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)

An enzyme which catalyzes the deamidation of thyroliberin (TRF; less than Glu-His-Pro-NH2) has been purified 110-fold from extracts of bovine anterior pituitary by ammonium sulfate fractionation, ion exchange chromatography on DEAE-cellulose, and gel filtration. This enzyme of 76,000 molecular weight (as estimated by gel filtration) exhibits maximal activity at neutral pH (optimum pH 7.4 to 7.6) in buffers of high ionic strength supplemented with thiol-protecting agents. As indicated by the strong inhibition of the enzymatic activity by N-ethylmaleimide and Hg2+, as well as by the extreme sensitivity toward diisopropyl fluorophosphate, -SH, and -OH residues apparently represent essential functional groups of the enzyme. The stereospecific deamidation of TRF (Km = 4.1 . 10(-4) M) is inhibited competitively by TRF analogues which contain proline or by the proline containing biologically active peptides luliberin (LH-RF), oxytocin, vasopressin, angiotensin II, and Substance P. TRF analogues without proline or peptide amides without proline are ineffective. This enzyme cleaves the appropriate Pro-X bonds in luliberin, angiotensin II, pyroGlu-His-Pro-Gly-NH2, and the collagenase substrate Z-Gly-Pro-Leu-Gly-Pro. Thus, it may be characterized as a post-proline-cleaving enzyme.
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PMID:Characterization of "thyroliberin-deamidating enzyme" as a post-proline-cleaving enzyme. Partial purification and enzyme-chemical analysis of the enzyme from anterior pituitary tissue. 11 64

The NH exchange rates in aqueous media of oxytocin and 8-lysine vasopressin (LVP) have been measured by using transfer of solvent saturation method. The data are consistent with a "highly motile" dynamic equilibrium between folded and highly solvated conformations. The highly-motility limit applies to the exchange of NH hydrogens of oxytocin and LVP. Folded structures are more prevalent in oxytocin than in LVP. Partial shielding is indicated for peptide hydrogens of Asn5 and perhaps also Cys6 of oxytocin and for Cys6 of LVP. It is tentatively proposed that the folded conformation of oxytocin in aqueous media may contain a parallel beta-structure in the tocinamide ring consisting of two hydrogen bonds: one between the Tyr2 C = O and Asn5 peptide NH as originally proposed for the preferred conformation of oxytocin in dimethyl sulfoxide (D. W. Urry and R. Walter), and the second between he Cys1 C = O and the Cys6 NH. In LVP the hydrogen bond between the Tyr2 C = O and Asn5 peptide NH appears to be absent. The acylic tripeptide sequences (-Pro-X-Gly-NH2) of both hormones appear to be predominantly solvated. The second-order rate constants for acid catalyzed exchange of the primary amide hydrogens of Gln4, Asn5, and Gly9 of oxytocin are consistently greater for the trans NH than for the corresponding cis NH. This observation can be rationalized in terms of mechanisms involving protonation of either the amide oxygen, or the amide nitrogen, but with limited rotation about the C - N bond.
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PMID:Amide hydrogen exchange rates of peptides in H2O solution by 1H nuclear magnetic resonance transfer of solvent saturation method. Conformations of oxytocin and lysine vasopressin in aqueous solution. 26 22

Deamino-[8-N-methylleucine]oxytocin and deamino-[8-alpha-hydroxyisocaproic acid]oxytocin were synthesized to study the importance of hydrogen bonding between the carboxamide carbonyl of asparagine and the peptide N-H of leucine in stabilizing the biologically active conformation of oxytocin. The analogs were synthesized by coupling deaminotocinoic acid with Pro-Leu(Me)-Gly-NH2 and Pro-HyIc-Gly-NH2, respectively. (HyIc is alpha-hydroxyisocaproic acid). Deamino-[8-N-methylleucine]oxytocin was found to possess 48 +/- 7 units of uterotonic activity, 33 +/- 5 units of avian vasodepressor activity, and 3.15 +/- 1.5 units of antidiuretic activity per mg; deamino-[8-alpha-hydroxyisocaproic acid]oxytocin possessed 134 +/- 12 units of uterotonic activity, 31 +/- 3 units of avian vasodepressor activity, 9.6 +/- 3.0 units of antidiuretic activity, and 0.26 +/- 0.02 unit of pressor activity per mg. Neither of the analogs possesses the peptide N-H at residue 8 required for the formation of a hydrogen bond with the asparagine carboxamide; however, both can assume the conformation needed to evoke the characteristic biological activities of oxytocin although in lower potency. It is concluded that such a hydrogen bond does not constitute a conformational constraint that is essential for hormone action.
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PMID:Biofunctional evaluation of a hydrogen bond linking the ring and tail beta-turns of oxytocin. 29 Oct 4

1. Two enzymes acting on the linear portion of oxytocin: carboxamidopeptidase (releasing Gly . NH2) and prolyl peptidase (releasing Leu-Gly . NH2) were identified in the cytoplasmic fraction of chicken liver. 2. Carboxamidopeptidase was purified 134-fold with a 23% yield, and prolyl peptiase 71-fold with a 20% yield. The specific activity of the final preparations was 181 and 96 microU/mg protein, respectively. 3. The optimum pH for carboxamidopeptidase was 6.0--6.5 and for prolyl peptidase, 7.5. Carboxamidopeptidase activity was inhibited by Mn2+, Zn2+, Ca2+, Co2+, and stimulated by EDTA; the activity of prolyl peptidase was inhibited by Zn2+ and Mn2+. The Km value of both enzymes for oxytocin was 1.5--2.4 microM.
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PMID:Partial purification and characterization of the oxytocin-inactivating enzymes from chicken liver. 39 2

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

Effects of amiloride analogues on Na transport were studied in isolated skins of the frog Rana ridibunda. The pattern of structure-activity relationship of these compounds showed that both the -NH2 group at position 5 and Cl at position 6 of the pyrazine ring of the amiloride molecule were important for their biological activity. The paramount role of the groups at position 5 was further demonstrated by the striking properties of an analogue resulting from dimethylation of that -NH2 group. A stimulation of Na transport, opposite to the effect of amiloride itself, was observed in this instance. The increase in Na transport could already be seen at 10(-6) M and was equivalent to the measured increase in Na influx, reversible, dose-dependent, and additive to the natriferic action of oxytocin. Such characteristics resemble those reported with "external" agents like propranolol and La3+. Furthermore, mutual inhibition was observed between the stimulatory effects of this analogue and those of propranolol or La3+. These results suggest that the analogue may be considered as another "external" agent acting at sites of the external membrane distinct from those activated by cAMP but similar to the Ca sites described by Herrera and Curran (Herrera, F.C., Curran, P.F. 1963. J. Gen. Physiol. 46:999).
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PMID:Inhibitory and stimulatory effects of amiloride analogues on sodium transport in frog skin. 44 31

[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

A new analogue of oxytocin was constructed from L-tyrosyl-L-isoleucyl-L-glutaminyl-L-asparaginyl-L-lysyl-L-prolyl-L-leucyglycinamide. Reaction of this 8-peptide amide with di-p-nitrophenyl carbonate yielded a cyclic compound, in which the -CH2SSCH2-bridging portion of oxytocin formed by the oxidative linking of the two cysteine side chains was replaced by the -CH2CH2CH2CH2-group of lysine, while the epsilon-NH2 group of the same residue took the place of the alpha-CH of cysteine-1. The N-terminal amino group of oxytocin, which is not necessary for its hormonal activities, was omitted. The new analogue, referred to as [1,6-Nepsilon-carbonyl-L-lysine]oxytocin, possessed a rat uterotonic activity in vitro of 3.9 +/- 0.3 units/mg, less than 0.5 unit/mg of rat antidiuretic activity, and caused a marked tachyphylaxis in the rat pressor assay. Moreover, the analogue was a strong competitive inhibitor, with a pA2 value of 7.27 +/- 0.13 of the oxytocin induced vasodepressor response in chickens.
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PMID:A ureido group containing analogue of oxytocin comprising eight amino acid residues. 62 7

Bovine neurophysin-I (bNP-I) is the first neurophysin protein which contains histidine and possesses an acidic COOH-terminal segment for which the complete amino acid sequence is presented: NH2-Ala-Val-Leu-Asp-Leu-Asp-Val-Arg-Thr-Cys-Leu-Pro-Cys-Gly-Pro-Gly-Gly-Lys-Gly-Arg-Cys-Phe-Gly-Pro-Ser-Ile-Cys-Cys-Gly-Asp-Glu-Leu-Gly-Cys-Phe-Val-Gly-Thr-Ala-Glu-Ala-Leu-Arg- Cys-Gln-Glu-Glu-Asn-Tyr-Leu-Pro-Ser-Pro-Cys-Gln-SerGly-Gln-Lys-Pro-Cys-Gly-Ser- Gly-Gly-Arg-Cys-Ala-Ala-Ala-Gly-Ile-Cys-Cys-Ser-Pro-Asp-Gly-Cys-His-Glu-Asp-Pro-Ala-Cys-Asp-Pro-Glu-Ala-Ala-Phe-Ser-Leu-COOH. Determination of the structure was greatly facilitated by new procedures used for the isolation of bNP-I and of its tryptic peptide fragments. bNP-I isolated from freshly frozen bovine posterior pituitaries is composed of 93 residues, but some preparations contain neurophysin protein with NH2- and COOH-terminal truncated sequences. bNP-I differs from bovine neurophysin-II, the second major neurophysin of cow, in 20 residue positions, and several of the differences cannot be accounted for by single nucleotide replacements in the genes coding for these two neurophysin proteins. The results reported in this study support our earlier hypothesis that neurophysin-gene duplication preceded species divergence.
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PMID:Complete amino acid sequence of bovine neurophysin-I. A major secretory product of the posterior pituitary. 67 Jan 74

Tissue factor apoprotein and relipidated tissue factor preparations extensively hydrolyze bradykinin, Lys-bradykinin, Met-Lys-bradykinin, substance P, [Asp1, Ile5]-angiotensin II, [Asp1, Ile5]-angiotensin I, and human fibrinopeptide A while acting more slowly on [Sar1, Ile5]-angiotensin II, [Me2Gly1, Ile5]-angiotensin II, bradykinin potentiating pentapeptide from B. jararaca, luteinizing hormone-releasing hormone, melanocyte stimulating hormone-release-inhibiting factor (Pro-Leu-Gly-NH2), and oxytocin. No hydrolysis of thyrotropin-releasing factor or bradykinin potentiating nonapeptide from B. jararaca is observed. Relipidated and apoprotein tissue factor act at identical rates under the conditions of the assay. Dansylation and chromatography of tissue factor-peptide incubation mixtures further indicate that relipidated and apoprotein tissue factor also hydrolyze peptides by identical mechanisms. No fewer than six bonds are hydrolyzed in bradykinin while the angiotensins and substance P are degraded to constituent amino acids. Only the N-terminal alanine is released from fibrinopeptide A. 2-Mercaptoethanol greatly inhibits the hydrolysis of bradykinin by relipidated tissue factor.
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PMID:The hydrolysis of biologically active peptides by bovine lung tissue factor (thromboplastin). 78 91


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