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)

Oxytocin (OT) was synthesized employing the solid phase method. Resins made of copolymers of polystyrene-1%-crosslinked with divinylbenzene gave better yields (73-95%) of Z-Cys(Bzl)-Tyr(Bzl)-Ile-Gln-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 (I) than 2%-crosslinked resins (10--56%). Reduction of I with Na-liq.NH3 and oxidation with I2-MeOH at -40 degrees minimized dimer and polymer formation, and resulted in good yields (49--54%) of OT. The large volumes of MeOH required when several grams of I are reduced and then oxidized were rapidly evaporated in vacuo, and the residue was desalted by dissolving the peptide in a small volume of glacial acetic acid and filtering to remove the salt. OT was purified by adsorption chromatography on a silica gel column with combinations of MeOH-CHCl3 of graded polarity. Oxytocin elutes with 33% MeOH-CHCl3. After two purification steps by adsorption chromatography, the resulting OT was found to be homogeneous. The hormone was characterized chemically and found to be active biologically.
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PMID:Synthesis of oxytocin using iodine for oxidative cyclization and silica gel adsorption chromatography for purification. 42 90

[1-Deaminopenicillamine,4-threonine]oxytocin was prepared in duplicate from S-benzyl-3-mercapto-3,3-dimethylpropanoyl-Tyr(Bzl)-Ile-Thr(Bzl)-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 (I) by removal of the Bzl-protecting groups with Na-NH3, followed by cyclization of the resulting disulfhydryl compound with K3Fo(CN)6. The analogue was purified by desalting on Sephadex G-15 in 50% acetic acid and gel filtration of Sephadex G-15. The protected peptide I was synthesized (a) by the solid-phase method and (b) by a combination of solid-phase synthesis and an [8 + 1] coupling in solution. The analogue has no detectable agonist activity in rat vasopressor or isolated rat uterus assays. It has an antivasopressor pA2 of 6.67 +/- 0.09. It is a potent inhibitor of the in vitro oxytocic response to oxytocin and has a pA2 value of 7.46 +/- 0.04. (Material from the repeat synthesis has a pA2 value of 7.59 +/- 0.08.) Thus the substitution of threonine for glutamine in the antagonist [1-deaminopenicilliamine]oxytocin (pA2, 7.14 +/- 0.05) has effected a twofold increase in inhibitory potency. [1-deaminopenicillamine,4-threonine]oxytocin is one of the most potent inhibitors of oxytocin known to date.
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PMID:[1-Deaminopenicillamine,4-threonine]oxytocin, a potent inhibitor of oxytocin. 62 12

(8-Arginine)vasopressin, (8-arginine)vasotocin, oxytocin and oxypressin, the 'ring' derivatives pressinamide and tocinamide, and the extended-chain analogues Pro-Arg-Val-(8-arginine)vasopressin and (8-arginine)vasopressinoyl-Ala-Met-Ala-NH(2), were synthesized by the solid-phase method and purified by sequential gel filtration on Sephadex G-15 in 50% acetic acid and 0.2M-acetic acid. Controlled oxidation of the thiol groups of the reduced peptides obtained after deprotection with sodium in liquid ammonia gave rise to products that depended on the length of the peptide chain: (i) nonapeptides gave monomer and dimer species, (ii) hexapeptides produced mixtures containing higher polymers, and (iii) dodecapeptides gave predominantly monomer with some dimerized material. The evidence suggests that the presence of the acyclic tail tripeptide in the nonapeptide hormones induces a conformation in the preceding hexapeptide that favours the formation of an intramolecular disulphide bond. For (8-arginine)vasopressin, intramolecular disulphide-bond formation is enhanced by extension of the peptide chain from either the N- or the C-terminus. The possible significance of these studies to neurohypophysial hormone-prohormone relationships is discussed.
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PMID:Influence of the peptide-chain length on disulphide-bond formation in neurohypophysial hormones and analogues. 69 27

Using appropriate amino acid active esters (3 eq.) in presence of HOBt (1 eq.) and employing DPM protection for the thiol function of cysteine, a rapid synthesis of oxytocin in the solid phase has been accomplished. The DPM group has been removed by sodium-liquid ammonia reduction since boiling TFA is ineffective. Desaminooxytocin and 4-Thr-oxytocin have been synthesized using lesser quantities of amino acid active esters (1.5 eq.) in presence of HOBt (1 eq.), but the durations of coupling are longer. The solid-phase synthesis of desamino-oxytocin using appropriate Boc-amino acids in presence of DCCI in toluene medium has been described. Toluene does not exert any significant accelerating influence on the coupling rate as it does when active esters are employed.
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PMID:Solid-phase synthesis of oxytocin, desaminooxytocin and 4-Thr-oxytocin using active esters in presence of 1-hydroxybenzotriazole. 70 Sep 21

[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

1-Deamino-4-glu-oxytocin (1-beta-mercaptopropionic acid-4-glutamic acid - oxytocin) was synthesized by sequential reduction by sodium in liquid ammonia and oxidation by hydrogen peroxide of the octapeptide derivative, S-benzyl-beta-mercaptopropionyl-tyrosyl-isoleucyl-gamma-O-benzyl-glutamyl-asparaginyl-S-benzyl-cysteinyl-prolyl-leucyl-glycinamide. The oxidation analogue was isolated and purified by partition chromatography in two different solvent systems followed by exclusion chromatography on Sephadex G-25. It was found to possess approximately 13 I.U. of uterotonic activity, 34 I.U. of milk ejection activity, and 83 I.U. of milk ejection-like activity per milligram, measured on an isolated strip of lactating mouse mammary gland. 1-Deamino-4-Glu-oxytocin was coupled to AH-Sepharose 4B by the way of the free gamma-carboxyl group of its residue of glutamic acid. The water soluble 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride caused the coupling with approximately 70% effectiveness. The resultant peptide-agarose complex had low biological potency in the assay of milk ejection-like activity.
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PMID:Synthesis and some biological properties of 1-deamino-4-glu-oxytocin (1-beta-mercaptopropionic acid-4-glutamic acid-oxytocin) and its use in preparing a hormone-agarose complex. 112 Feb 87

[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

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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