonyl)ethoxycarbonyl (Nsc) group is a new base-labile protecting group for solid-phase peptide synthesis, completely interchangeable with the fluorenylmethoxycarbonyl (Fmoc) protecting group, but with certain advantages. In this paper, we report a methodology with Nalpha-Nsc-protected amino acids for the synthesis of some melanotropins important to our research, namely, gamma-melanocyte-stimulating hormone (gamma-MSH), its [Nle3]-analogue, and a cyclic alpha-MSH/beta-MSH hybrid. We developed an efficient protocol for the synthesis of the cyclic MSH analogue that yielded this peptide in >98% purity. The gamma-MSH synthesis, which gave problems with both the Boc and Fmoc strategies, yielded the desired peptide by Nsc-chemistry but was accompanied by side products. Finally, the Nle3-gamma-MSH analogue was synthesized more efficiently using the Fmoc strategy, suggesting that Nsc-chemistry might not be the best methodology for certain sequences.
 ...
PMID:Evaluation of new base-labile 2-(4-nitrophenylsulfonyl) ethoxycarbonyl (Nsc)-amino acids for solid-phase peptide synthesis. 1096 41


1 2 Next >>