Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

[1-Alpha-Mercaptoacetic acid, 5-isoasparagine] oxytocin was synthesized to study the effects of moving the side chain carboxamide group of the amino acid residue in position 5 of oxytocin from the beta to the alpha position. The analog has an isoasparagine residue in position 5 and the 20-membered ring size of oxytocin is maintained by substituting cysteine in position 1 of oxytocin by alpha-mercaptoacetic acid. The analog was found to possess 0.098 +/- 0.002 U/mg of uterotonic activity but no milk-ejecting, antidiuretic or rat pressor activity could be detected. The substance did not inhibit the uterotonic or milk-ejecting activity induced by oxytocin nor the antidiuretic or rat pressor responses to the USP posterior pituitary standard. These results, together with the data available in the literature, indicate that an analog of oxytocin lacking the asparagine residue in position 5 is neither an agonist nor an antagonist. The observations may mean that the asparagine residue is critically important for the interaction of oxytocin with its receptor.
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PMID:Studies on the importance of the asparagine residue in oxytocin. Synthesis and some pharmacological properties of [1-alpha-mercaptoacetic acid, 5-isoasparagine] oxytocin. 698 66

A reverse-phase high performance liquid-chromatography (h.p.l.c.) protocol has been developed, whereby all the major known posterior-pituitary components that are derived from the processing of pro-oxytocin and pro-vasopressin can be separated one from another. Thus, in a single chromatographic step, it has been possible to separate vasopressin (VP), oxytocin (OT), oxytocin-neurophysin (rOT-Np), vasopressin-neurophysin (rVP-Np) and vasopressin-glycopeptide (rVP-GP) from acid extracts of the neurointermediate lobes of rat pituitary glands. All these peptides except rVP-GP were labelled in the neural lobe by 24h after a hypothalamic injection of [35S]cysteine, whereas all except VP were labelled by 24h after a similar injection of [3H]leucine. Three major labelled proteins were isolated from 20 min [35S]cysteine-injected rats when extracts of the supraoptic nucleus were subjected to Sephadex G-75 chromatography, h.p.l.c. and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Immunoprecipitation with antisera raised against rat neurophysins, VP and OT revealed 21000- and 19000-mol.wt. common precursors to VP and rVP-Np and a 15000-mol.wt. common precursor to OT and rOT-Np. Some immunoreactive rVP-Np could occasionally be detected in the Vo of Sephadex G-75 chromatograms of Wistar rat supraoptic-nucleus extracts, but no evidence of [35S]neurophysin in this fraction was obtained from h.p.l.c. fingerprinting of its S-carboxymethylated tryptic digests. Radioimmunoassay for rVP-Np and rOT-Np revealed that about 70-80% of the total recovered immunoreactive neurophysin (IR-Np) in the supraoptic nucleus eluted from Sephadex G-75 and h.p.l.c. in the positions of rVP-Np and rOT-Np. Evidence is presented for an approx. 20000-mol.wt. rOT-Np in both Wistar and Brattleboro rats and for an approx. 20000-mol.wt. component in the Brattleboro rat that is recognized by vasopressin-neurophysin antisera.
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PMID:Precursors in the biosynthesis of vasopressin and oxytocin in the rat. Characteristics of all the components in high-performance liquid chromatography. 715 2

Sulfhydryl oxidase is a metalloglycoprotein in milk which catalyzes oxidation of thiols to their corresponding disulfides using molecular oxygen as an electron acceptor. Cysteine, peptides, and proteins all serve as substrates for this oxidative activity. Investigation of the various possible active oxygen species suggests that the enzyme-bound forms of singlet oxygen and a hydroperoxy group may be produced during catalysis. However, the possible intermediate superoxide anions or hydroxyl radicals did not appear to be formed. Evidence was obtained for a direct interaction between sulfhydryl oxidase and horseradish peroxidase which results in an enhancement of the thiol oxidative activity. This interaction also induced a change in the peroxidase absorption spectra consistent with formation of the horseradish peroxidase-II form of the enzyme. Stimulation of oxidase activity also was observed in the presence of oxytocin and certain concentrations of oxidized glutathione.
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PMID:Oxygen activation by sulfhydryl oxidase and the enzyme's interaction with peroxidase. 719 33

[35S]Cysteine-labeled putative precursors for vasopressin-associated neurophysin (NP-VP) and oxytocin-associated neurophysin (NP-OT) were isolated from the supraoptic nuclei (SONs) of normal rats. Homozygous Brattleboro rats were deficient in one of these precursors, the NP-VP precursor. Direct support for the hypothesis that OT and its NP- and VP and its NP are synthesized from two separate macromolecular common precursors was obtained by limited proteolysis of the precursors with trypsin and identification of the fragments as NPs, VP, or OT by a number of criteria (14). In this paper, these common precursors designated propressophysin (precursor for NP-VP and arginine VP) and prooxyphysin (precursor for NP-OT and OT) were further characterized. Propressophysin was specifically bound by Concanavalin-A-Sepharose and was eluted by 0.2 M alpha-methyl mannoside, showing that it is glycosylated. In contrast, prooxyphysin does not appear to be glycosylated. Using [3H]fucose as label injected near the SONs, two proteins (mol wt, approximately 10,000) were identified, which appear to be derived from propressophysin, that are rapidly transported to the posterior pituitary of normal rats. These two proteins were absent in homozygous Brattleboro animals. Both propressophysin and prooxyphysin were bound by a NP-Sepharose affinity support. The binding was different from that of arginine VP or OT to NP, since it was independent of pH and was hydrophobic in nature. In addition to prooxyphysin, the SONs of homozygous Brattleboro rats also contained other [35S]cysteine-labeled protein (mol wt, 20,000) composed of a NP-like protein and NP-binding peptides. The tryptic peptides derived from these proteins were very different in their chromatographic (high performance liquid chromatography) properties than the tryptic peptides derived from propressophysin and prooxyphysin. This protein ('X') was not bound by a Concanavalin-A-Sepharose affinity column, although it had chromatographic properties similar to propressophysin on Sephadex G-75.
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PMID:Biosynthesis of vasopressin, oxytocin, and neurophysins: isolation and characterization of two common precursors (propressophysin and prooxyphysin). 742 96

Disulfide bond formation in S-acetamidomethyl (Acm) cysteine-containing peptides by successive treatments with silver trifluoromethanesulfonate (AgOTf) and dimethyl sulfoxide (DMSO)/aqueous HCl is described. An S-Acm cysteine was found to be quantitatively converted into cysteine by deprotection of the Acm group with AgOTf followed by DMSO/aqueous HCl treatment. Under these reaction conditions, no significant side reactions were observed with oxidation-sensitive amino acids such as Met, Tyr and Trp. Oxytocin and a Trp-containing peptide, urotensin II, were prepared by this method. Furthermore, regioselective two disulfide bond formation was found to be feasible by the combination of air oxidation and the AgOTf-DMSO/HCl system. This strategy has been successfully applied to the syntheses of tachyplesin I and endothelin I, which have two disulfide bonds and a Trp residue in the molecule.
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PMID:Disulfide bond-forming reaction using a dimethyl sulfoxide/aqueous HCl system and its application to regioselective two disulfide bond formation. 760 3

An aminopeptidase from porcine kidney, hydrolyzing oxytocin and vasopressin in vitro, was purified by chromatography on hydroxyapatite, DEAE-cellulose and nickel ion chelate gel and gel filtration on Sephadex G-100. The enzyme appeared to be a high molecular mass (M(r) 105,000) monomeric protein. It was sensitive to inhibition by metal chelator, o-phenanthroline. Cobalt ion and sulfhydryl activator, 2-mercaptoethanol, had activating effects, while p-chloromercuribenzoate, amino acids with large hydrophobic side chains, L-cystine and aminopeptidase inhibitors, bestatin and amastatin, had inhibitory effects on the enzyme activity. The enzyme hydrolyzed several aminoacyl p-nitroanilides, and had the highest specificity against S-benzyl-L-cysteine p-nitroanilide. The properties of the enzyme were distinct from those of well-characterized leucyl aminopeptidase (EC 3.4.11.1), membrane alanyl aminopeptidase (EC 3.4.11.2) and primate placental cystinyl aminopeptidase (EC 3.4.11.3).
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PMID:An aminopeptidase activity from porcine kidney that hydrolyzes oxytocin and vasopressin: purification and partial characterization. 787 63

Cysteamine (CSH), a sulfhydryl agent that promotes disulfide-exchange reactions, was studied for its effects on the immunoreactive (IR) levels and synthesis of oxytocin and vasopressin in the hypothalamus. CSH injection (300 mg/kg s.c.) caused a rapid (1 h) suppression of 35S-cysteine incorporation into hypothalamic arginine vasopressin (VP) and oxytocin (OT). The reduction in labeling persisted for about 8 h; label incorporation was normal within 10 h of CSH administration. The drug did not influence 35S-cysteine incorporation into acid-precipitable protein, nor did it influence 35S-cysteine specific activity in the hypothalamus. In addition, 35S-VP and 35S-OT molecules could not be recovered from hypothalami of CSH-treated rats by subjecting samples to denaturing, reducing and then reoxidizing conditions. Despite the reduction in peptide labeling, CSH treatment produced no alterations in the IR VP and OT contents of hypothalamus or posterior pituitary. These results indicate that CSH causes a true suppression of both VP and OT formation in hypothalamus, and suggest that the effect is either too transient to promote a reduction in endogenous stores of either peptide, or that the drug equally inhibits peptide production and removal (i.e., axonal transport, secretion).
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PMID:Effect of cysteamine injection on vasopressin and oxytocin biosynthesis in rat hypothalamus. 815 71

Peptide contents of neural lobes from adult jerboas (Jaculus orientalis) under different states of hydration were determined by radioimmunoassay. The amounts of vasopressin, oxytocin, and their associated neurophysins in animals dehydrated for up to 4 weeks were not significantly different from those of controls. The different neurohypophyseal peptide were separated on two different types of gradient using reverse-phase high-performance liquid chromatography. The shape of the chromatograms suggests that, in contrast to the case of the rat, for which only three types of neurophysins have been shown, there are, in jerboa, many subspecies of neurophysins. This was also shown using two-dimensional electrophoresis. Injection of [35S]cysteine into the supraoptic nucleus followed by HPLC of extracts from the neural lobes from animals under different states of dehydration showed that the labeled material is not released any faster in dehydrated animals than in controls. Labeled vasopressin, oxytocin, and neurophysins could still be detected by HPLC 4 weeks after injection. Neural lobes from animals injected with [35S]cysteine were perfused in vitro and the release of neuropeptides was triggered by bursts of electrical pulses and also by K(+)-induced depolarization. The amplitude of the rate constant for release and the amounts of vasopressin and of radiolabeled material released were similar in animals dehydrated for up to 3 weeks and in controls. Under physiological conditions similar to those that would be expected to occur in their natural habitat, the jerboas appear to have a hypothalamoneurohypophyseal system which is down-regulated.
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PMID:Synthesis, turnover, and release of peptides from the neurohypophysis of the Jerboa Jaculus orientalis. 819 37

Methodology is described for characterization of the kinetics and equilibria of thiol/disulfide interchange reactions of the disulfide bonds in the neurohypophyseal peptide hormones arginine vasopressin and oxytocin and the related peptides pressinoic acid and tocinoic acid. Thiol/disulfide interchange reaction mixtures are analyzed by reversed-phase high-performance liquid chromatography. The effect of mobile-phase composition and pH on the HPLC capacity factors for the native disulfide and reduced dithiol forms of each peptide was examined. In each case, the capacity factor decreases as the acetonitrile content of the mobile phase increases. For each disulfide/dithiol peptide pair, the capacity factor is larger for the dithiol form of the peptide, indicating that the hydrophobic side chains of the linear peptide are more accessible for interaction with the hydrophobic stationary phase. To illustrate application of the methodology, rate and equilibrium constants are reported for the thiol/disulfide interchange reactions of cysteine with arginine vasopressin at pH 7.0. Cysteine reacts with arginine vasopressin to form two mixed disulfides, which in turn react with another molecule of cysteine to give the dithiol form of arginine vasopressin and cystine. Rate and equilibrium constants were determined for each step by analysis of reaction mixtures by HPLC. The results are compared to rate and equilibrium constants for reaction of cysteine with oxidized glutathione.
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PMID:Characterization of the thiol/disulfide chemistry of neurohypophyseal peptide hormones by high-performance liquid chromatography. 825 69

Disulfide bonds of peptides were effectively established between S-protected cysteine residues as well as free cysteine residues by the action of dimethylsulfoxide in trifluoroacetic acid. Oxytocin and alpha-human calcitonin gene-related peptide were synthesized using this oxidation system. The feasibility of this method for the formation of two disulfide bridges of apamin was also examined.
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PMID:Investigation of the dimethylsulfoxide-trifluoroacetic acid oxidation system for the synthesis of cystine-containing peptides. 837 Jan 2


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