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-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

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

A model for oxytocin has been previously proposed in which residues 3 and 4 occupy the corner positions in a beta turn (Urry, D. W., & Walter, R (1971) Proc. Natl. Acad. Sci. U.S.A. 68, 956). The analogue [Pro(3),Gly(4)]-oxytocin (PGO) was used in proton magnetic resonance (1H NMR) studies designed to probe the contribution of these corner positions in forming a beta turn. Comparison of various 1H NMR parameters obtained at 220 MHz for backbone amide protons of PGO with those for the corresponding protons of oxytocin suggests that, to a first approximation, these two peptides may have similar backbone conformations in )CD3)2SO. Theoretically, the L-Pro lead toGly sequence in positions 3 and 4 of PGO would allow the formation of either a type I or type II beta turn. The two coupling constants between vicinal amide and C alpha protons for Gly(4) of PGO in (CD3)2SO are compatible with a type II beta turn in which 04, the dihedral angle about the bond between the backbone C alpha and N' atoms of Gly4, is appromximately +92 degrees, but not with a type I beta turn. A survey of peptides studied in other laboratories by X-ray and/or 1H NMR with reported type II beta turns with L-Pro lead toGly or Gly lead to Gly sequences in the corner positions revealed a close correlation between chemical shifts and vicinal coupling constants for the glycl residue in the second corner position. It is suggested that this criterion can form an additional basis for the characterization of beta turns. More studies are needed to determine the particular type of beta turn manifest in the cyclic moiety of oxytocin per se, although a reasonable working hypothesis is that oxytocin, similar to PGO, has a type II beta turn.
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PMID:Conformational studies on [Pro3, Gly4]-oxytocin in dimethyl sulfoxide by 1H nuclear magnetic resonance spectroscopy: evidence for a type II beta turn in the cyclic moiety. 71 51

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

Neurophysin (Np) is generally found in close association with vasopressin and oxytocin in the hypothalamo-neurohypophyseal complex. Dog neurophysin I and II have been isolated from fresh and frozen posterior pituitaries. The proteins were characterized on the basis of disc electrophoresis, immunological properties, amino acid composition and partial sequence determination. The amino terminal sequence of dog Np I is Ala-Ala-Leu-Asp-Leu-Asp-Val-Arg-Gln-Cys-Leu-Pro-Cys-Gly-Pro-Gly-Gly-Gln-Gly-while that of dog Np-II is Ala-Met-Ser-Asp-Leu-Glu-Leu. The dog Np I appears to be metabolically less stable than Np II. Isotope experiments with [35S]cystine or 3H-labeled amino acids using a design of "in vitro pulse and in vitro chase" as well as "in vivo pulse and in vivo chase," added further confirmation of the capability of the hypothalamic neurosecretory cells to synthesize concomitantly precursors of Np and vasopressin. The radioactively labeled precursors were converted to Np-like protein and vasopressin, both of which were isolated.
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PMID:Biosynthesis of neurophysin proteins in the dog and their isolation. 83 May 36

[4-Threonine, 7-glycine]oxytocin and [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin) were synthesized by a combination of solid-phase and classical methods of peptide synthesis. A protected octapeptide was synthesized by the solid-phase method and following ammonolysis and purification 1 + 8 couplings in solution were employed to furnish the required key nonapeptide and acyl octapeptide intermediates, respectively. [7-Glycine]oxytocin was prepared from a sample of the protected nonapeptide intermediate used in the original synthesis of this peptide. [7-Glycine]oxytocin has an oxytocic potency (O) of 93 +/- 4 units/mg and an antidiuretic potency (A) of 0.0056 +/- 0.0003 units/mg. It has an O/A ratio of 16 000. [4-Threonine, 7-glycine]oxytocin has an oxytocic potency of 166 +/- 4 units/mg and an antidiuretic potency of 0.002 +/- 0.0004 units/mg. Its O/A ratio is 83 000. Threonine substitution has thus brought about a substantial enhancement in oxytocic activity and a fivefold enhancement in O/A selectivity. Hydroxy [Thr4, Gly7]oxytocin has an oxytocic potency of 218 +/- 8 units/mg and antidiuretic potency of 0.0040 +/- 0.0005 units/mg. Its O/A ratio is thus 54 500. All three 7-glycine-substituted analogues exhibit a marked sensitivity to Mg2+ on the rat uterus assay ststem and in the presence of 0.5 mM Mg2+ had oxytocic potencies in the range of 900-1000 units/mg. Should these peptides exhibit enhanced oxytocic selectivity in humans, they might offer a greater margin of safety than oxytocin in those clinical stiuations in which the latter is currently employed.
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PMID:Synthesis and some pharmacological properties of [4-threonine, 7-glycine]oxytocin, [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin), and [7-Glycine]oxytocin, peptides with high oxytocic-antidiuretic selectivity. 83 10

Vasopressin, other neurohpophyseal peptides and certain of their fragments can affect central nervous system function. Cyclo(Leu-Gly), formally derived from the C-terminal dipeptide of oxytocin, is also active in memory processes. This molecule, radioactively labeled for this study, was found to be resistant to enzymatic degradation both in vivo and in vitro. Furthermore, after its intravenous application in cat, it easily penetrated into cerebrospinal fluid. This indicates that cyclo(Leu-Gly) can readily pass from blood into the central nervous system to exert it's central pharmacological actions. Thus, labeled cyclo(Leu-Gly) is a valuable model for studying the distribution and localization of peptides which have activity in the central nervous system.
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PMID:An enzymatically stable peptide with activity in the central nervous system: its penetration through the blood-CSF barrier. 83 26

1 Thirty-three amino acids were applied separately in concentrations of 2 to 10 mM to guinea-pig uterine horns in vitro at pH 7.4. About half the acids regularly produced contractions.2 Glycine and the straight-chain L-alpha-amino acids up to norleucine were active (longer ones not tested); D-isomers were less potent or inactive in these concentrations. The omega-amino acids gamma-aminobutyric acid (GABA) and delta-aminovaleric, and the alpha,omega-diamino acids L-alpha,beta-diaminopropionic and L-alpha,gamma-diaminobutyric were active, whereas others of similar chain-length such as beta-alanine and lysine were not. The diacidic acids, glutamic and homocysteic, were more active than the amido-amino acids, glutamine and asparagine. Histidine and phenylalanine showed little or no activity.3 The use of appropriate blocking agents indicated that the responses to representative acids were not mediated by histamine, 5-hydroxytryptamine, acetylcholine, noradrenaline or by prostaglandins. Attempts to block the actions of glycine and GABA with strychnine, thebaine, picrotoxin, bicuculline or tetramethylenedisulphotetramine (TETS) were unsuccessful.4 When some of the acids that were spasmogenic at 2 to 10 mM were applied at sub-spasmogenic doses, they transiently potentiated other spasmogens such as oxytocin or acetylcholine. This effect was also shown by a mixture of amino acids at approximately the normal plasma concentrations.5 There is some similarity between the spasmogenic activities of different amino acids and their known abilities to depolarize neurones.
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PMID:Spasmogenic and potentiating actions of some amino acids on the guinea-pig myometrium. 92 51

[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

[D-alle3]-retro-D-deaminotocinamide (I), retro-L-deaminotocinamide (III) and their respective N-formyl derivatives (II and IV) were synthesized by the stepwise active ester method: deaminotocinamide was prepared by the solid-phase method. The retro-analogs of deaminotocinamide, tested at concentrations up to 10)-5)M, were found to be without activity as agonists or antagonists in the oxytocic assay. At 10(-4)M,[D-alle]-retro-D-deaminotocinamide is a weak competitive inhibitor of oxytocin. [D-alle3, Gly7]-retro-D-deaminooxytocin (V) was synthesized either by the active ester method or by a fragment condensation method employing the retro-D-RING, [D-alle3]-retro-D-deaminotocinamide, and D-tail, Boc-Gly-D-Leu-Gly, as the fragments...
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PMID:Retro analogs related to oxytocin. 96 55


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