Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carboxamidopeptidase, an enzyme which inactivates neurohypophyseal hormones, has been purified 3800-fold in an overall yield of 22% from toad skin, a neurohypophyseal hormone target organ, by (NH4)2SO4 fractionation, DEAE-Sephadex chromatography, and affinity chromatography on immobilized p-aminobenzamidine and concanavalin A-agrose. The purified enzyme is capable of inactivating both [8-arginine]vasopressin (AVP) and oxytocin by hydrolyzing the Arg8-Gly9-NH2 and the Leu8-Gly9-NH2 bonds, respectively, and can hydrolyze the ester substrates, benzoyl-L-arginine ethyl ester (BzArgOEt) and acetyl-L-trypsine ethyl ester, suggesting that the enzyme has both trypsin-like and chymotrypsin-like activities. Carboxamidopeptidase is maximally active at pH 7.5-8.5 for AVP and BzArgOEt and pH 7.0 for oxytocin. Carboxamidopeptidase is inhibited by ovoinhibitor, ovomucoid, Trasylol. lima bean trypsin inhibitor, concanavalin A, antipain, leupeptin, chymostatin, elastatinal, p-nitrophenyl p-guanidinobenzoate, and 4-methylumbelliferyl p-guanidinobenzoate but not by soybean trypsin inhibitor, alpha 1-antitrypsin, hirudin, pepstatin, bestatin, phosphoramidon, or cysteine. The enzyme is also inhibited by the serine protease inhibitor, diisopropyl phosphofluoridate (i-Pr2PF), and by the chloromethyl ketone derivatives of tosyllysine, tosylphenylalanine, and (benzyloxycarbonyl)phenylalanine, as well as by the sulfhydryl group reagent, p-(chloromercuri)benzoate (PCMB). Inhibition by PCMB is reversed by cysteine. The molecular weight determined by gel filtration in the presence of 1 MNaCl is approximately 100 000. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicates that the enzyme is composed of two identical subunits of 48 000 daltons. Each subunit consists of a heavy chain (28 000 daltons) and a light chain (19 000 daltons) joined by a disulfide bond(s). Labeling experiments using [3H]-i-Pr2PF showed that the enzyme active site is located in the heavy chain.
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PMID:Carboxamidopeptidase: purification and characterization of a neurohypophyseal hormone inactivating peptidase from toad skin. 676 14

The chemical structure of the hormone binding region of the neurophysins has been investigated by photoaffinity labeling with the photolabile tripeptide, L-[methyl-3H]Met-L-Tyr-p-azido-L-Phe amide. Photolysis of the photoaffinity tripeptide in the presence of bovine neurophysin I and II and a human neurophysin II led to approximately equal extents of covalent incorporation of radioactivity into protein. Photolabeled bovine neurophysin II was fractionated into binding site derivatized protein and nonbinding site derivatized protein by affinity chromatography, with results of amino acid and radiolabel analysis of the hormone binding site blocked protein indicating that 1 mol of tripeptide was covalently incorporated/mol of protein. Tyrosine 49 was the only protein amino acid modified in the binding site photolabeling reaction as assessed by peptide mapping of the performic acid oxidized and trypsin-digested photolabeled protein using reverse phase high performance liquid chromatography. Modification of the single neurophysin tyrosine also was found by amino acid analysis of performic acid oxidized photolabeled bovine neurophysin II. The covalent bond formed in neurophysin upon photolysis was cleaved by either exhaustive acid hydrolysis or reduction-carboxymethylation without loss of the protein amino acid residues and by performic acid oxidation with loss of both protein and tripeptide tyrosine residues. These overall data indicate that tyrosine 49 is the probable site for specific covalent attachment of the photoaffinity tripeptide. Assuming that the tripeptide binding site is the high affinity hormone binding site reported for the neurophysins, this conclusion argues that tyrosine 49 is close to or within this site.
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PMID:Photoaffinity labeling of the hormone binding site of neurophysin. 706 22

Vasopressor and depressor properties of angiotensins (ANG) were characterized in the anesthetized, adult female chicken Gallus gallus. [Asp1,Val5,Ser9]ANG I and [Asp1,Val5]ANG II (native fowl angiotensins) increased blood pressure, and removal or replacement of the amino acid in position 1 decreased pressor potency. The pressor effect of [Asp1,Val5]ANG II was inhibited nearly completely with [Sar1,Ile8]ANG II (5 micrograms.kg-1.min-1) and partially with [Sar1,Thr8]ANG II, [Ile8]ANG III, and [Ile8]ANG I. Phenoxybenzamine, reserpine, or 6-hydroxydopamine reduced the pressor action to one-third. After administration of these compounds [Asp1,Val5]ANG II caused biphasic responses, a depressor followed by a small pressor response. [Sar1,Ile8]ANG II completely, and meclofenamate partially, blocked the depressor response, whereas propranolol, methysergide, vasopressin antagonists, or atropine did not. These results suggest that in fowl 1) the first (Asp) and eighth (Phe) amino acids are important for receptor binding and action, 2) vasopressor action of angiotensin may be primarily caused by release of catecholamines, and 3) angiotensin may exert depressor action possibly by acting directly on the vascular smooth muscle.
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PMID:Vasopressor and depressor actions of angiotensin in the anesthetized fowl. 706 93

Bovine neurophysin II was partially digested by chymotrypsin and by chymotrypsin followed by carboxy-peptidase B to produce large fragments collectively representing deletions of residues 1-5 and 91-95. All such fragments were capable of binding peptides to the principal hormone-binding site of neurophysin with normal or near-normal affinity, indicating that residues 1-5 and 91-95 do not directly participate in binding. In addition, preliminary results with thermolysin-derived fragments suggested that residue 6 does not participate in peptide binding. During the course of chymotrypsin studies, it was demonstrated that bovine neurophysin II behaves as a transient competitive inhibitor of chymotrypsin; for neurophysin-peptide complexes, Ki congruent to 8 x 10(-6) M. This inhibition is dependent on neurophysin conformation and is relieved by the anomalous preferential splitting by chymotrypsin of Arg-Arg and Phe-Pro bonds near the carboxyl terminus of neurophysin II. It is suggested that this phenomenon might reflect the interaction of neurophysin II with a chymotrypsin-related enzyme in the pituitary. One approach used in the study of binding properties of proteolytically modified neurophysin was affinity chromatography; the preparation and properties of a conveniently prepared affinity column for neurophysin are described.
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PMID:Partial digestion of neurophysins with proteolytic enzymes: unusual interactions between bovine neurophysin II and chymotrypsin. 707 53

The reciprocal modulation of neurophysin self-association and noncovalent peptide--protein interaction between neurophysin and the hormones oxytocin and vasopressin has been assessed by quantitative affinity chromatography. Competitive elutions of radiolabeled bovine neurophysin II (NPII) from the affinity matrices Met-Tyr-Phe-omega-(amino-hexyl)- [and (aminobutyl)-] agarose were performed with increasing concentrations of either of the soluble ligands oxytocin or lysine-vasopressin. Also, the dependence of NPII retardation by the same adsorbents on the concentration of applied protein was investigated in the absence of soluble ligand. The affinity constant of NPII for the immobilized peptide increased markedly with increasing amounts of applied protein and with the addition of small amounts of soluble ligand, the latter being more pronounced at higher protein concentrations. The affinity constant of the protein for the soluble ligand showed a smaller increase. The variation of l/(V - V0) (where V = the NPII elution volume and V0 = the elution volume of noninteracting control protein) with soluble ligand concentration was linear except near [ligand] = 0. The quantitative affinity chromatographic results on the tripeptidyl affinity columns are consistent with the view that NPII exists in a monomer in equilibrium dimer equilibrium, with the dimer exhibiting a stronger interaction with both neuropeptide and tripeptide analogues. The data also indicate that the self-associated protein dimer itself exhibits cooperativity, that is, stronger binding of the immobilized ligand at one site when a second site is occupied with a molecule of the soluble ligand than when no soluble ligand is bound. The deduction from the above of ligand-induced dimerization is evident also in the increased retardation of NPII on neurophysin--Sepharose when the eluting buffer contains soluble peptide hormone.
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PMID:Interdependence of neurophysin self-association and neuropeptide hormone binding as expressed by quantitative affinity chromatography. 708 36

Limited tryptic fragmentation of disulfide-intact bovine neurophysins I and II (NP-I and -II, respectively) has been found to cause selective disruption of both hormone binding and neurophysin self-association. Loss of binding interactions, measured as a loss of ability to stimulate retardation of 125I-labeled neurophysin on Met-Tyr-Phe-amino-butylaminoagarose, is complete within 3 h at 37 degrees C. Reverse-phase high-performance liquid chromatography (HPLC) analysis of tryptic digests of neurophysin I allows detection of two major protein products and the peptide fragment 1-8. Release of the latter N-terminal piece occurs at about the same rate as loss of binding interactions. Reverse-phase HPLC elution behavior before and after performic acid oxidation and amino acid composition of the protein products led to their identification as NP-I-(9-93) (the 9-93 sequence) and [des-19,20]NP-I-(9-93) (the 9-93 sequence with the dipeptide 19-20 missing) for the more rapidly and more slowly formed species, respectively. NP-I-(9-93), unlike intact neurophysin I, is not retarded strongly by either Met-Tyr-Phe-amino-butylaminoagarose or neurophysin II-Sepharose. In contrast, both NP-I-(9-93) and [des-19,20]NP-I-(9-93) are equally as effective as intact NP-I in binding neurophysin I antibodies. The role of amino-terminal residues in promoting hormone binding, self-association, and antigenic recognition interactions is considered.
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PMID:Effects of limited tryptic proteolysis of bovine neurophysins on molecular properties of hormone binding, self-association, and antigenicity. 715 May 67

The synthesis of three reactive analogues of [1,6-alpha-aminosuberic acid, 8-arginine]-vasopressin ([Asu1,6,Arg8]vasopressin) is described. Two peptide hormone analogues contain in the p-position of Phe2 the azido or 3-(3-methyl-3-diazirinyl)propanoylamino residue, which can be converted by photoactivation into nitrenes and carbenes, respectively. The third derivative contains the chemically reactive (bromoacetyl)amino group in the same position. The analogues are prepared via the precursor [Asu1,6,Phe(pNH2)2,Arg8]vasopressin, which is obtained by peptide synthesis in solution. Modifications of the p-amino group of Phe(pNH2) give the reactive analogues. The analogue containing p-azidophenylalanine in Pos. 2 shows a similar high binding affinity for the antidiuretic receptor in bovine kidney as vasopressin. By iodination of the Phe(pNH2) residue, followed by catalytic dehalogenation, the 2-(p-amino-phenylalanine) analogue is labelled with tritium at a specific radioactivity of 16 Ci/mmol. It can be converted into the tritium-labelled 2-(p-azidophenylalanine) analogue without loss of binding affinity for vasopressin receptors.
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PMID:[Tritium-labeled reactive analogs of [1,6-alpha-aminosuberic acid, 8-arginine] vasopressin (deamino-dicarba-[8-arginine] vasopressin. synthesis and properties]. 716 Aug 23

The synthesis and biological activities of arginine-vasopressin analogues are described, where p-azido-L-phenylalanine [Phe(pN3)] or p-(bromoacetylamino)-L-phenylalanine [Phe-(pNHCOCH2Br)] replace Tyr2 or Phe3. The hormone analogues are prepared via precursors containing p-aminophenylalanine [Phe(pNH2)] in position 2 or 3. During peptide synthesis the p-amino group of [Phe(pNH2)] is protected by the tert-butyloxycarbonyl or the benzyloxycarbonyl group, the side chains of cysteine and arginine by the acetamidomethyl residue and the tosyl group, respectively. The amino and guanidino protecting groups are removed from the nonapeptides by trifluoromethanesulfonic acid yielding the S-protected derivatives which are cyclized by means of iodine. The ring closure by disulfide formation is confirmed by Edman degradation, CD and 1H-NMR spectroscopy. Modification at the p- and alpha-amino groups result in [Phe(pN3)2]-vasopressin, [Phe(pNHCOCH2Br)2]vasopressin, Nalpha-dansyl-[Phe(pN3)2]vasopressin, [Phe2,Phe-(pN3)3]vasopressin and [Phe2,Phe(pNHCOCH2-Br)3]vasopressin. The analogues modified only in position 2, [Phe(pN3)2]vasopressin stimulate the adenylate cyclase derived from bovine kidney inner medulla to similar maximal velocities as arginine vasopressin and show high apparent affinities for enzyme activation. The Nalpha-dansyl derivative and the analogues with reactive groups in position 3 have reduced maximal velocities and apparent affinities for vasopressin-sensitive adenylate cyclase. These results suggest that especially the derivatives with reactive groups in position 2 are useful for the labelling of vasopressin receptors in plasma membranes and for studies of covalent hormone-receptor complexes.
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PMID:Synthesis and biological activities of arginine-vasopressin analogues with reactive groups. 735 40

Recent investigations on marsupial neurohypophysial hormones have revealed that species belonging to the Australian family Macropodidae and the American family Didelphidae have, apart from an oxytocin-like hormone, two vasopressin-like peptides which can be separated either by ion-exchange chromatography or chromatoelectrophoresis. The major pressor hormone of two Australian species, the red kangaroo (Macropus rufus) and the tammar (Macropus eugenii), has been identified as lysine vasopressin by its amino acid sequence anda its pharmacological properties. We report here that the minor pressor hormone, which chromatographs on Amberlite CG-50 like arginine vasopressin, differs from it in sequence only at position 2 where phenylalanine replaces the tyrosine of arginine vasopressin.
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PMID:Phenypressin (Phe2-Arg8-vasopressin), a new neurohypophysial peptide found in marsupials. 743 83

The effects of beta-endorphin and various enkephalins on protein synthesis in eukaryotic cell-free systems have been examined. Beta-Endorphin, Leu-enkephalin, and Met-enkephalin inhibit the incorporation of radioactive leucine into globin in the presence of reticulocyte poly(A)+ RNA and of radioactive phenylalanine into polyphenylalanine in the presence of poly(U); however, the poly(U)-dependent synthesis of polyphenylalanine from Phe-tRNA is not inhibited. the aminoacylation of tRNAPhe is markedly inhibited by enkephalin, indicating that the sensitive component is Phe-tRNA synthetase. Other aminoacyl-tRNA synthetases are not significantly affected. The interaction between enkephalin and Phe-tRNA synthetase is reversible; activity is restored by dialysis of enzyme-enkephalin reaction mixtures. Morphine, vasopressin and analogues of vasopressin, and enkephalin analogues such as [D-Ala2,D-Leu5]enkephalin and [D-Ala2,Met]enkephalinamide have no effect on translation. The results suggest that the effects on protein synthesis are probably not related to opiate effects.
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PMID:The effects of beta-endorphin and enkephalins on protein biosynthesis in a eukaryotic cell-free system. Inhibition of phenylalanyl-tRNA synthetase. 744 May 77


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