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)

The reaction products of plasma enzyme degradation of TRH were identified by thin layer chromatography. The enzyme in normal rat plasma yields proline and pGlu-His as major reaction products. High concentrations of proline decrease peptide cleavage, resulting in greater amounts of acid TRH. The apparent Km of the enzyme is 4.1 X 10(-6) M. LHRH and neurotensin are competitive inhibitors with Ki of 5 X 10(-6) M and 1.5 X 10(-5) M, respectively. Somatostatin, MIF, oxytocin, arg-vasopressin, arg-vasotocin, neurophysin II and glucagon do not compete; and pGlu-His-Pro-OH, Glu-His-Pro-OH, pGlu-His, His-Pro-NH2, and Pro-NH2 do not affect enzyme activity. These data suggest that the substrated requires pGlu and a terminal or internal amide to complex with the enzyme. The enzyme is markedly inhibited by Cu++, Bal, benzamadine, p-(chloromercuri)-benzoic acid, moderately affected by EDTA and puromycin, and unaffected by mercaptoethanol. TSH does not affect enzyme activity while LH inhibits it moderately at high concentrations (300-600 pg/ml).
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PMID:Characteristics of the plasma TRH-degrading enzyme. 81 19

[7-Thiazolidine-4-carboxylic acid)]oxytocin and [1-beta-mercaptopropionic acid,7-(thiazolidine-4-carboxylic acid)]oxytocin have been synthesized by a solid-phase method. Alpha-N-tert-Butoxycarbonyl- and S-ethylcarbamoyl-protecting groups were employed. The dipeptide Boc-Cys(Ec)-thiazolidine-4-carboxylic acid as well as individual residues was coupled to a H-Gly-dehydroalanine-resin with dicyclohexylcarbodiimide in the presence of 1-hydroxybenzotriazole. The appropriate protected polypeptide intermediates were cleaved from the resin by acidolysis, deprotected in NH3, and oxidized to the cyclic disulfide analogues with ICH2CH2I. Purification was effected by partition chromatography and gel filtration. Relative to oxytocin and [1-beta-mercaptopropionic acid]oxytocin, these analogues exhibit greatly enhanced oxytocic and avian vasodepressor potencies and unchanged rat pressor potencies.
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PMID:Synthesis and some pharmacological properties of oxytocin analogues having L-thiazolidine-4-carboxylic acid in position 7. 94 Jan 6

Homogeneous porcine neurophysin III has been obtained from slightly contaminated neurophysin material by rechromatography on diethylaminoethyl-cellulose. The purified protein binds both oxytocin and lysine vasopressin. Gel filtration on a calibrated column of Sephadex G-75 gives an estimate of the molecular weight of 10,000. Amino acid analyses establish the composition Lyla8, 1/2Cys14, Val2, Met1, Ile2, Leu7, Tyr1, Phe3. The total number of amino acid residues is 95. This composition exceeds that of porcine neurophysin-I by 1 alanine and 2 arginine residues. It has an NH2-terminal alanine and the COOH-terminal sequence- Arg-Arg-Ala. Results of peptide maps, the amino acid composition of tryptic peptides, and the sequences of two small tryptic peptides suggest that porcine neurophysin III contains the entire molecule of porcine neurophysin I plus a tripeptide -Arg-Arg-Ala connected the COOH terminus. It is threfore possible that porcine neurophysin I may have been derived from porcine neurophysin III by the proteolytic removal of the last 3 or 4 amino acid residues from the COOH terminus, and that the porcine hypothalamic tissue synthesizes only two neurophysins, II and III.
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PMID:Characterization of porcine neurophysin. III. Its resemblance and possible relationship to porcine neurophysin I. 94 86

Neurohypophyseal hormones and several of their analogs, as well as N-terminal and C-terminal fragments, have been studied for their ability to attenuate puromycin-induced amnesia in mice. [8-Lysine]vasopressin, [8-arginine]vasopressin, and the analogs des-9-glycinamide-[8-lysine]vasopressin, [1-beta-mercaptopropionic acid, 8-lysine]vasopressin, [1,6-aminosuberic acid, 8-lysine]vasopressin, [4-leucine, 8-lysine]vasopressin, glycyl-glycyl-glycyl-[8-lysine]vasopressin, [1-beta-mercaptopropionic acid, 8-D-arginine]vasopressin, and [1,6-aminosuberic acid, 8-arginine]vasopressin are active. [8-Arginine]oxytocin as well as oxytocin and all of its other analogs tested are inactive with the striking exception of glycyl-glycyl-glycyl-oxytocin. The structural aspects of the neurohypophyseal hormones which appear to be important for significant activity in memory consolidation include the combination of a cyclic moiety containing the Tyr and Phe residues along with a basic residue in position 8. Another series of active compounds comprises C-terminal neurohypophyseal peptides and analogs thereof, including the naturally occurring Pro-Leu-Gly-NH2 and, most surprisingly, Leu-Gly-NH2, as well as its derivatives D-Leu-Gly-NH2 and the diketopiperazine, cyclo(-Leu-Gly-).
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PMID:Neurohypophyseal hormones, analogs, and fragments: their effect on puromycin-induced amnesia. 106 98

Arginine-vasopressin and oxytocin, both 14C-labeled in the glycine residue, are enzymatically inactivated by rat kidney supernatant. Production of radioactive metabolites of each hormone was followed as a function of time. Both oxytocin and vasopressin are degraded by an enzyme which cleaves their Pro-X bonds, to release Leu-Gly-NH2 from oxytocin and Arg-Gly-NH2 from vasopressin. In addition, oxytocin alone is degraded rapidly by a chymotrypsin-like enzyme which directly releases Gly-NH2 from the hormone. The direct release of Gly-NH2 from vasopressin in the homogenate is of minor importance, but there occurs a transient formation of an uncharacterized fragment in significant amounts. The data are interpreted to indicate that the difference in the overall mechanism of inactivation of the two hormones by the rat kidney extract is a result of the high level of the enzymic activity which releases Gly-NH2 directly from oxytocin, compared to the low level of activity releasing Gly-NH2 directly from the antidiuretic hormone. This allows, in the case of arginine vasopressin, a greater expression of the activity of enzyme(s) giving rise to uncharacterized fragment(s) and of the Pro-X cleaving enzyme.
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PMID:Differences in the enzymatic inactivation of arginine vasopressin and oxytocin by rat kidney homogenate. 111 88

[1-Beta-mercapto-beta,beta-pentamethylenepropionic acid]oxytocin was prepared from beta-Mpa(beta-(CH2)5)(Bzl)-Tyr(Bzl)-Ile-Gln-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 by removal of the Bzl-protecting groups with Na-NH3 followed by cyclization of the resulting disulfhydryl compound with K3Fe(CN)6.The analog was purified by desalting on Sephadex G-15 in 50% HOAc and gel filtration on Sephadex G-25 and LH-20. The protected intermediate above was synthesized from Z-Cys(Bzl)-Pro-Leu-Gly-NH2 by the stepwose p-nitrophenyl ester method using Nalpha-Boc protection at the penta-, hexa-, and octapeptide stages. The analog was found to be a potent inhibitor of the oxytocic and avian vasodepressor effects of oxytocin (pA2 values of 7.43 and 8.30, respectively) but was only a weak inhibitor of the rat pressor effect of 8-lysine-vasopressin. The rat antipressor potency of [1-deaminopenicillamine]oxytocin was also determined in this study: pA2 = 6.27. Of the alkyl-substituted 1-position analogs of oxytocin studied so far, [1-beta-mercapto-beta,beta-pentamethylenepropionic acid]oxytocin is the most potent antioxytocic agent.
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PMID:[1-Beta-mercapto-beta,beta-pentamethylenepropionic acid]oxytocin, a potent inhibitor of oxytocin. 113 19

Reaction of tetranitromethane with the lone tyrosine residue of bovine neurophysin I and II, tyrosine-49, gave nitro derivatives of these proteins which were obtained in a highly purified form by preparative electrophoresis. Equilibrium dialysis experiments indicated clearly that oxytocin binding remained essentially unaffected by the chemical modification of tyrosine-49. However, in the case of (8-lysine)vasopressin, the nitrated protein was found to bind only 1 hormone molecule in contrast to the 2 vasopressin molecules bound by the native protein. Ultraviolet absorption difference spectroscopy measurements between 250 nm and 300 nm indicated that upon binding of (2-phenylalanine, 8-lysine)vasopressin, tyrosine-49 of native neurophysin undergoes a change of microenvironment from less to more polar surroundings. Studies of the nitrotyrosyl-49 chromophore of neurophysin by ab sorption spectroscopy in the absence and presence of oxytocin or (8-lysine)vasopressin confirmed this finding. Since dimethylsulfoxide solvent perturbation studies suggested that in the Cys(Me)-Phe-Ile-NH2-neurophysin I complex, tyrosine-49 is more exposed to solvent than in neurophysin I alone, it is concluded that this residue is unmasked by conformational changes upon complex formation.
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PMID:Interactions of bovine neurophysins with neurohypophyseal hormones. On the role of tyrosine-49. 115 Jun 56

For the synthesis of [1-L-penicillamine,4-L-leucine]oxytocin (2), Z-Tyr(Bzl)-Ile-Leu-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 was treated with anhydrous HBr, and the resulting partially deprotected octapeptide was coupled with Z-penicillamine(Bzl) in a condensation reaction mediated by dicyclohexylcarbodiimide and 1-hydroxybenzotriazole. The protected nonapeptide Z-penicillamine(Bzl)-Tyr-Ile-Leu-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 was treated with Na in NH3 and the resulting disulfhydryl compound was subjected to oxidative cyclization in H2O-CH3OH with ICH2CH2I, Purification of 2 was effected by partition chromatography and gel filtration. The analog possesses antioxytocic and antiavian vasodepressor pA2 values of 6.77 and 7.21, respectively, and has no antipressor or anti-ADH activity. Its biological activity spectrum is qualitatively identical with that of [1-penicillamine]oxytocin. In contrast to the marked natriuretic-diuretic and anti-antidiuretic activity of [Leu4]oxytocin, 2 exhibits none of these effects on the rat kidney.
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PMID:Synthesis and pharmacological properties of [1-L-penicillamine,4-L-leucine]oxytocin. 115 79

[4-Phenylalanine]oxytocin was prepared from Z-Cys(Bzl)-Tyr(Bzl)-Ile-Phe-Asn-Cys(Bzl)-Pro-Leu-Gly-NG2 (4) by deprotection with Na in NH3 followed by cyclization of the resulting disulfhydryl compound with ICH2CH2I. The protected peptide 4 was prepared from Boc-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 by the stepwise solution method. Coupling was effected by a modification of the dicyclohexylcarbodiimide-1-hydroxybenzotriazole preactivation method wherein the precipitate of dicyclohexylurea is removed by filtration prior to mixing of the amino and carboxyl components. The analog was found to be an effective inhibitor of the antidiuretic (ADH) response to exogenous arginine-vasopressin. It produced marked diuresis in the anti-ADH assay at approximately the same dose level as does [Leu4]oxytocin but, in contrast to [Leu4]oxytocin, showed natriuretic activity only at relatively high dose levels. In addition, [Phe4]oxytocin exhibited 0.15% of the oxytocic potency of oxytocin, weak antiavian vasodepressor activity (pA2 = 6.93), and no measurable rat pressor activity.
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PMID:(4-Phenylalanine)oxytocin, an inhibitor of the antidiuretic effect of 8-arginine-vasopressin. 115 80

[1-Beta-Mercaptopropionic acid,2-(3,5-dibromo-L-tyrosine)]oxytocin was synthesized from a protected polypeptide intermediate that had been prepared by the condensation of S-ethylcarbamoyl-beta-mercaptopropionyl-3,5-dibromotyrosine with H-Ile-Gln-Asn-Cys(Ec)-Pro-Leu-Gly-NH2, using dicyclohexylcarbodiimide in dimethylformamide. The ethylcarbamoyl (Ec) protecting groups were removed by refluxing NH3, and the resulting disulfhydryl peptide was oxidatively cyclized to the corresponding disulfide by ICH2CH2I. Purification of the analog was effected by partition chromatography and gel filtration. The analog possesses antioxytocic (pA2 = 7.05) and antiavian vasodepressor (pA2 = 7.44) activities but has neither agonist nor antagonist activity in the rat pressor assay.
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PMID:(1-Beta-mercaptopropionic acid, 2-(3,5-dibromo-L-tyrosine))oxytocin, a potent inhibitor of oxytocin. 115 88


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