Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthesis and biological activities of arginine-vasopressin analogues are described, where p-azido-L-phenylalanine [Phe(pN3)] or p-(bromoacetylamino)-L-phenylalanine [Phe-(pNHCOCH2Br)] replace Tyr2 or Phe3. The hormone analogues are prepared via precursors containing p-aminophenylalanine [Phe(pNH2)] in position 2 or 3. During peptide synthesis the p-amino group of [Phe(pNH2)] is protected by the tert-butyloxycarbonyl or the benzyloxycarbonyl group, the side chains of cysteine and arginine by the acetamidomethyl residue and the tosyl group, respectively. The amino and guanidino protecting groups are removed from the nonapeptides by trifluoromethanesulfonic acid yielding the S-protected derivatives which are cyclized by means of iodine. The ring closure by disulfide formation is confirmed by Edman degradation, CD and 1H-NMR spectroscopy. Modification at the p- and alpha-amino groups result in [Phe(pN3)2]-vasopressin, [Phe(pNHCOCH2Br)2]vasopressin, Nalpha-dansyl-[Phe(pN3)2]vasopressin, [Phe2,Phe-(pN3)3]vasopressin and [Phe2,Phe(pNHCOCH2-Br)3]vasopressin. The analogues modified only in position 2, [Phe(pN3)2]vasopressin stimulate the adenylate cyclase derived from bovine kidney inner medulla to similar maximal velocities as arginine vasopressin and show high apparent affinities for enzyme activation. The Nalpha-dansyl derivative and the analogues with reactive groups in position 3 have reduced maximal velocities and apparent affinities for vasopressin-sensitive adenylate cyclase. These results suggest that especially the derivatives with reactive groups in position 2 are useful for the labelling of vasopressin receptors in plasma membranes and for studies of covalent hormone-receptor complexes.
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PMID:Synthesis and biological activities of arginine-vasopressin analogues with reactive groups. 735 40

The primary structure of an elephant neurophysin, homologous to vasopressin-associated neurophysins, is reported. The protein contains a Tyr for Asn substitution at position 75, a position in direct contact with residues 77 and 78 of the monomer-monomer interface. This Tyr residue therefore serves as a potential reporter of the path involved in the long-range linkage between peptide binding and dimerization in this system. NMR studies of the protein in unliganded and liganded states demonstrated normal dimerization properties and the expected increase in dimerization associated with binding peptide. In keeping with an elevated pKa of 11.1 assigned to Tyr-75 by UV spectrophotometric titration, the NMR signals from the 3,5 and 2,6 ring protons of Tyr-75 were shifted 0.3 and 0.2 ppm upfield, respectively, relative to their positions in small peptides, indicating significant shielding and/or hydrogen bonding. The Tyr-75 ring proton signals narrowed slightly, with no discernible change in chemical shift, on conversion from dimer to monomer in the unliganded state. Ring protons of Tyr-49, distant from the monomer-monomer interface, but adjacent to the peptide-binding site, were markedly perturbed by dimerization, in accord with their behavior in bovine neurophysins. The results suggest that the secondary and tertiary structure of the region 75-78 is largely unchanged by dimerization, and argue against an important role for this region in dimerization-mediated conformational changes that alter the binding site in the unliganded state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amino acid sequence and properties of vasopressin-associated elephant neurophysin. 782 4

Two analogues of the antidiuretic drug [1-desamino,8-D-arginine]vasopressin (DDAVP), which have a glycosylated serine at position 4, have been prepared by Fmoc solid phase peptide synthesis. The glycosylated analogues had significantly higher bioavailabilities than the nonglycosylated [D-Tyr2,Ser4]DDAVP and DDAVP on intraintestinal administration in rat. The improved bioavailability resulted from an increased absorption from the small intestine and most likely from an increased stability toward enzymatic degradation, whereas plasma clearance was either unaffected or slightly increased by the glycosylation. The glycosylated analogues displayed only very low agonistic and antagonistic activities at the vasopressin V2-receptor. Conformational studies performed by 1H NMR spectroscopy did not reveal any major influence from glycosylation on the conformation of the peptide backbone. The lack of receptor binding displayed by the analogues is therefore most likely explained by steric repulsion between the carbohydrate moiety and the vasopressin receptor which prevents receptor binding.
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PMID:Glycosylated peptide hormones: pharmacological properties and conformational studies of analogues of [1-desamino,8-D-arginine]vasopressin. 783 27

Desmopressin is a synthetic analog of the peptide hormone vasopressin in which the N-terminal alpha-amino group has been removed and L-arginine in position 8 has been replaced by D-arginine. Using 1H-NMR spectroscopy, we show that desmopressin binds to neurophysin-II, whereas deamino-vasopressin does not bind. Thus, the change in configuration at Arg8 causes a significant difference in the binding of these hormones to neurophysin-II. We have determined the structure of desmopressin bound to neurophysin-II using two-dimensional 1H nuclear magnetic resonance-transferred nuclear Overhauser effect techniques. A common binding motif for vasopressin and desmopressin is proposed that includes a positive charge group along with the hydrophobic surface formed by the side chains of Tyr2 and a beta-methylene provided by Phe-3. In vasopressin, the positive charge is provided by the N-terminal NH3+, whereas in desmopressin, the side chain of Arg-8 contributes the positive charge. The type II beta-turn found in residues Cys6-Pro7-D-Arg8-Gly9 of the bound structure of desmopressin folds the Arg8 side chain back toward the disulfide-bond loop, which allows the positive charged side chain of Arg8 to participate in binding. Such a type II beta-turn is not found in deamino-vasopressin in the presence of neurophysin-II.
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PMID:Differential binding of desmopressin and vasopressin to neurophysin-II. 894 Jan 42

Via the refinement process of the monomer form of an arginine-vasopressin-like insect factor, the paper analyses the most relevant NMR information to define the solution structure of a flexible peptide. The relative importance of the different NOE constraints is discussed.
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PMID:Constrained refinement based on NOE and chemical shift information: the monomer form of arginine-vasopressin-like insect factor. 923 Apr 78

We have synthesized and fully characterized by fast-atom-bombardment-mass, NMR and ultraviolet spectroscopies the vasopressin antagonist 3-azidophenylpropionyl-D-Tyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-Tyr(3I )-NH2. Easily radioiodinatable just before use, it has a high affinity for the natural rat liver V1a receptor [dissociation constant (Kd) = 54 +/- 20 pM; Carnazzi, E., Aumelas, A., Barberis, C., Guillon, G. & Seyer, R. (1994) J. Med. Chem. 37, 1841-1849] and for both the rat vasopressin V1a receptor expressed in Spodoptera frugiperda 9 cells (Sf9 cells, Kd = 688 +/- 35 pM) and in COS-7 cells (Kd = 320 +/- 20 pM). This probe labels specifically the V1a receptors in an ultraviolet-dependent manner, and binds covalently to about 12% of the receptors with high stability over several days, even in dissociation or solubilization conditions. SDS/PAGE studies and autoradiographic analyses of the photolabeled receptors reveal a single band (49.5 kDa) and two bands (63 kDa and 93.6 kDa) for receptor-probe associations obtained in Sf9 and COS-7 cells respectively. These molecular masses are consistent with non-glycosylated and highly glycosylated forms of the receptor, according to each expression system. In rat liver membranes, we have identified apparent molecular masses of about 32, 45 and more than 67 kDa. We finally demonstrated a proteolysis of the receptor that appeared to be Zn2+ and leupeptin sensitive. The high potency of this ligand is promising for the monitoring of the purification of the V1a receptor and for mapping its antagonist-binding site.
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PMID:Efficient photoaffinity labeling of the rat V1a vasopressin receptor using a linear azidopeptidic antagonist. 928 14

Desmopressin (1-desamino-[DArg8]vasopressin, is a synthetic analogue of the neurohypophyseal peptide hormone vasopressin which has high antidiuretic and antibleeding potency. The structure of desmopressin has been determined in aqueous solution by two-dimensional NMR techniques and molecular dynamics simulations. Both standard and time-averaged distance restraints were used in structure calculations because of the inherent flexibility in small peptides. 21 models calculated with standard restraints were compared with structures refined with time-averaged distance restraints and were found to be good representatives of the conformational ensemble of desmopressin. The macrocyclic ring forms an inverse gamma-turn centered around Gln4. Residues 1 and 2, the disulphide bridge and the three-residue acyclic tail were found to be flexible in solution. Residues 4-6 in the ensemble of calculated structures contain essentially the same backbone conformation as in the crystal structure of pressinoic acid, the cyclic moiety of vasopressin, whereas residues 2-6 superimpose on the NMR-derived conformation of oxytocin bound to neurophysin. The results presented in this work suggest that, in addition to the differences in sequence between desmopressin and vasopressin, differences in conformational and dynamic properties between the two compounds explain their pharmacological differences.
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PMID:Conformation of desmopressin, an analogue of the peptide hormone vasopressin, in aqueous solution as determined by NMR spectroscopy. 954 58

Solution structures of two analogues of vasopressin with an amino acid sequence of c[Mpa1-Tyr2-Phe3-Gln4-Asn5-Cys6]-Xaa7-Arg8-Gly9-NH2 (Xaa = Sar [I] or MeAla [II]) were established using ROE and the 3J(HNH alpha) couplings. Each of the peptides was found to exist in two stable isomers, pertaining to the cis or trans status of the Cys6-Xaa7 peptide bond, thus giving rise to four study objects. Two methods for studies of the conformational properties of the structures were compared. In the first, the algorithm consisted of three steps: (i) An Electrostatically Driven Monte-Carlo (EDMC) search for low-energy conformations. (ii) Simulations of the NOESY spectra and the vicinal couplings for these conformations. (iii) Determination of the statistical weights of the conformations with the ANALYZE package, so as to meet the best fit of the averaged NOE intensities and couplings to the experimental data. In the second method, the distance constraints and the torsion angles were used as the usual constraints in the Distance Geometry and Simulated Annealing algorithms. The flexibility of the pressin ring and the C-terminus was characterized by a large number of families of conformations. The presence of the beta-turn at position 4,5 was confirmed for all low energy structures found. The use of the EDMC method for the elaboration of the NMR data for small flexible peptides yielded an adequate description of their conformational diversity and is the method of choice for the analysis of their solution structures.
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PMID:Conformational solution studies of (Sar7)desamino- and (MeAla7)desamino-vasopressin analogues using NMR spectroscopy. 1214 84

In order to produce large amounts of human vasopressin and oxytocin receptors compatible with direct structural biology approaches such as X-ray crystallography, NMR or mass spectrometry, we have expressed these neurohypophysial hormone receptors in Escherichia coli. To facilitate the level of expression, the coding sequence for the V1a vasopressin receptor and the oxytocin receptor were first optimized for bacterial expression. The resulting 'bacterial receptor cDNAs' were then subcloned into pET/T7-driven prokaryotic expression vectors. Different constructs have been prepared: each cDNA was incorporated alone or in fusion with a T7 tag sequence or a glutathione-S-transferase tag sequence at the N-terminus end. Moreover, a 6 x His tag sequence has been added at the C-terminus end for one-step purification of the receptors. Screening of BL21(DE3) and BL21(DE3)pLysS bacterial strains transformed with the different constructions was achieved by Coomassie blue-stained SDS-polyacrylamide gels and by 6 x His antibody Western blotting. Several clones were selected for purification of the receptors. Expression levels of the receptors are now encouraging and will be optimized for further structural and functional studies. Moreover, at the same time, the construction of the bacterial-optimized sequence of the V2 vasopressin receptor and its expression will be performed.
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PMID:Expression of human vasopressin and oxytocin receptors in Escherichia coli. 1243 34

Vasopressin (VP) receptors belong to the widespread G protein-coupled receptor family. The crucial role of VP receptor intracellular loops in the coupling with the heterotrimeric G proteins was previously demonstrated by construction of a vasopressin receptor chimera. Yet, no fine structural data are available concerning the receptor molecular determinants involved in their interactions with G proteins. In this study, we synthesized both a linear and a cyclic form of the second intracellular loop (i2) of the human V(1a) vasopressin receptor isoform that is important for the interaction between the alphaq/alpha11 G protein and the receptor. These two peptides are biologically active. They specifically inhibit vasopressin binding to the V(1a) receptor, suggesting that the corresponding endogenous peptides contribute to the structure of the vasopressin binding site via intra- or intermolecular interactions with the core of the V(1a) receptor. The i2 peptide structures were determined by (1)H NMR. Both exhibit a helix and helical elements in their N- and C-terminal parts, respectively, separated by a turn imposed by a proline residue. More interestingly, the central Pro-Leu motif conserved in many GPCRs and thought to be important for coupling to G proteins can adopt different conformations. The "U" shape structure of the i2 loop is compatible with its anchoring to transmembrane domains III and IV and is very similar to the shape of bovine rhodopsin i2. Altogether, these data contribute to a better understanding of the structure of a not yet crystallized GPCR using the mimetic peptide approach.
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PMID:Active peptidic mimics of the second intracellular loop of the V(1A) vasopressin receptor are structurally related to the second intracellular rhodopsin loop: a combined 1H NMR and biochemical study. 1284 69


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