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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental conditions and parameters involved in high performance liquid chromatography (HPLC) separations of the peptide hormone oxytocin and seven of its diastereoisomers, namely [1-hemi-D-cystine]-, [2-D-tyrosine]-, [4-D-glutamine]-, [5-D-asparagine]-, [6-hemi-D-cystine-], [7-D-proline]-, and [8-D-leucine]-oxytocin, on reverse phase columns were investigated. The effects of solvent, pH, and salt concentration were studied. Using the solvent systems 10% tetrahydrofuran-ammonium acetate buffer or 18% acetonitrile-ammonium acetate buffer and the muBondapak C18 support, oxytocin was separated from each of its diastereoisomers under all conditions studied, but the order of elution of diastereoisomers was highly dependent on solvent and to a lesser extent on pH. Separations of the hormone and its diastereoisomers on reverse phase HPLC and on classical partition chromatography on Sephadex G-25 were compared. The results are discussed in terms of the interactions of the solute with the reverse phase column and the solvent system. Implications of these findings in terms of the different solution conformations of the peptides are discussed.
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PMID:The separation of peptide hormone diastereoisomers by reverse phase high pressure liquid chromatography. Factors affecting separation of oxytocin and its diastereoisomers--structural implications. 3 28

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

Synthesis and biological properties of [5-(N4,N4-dimethylasparagine)]oxytocin are reported. In this analogue, the hydrogens of the primary carboxamide moiety in the side chain of the asparagine residue in position 5 of the posterior pituitary hormone oxytocin have been replaced by two methyl groups. The protected nonapeptide intermediate was prepared by a stepwise procedure using solution techniques. The analogue possesses 4.60 +/- 0.03 units/mg (mean +/- SEM) uterotonic activity on the isolated rat uterine horn and 9.14 +/- 0.03 units/mg of avian vasodepressor activity. Moreover, it displays an identical intrinsic activity in the in vitro rat uterotonic assay as oxytocin, when tested in the presence of either 0.5 mM Ca2+ (standard assay conditions) or at reduced levels of Ca2+ (0.3, 0.15, and 0.05 mM). This result is significant in view of the proposed biologically active model of oxytocin, in which the side chain of the 5 position residue was assigned to contain an "active element" responsible for the intrinsic activity of the hormone when bound to the uterine receptor.
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PMID:Active-site studies of neurohypophyseal hormones: synthesis and pharmacological properties of [5-(N4,N4-dimethylasparagine)]oxytocin. 44 89

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

The solution conformation of a retro-D analogue of tocinamide H-D-Cys-D-Asn-D-Gln-D-aIle-D-Tyr-NHCH2CH2S was examined using proton magnetic resonance and circular dichroism spectroscopy. The observations support major contributions to the conformational distribution from structures with a type I beta turn in the sequence D-Asp-D-Gln-D-aIle-D-Tyr. This is topologically similar to the beta turn proposed for oxytocin, L-Tyr-L-Ile-L-Gln-L-Asn, but with the polarity of the CONH groups reversed along the chain; the peptide is, however, hormonally inert. In conjuction with nuclear magnetic resonance data, the circular dichroism spectra are interpreted to indicate that the region of the peptide ring near the disulfide occurs in at least two different conformations. One of the side-chain carboxamides, probably that of asparagine, appears to be intramolecularly associated rather than freely exposed to solvent.
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PMID:Solution conformation of a retro-D analogue of tocinamide. 95 44

To identify and characterize oxytocin receptors, a 125I-labeled photoreactive oxytocin antagonist was synthesized. The specific oxytocin antagonist [1-(beta-mercapto-beta,beta- cyclopentamethylenepropionic acid), 2-O-methyltyrosine,4-threonine,8- ornithine,9-tyrosylamide]oxytocin ([Mca,Tyr(O-Me)2,Thr4,Orn8,Tyr9-NH2]oxytocin) described by Elands et al. (Elands, J., Barberis, C., Jard, S., Tribollet, E., Dreifuss, J.-J., Bankowski, K., Manning, M., and Sawyer, W. H. (1987) Eur. J. Pharmacol. 147, 192-207) bound to the guinea pig uterine oxytocin receptor with high affinity (apparent Kd = 0.74 nM). The introduction of a 4-azidophenylamidino group at Orn8 resulted in the photoreactive ligand [Mca1,Tyr(O-Me)2,Thr4,Orn(4-azidophenylamidino)8,Tyr9- NH2]oxytocin, which retained the high binding affinity (Kd = 0.69 nM) of the parent compound. The photoreactive antagonist monoiodinated at Tyr9 had approximately double (Kd = 0.39 nM) the affinity of the photoreactive antagonist and several times that of oxytocin (Kd = 2.6 nM) for the guinea pig uterine oxytocin receptor. In photo-affinity labeling experiments using myometrial membranes obtained from guinea pigs during late pregnancy, the 125I-labeled photoreactive antagonist specifically labeled a protein with an apparent molecular mass of between 68 and 80 kDa: the labeling of this protein was completely suppressed by a 100-fold molar excess of oxytocin and oxytocin receptor-specific agonists, but not by vasopressin analogues specific for V1 or V2 receptors or by other peptide hormones. The ability of oxytocin to suppress labeling was decreased in the presence of guanosine 5'-O-(thiotriphosphate) or in the absence of Mn2+. Digestion of the photolabeled oxytocin receptor with endoglycosidase F gave rise to a protein with an apparent molecular mass of 38 +/- 2 kDa. The endoglycosidase F effect and the lack of endoglycosidase H action show that the myometrial oxytocin receptor is highly glycosylated with asparagine-linked complex oligosaccharide chains. Our results suggest that the radioiodinated photoreactive oxytocin antagonist could be a helpful tool in the isolation and further characterization of the oxytocin receptor.
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PMID:Identification and enzymatic deglycosylation of the myometrial oxytocin receptor using a radioiodinated photoreactive antagonist. 165 65

1. The interaction between lipid monolayers spread on the surface of water and oxytocin, [8-arginine]-vasotocin and [1-asparagine-5-valine]-angiotensin II in the subphase was investigated in a Langmuir surface trough by studying the changes in pressure produced on injection of various quantities of the polypeptide solution under the film. 2. The effect of 2m- and 4m-urea on the character of the adsorption is reported. 3. Structures for the adsorbed films formed in this way are suggested. 4. If the lipid monolayer is taken as a suitable model of cell membranes, then it may be supposed that the effect of such structures forming in cell membranes would be to provide effective ;pores' to facilitate the movement of water and other small molecules across the membrane.
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PMID:Interaction of polypeptide hormones with lipid monolayers. 429 25

This paper describes the synthesis and biological activity of [5-L-asparagine-alpha,beta,beta-d(3)]-deamino-oxytocin. The model peptide S-benzyl-beta-mercaptopropionyl-L- asparaginyl-alpha,beta,beta-d(3)-glycinamide was also prepared to observe the effect of the conditions of peptide synthesis on the deuterium content. It was found that normal synthetic procedures could be used without a significant loss in the deuterium content.The [5-L-asparagine-alpha,beta,beta-d(3)]-deamino-oxytocin had, within experimental error, the same avian vasodepressor and oxytocic activities as deamino-oxytocin itself.
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PMID:Deuterated oxytocins: the synthesis and biological properties of a crystalline analog of deamino-oxytocin deuterated in the 5-asparagine position. 526 9

The secondary structure of the cyclic moiety of oxytocin and deamino-oxytocin has been determined by nuclear magnetic resonance spectroscopy (220 MHz). Oxytocin, in a dimethylsulfoxide-methanol mixture, contains a beta-turn involving the sequence -L-tyrosyl-L-isoleucyl-L-glutaminyl-L-asparaginyl-. Deamino-oxytocin, in addition to the beta-turn, contains a hydrogen bond involving the amide hydrogen of the tyrosine residue and the peptide carbonyl group of the asparagine residue, resulting in an antiparallel beta-type conformation for the ring component. An initial attempt has been made to relate conformational features of the hormonal peptides to their biological activity.
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PMID:Secondary structure of the cyclic moiety of the peptide hormone oxytocin and its deamino analog. 527 89

A conformation of the neurohypophyseal hormone oxytocin in solution is proposed. The structure possesses, in addition to the beta-turn comprised of the sequence -L-tyrosyl-L-isoleucyl-L-glutaminyl-L-asparaginyl- in the ring component of the hormonal molecule, a second beta-turn involving the C-terminal oxytocin sequence, -L-cysteinyl-L-prolyl-L-leucylglycinamide. The resulting oxytocin structure places the bulky side chains of the leucine and isoleucine residues, as well as the cyclic moiety of the proline residue, at corners of the two beta-turns. A critical role is played by the asparagine residue: its peptide N-H participates in the formation of the hydrogen-bonded cyclic structure of the beta-turn in the ring component of oxytocin and its peptide C=O can be hydrogen-bonded to the N-H of tyrosine, while its side chain C=O stabilizes the second beta-turn by forming a hydrogen bond with the N-H of the leucine residue, which is part of the end peptide of the second beta-turn. This conformational assignment of oxytocin is consistent with hydrogen-deuterium exchange studies, with plots of temperature dependence of peptide proton chemical shifts, and with the coupling constants for the NH-CH dihedral angles.
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PMID:Proposed conformation of oxytocin in solution. 528 May 29


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