[1-β-Mercaptopropionic acid, 8-α-amino-β-guanidinopropionic acid]vasopressin and [1-β-mercaptopropionic acid, 8-D-α-amino-β-guanidinopropionic acid]vasopressin; Analogs showing a high and specific antidiuretic effect

1979 ◽  
Vol 44 (8) ◽  
pp. 2447-2450 ◽  
Author(s):  
Milan Zaoral ◽  
Viktor Krchňák ◽  
František Brtník ◽  
Alena Machová ◽  
Jana Škopková
Keyword(s):  
Hydrogen Fluoride ◽  
Arginine Vasopressin ◽  
Liquid Hydrogen ◽  
Protecting Groups ◽  
Pressor Effect ◽  
Mercaptopropionic Acid ◽  
Antidiuretic Effect

β-Benzylthiopropionyl-tyrosyl-phenylalanyl-glutaminyl-asparaginyl-S-benzylcysteine azide was condensed with prolyl-α-amino-nitroguanidinopropionyl-glycine amides (L2; D2) to β-benzylthiopropionyl-tyrosyl-phenylalanyl-glutaminyl-asparaginyl-S-benzylcysteinyl-prolyl-α-amino-β-nitroguanidinopropionyl-glycine amides (L8; D8) which after removal of the protecting groups in liquid hydrogen fluoride, closure of the disulfide ring, desalting, and electrophoretic purification afforded [1-β-mercaptopropionic acid, 8-α-amino-β-guanidinopropionic acid]vasopressin (I) and [1-β-mercaptopropionic acid, 8-D-α-amino-β-guanidinopropionic acid]vasopressin (II). The antidiuretic effect of I (II) is about 10% of the effect of [1-β-mercaptopropionic acid, 8-D-arginine]vasopressin (DDAVP) (87 ± 8% DDAVP), the pressor effect is 49.5 I.U./mg (2.7 I.U./mg).

[1-β-Mercaptopropionic acid, 8-norarginine]vasopressin and [1-β-mercaptopropionic acid, 8-D-norarginine]vasopressin. Two analogs with strong biological effects

1979 ◽  
Vol 44 (4) ◽  
pp. 1179-1186 ◽  
Author(s):  
Milan Zaoral ◽  
František Brtník ◽  
Martin Flegel ◽  
Tomislav Barth ◽  
Alena Machová
Keyword(s):  
Biological Effects ◽  
Disulfide Bridge ◽  
Protecting Groups ◽  
Pressor Effect ◽  
Amino Groups ◽  
Mercaptopropionic Acid ◽  
Antidiuretic Effect ◽  
Carbodiimide Method

[1-β-Mercaptopropionic acid, 8-norarginine]vasopressin (L8, D8; I, II) was prepared by condensation of β-benzylthiopropionyl-tyrosyl-phenylalanyl-glutaminyl-asparaginyl-S-benzylcysteine with Nγ-benzyloxycarbonyl-α,γ-diaminobutyryl-glycine amide (L2, D2) by the azide or carbodiimide method, respectively, removal of the benzyloxycarbonyl residue, guanidination of γ-amino groups, removal of protecting groups, closing of the disulfide bridge, and electrophoretic purification. I has an almost 2 times higher antidiuretic effect than DDAVP and a 3 times higher pressor effect than AVP. II has 20-25% of the antidiuretic effect of DDAVP and 16 IU/mg of the pressor effect.

Synthesis of oxytocin, arginine-vasopressin and its deamino-analogue using 2,4,6-trimethylbenzyl group for protection of the cysteine sulfur

1981 ◽  
Vol 46 (1) ◽  
pp. 286-299 ◽  
Author(s):  
František Brtník ◽  
Milan Krojidlo ◽  
Tomislav Barth ◽  
Karel Jošt
Keyword(s):  
Peptide Synthesis ◽  
Hydrogen Fluoride ◽  
Sulfur Atom ◽  
Arginine Vasopressin ◽  
Liquid Hydrogen ◽  
Trifluoromethanesulfonic Acid ◽  
Protecting Groups ◽  
Mild Conditions

Preparation of oxytocin, arginine-vasopressin and its deamino-analogue serves as an example of use of 2,4,6-trimethylbenzyl group for protection of the cysteine sulfur atom in the peptide synthesis. This modified benzyl group is sufficiently stable under conditions of solvolytic removal of common amino-protecting groups and it can be cleaved off under mild conditions with liquid hydrogen fluoride or trifluoromethanesulfonic acid.

Vasopressin and oxytocin analogs with interchanged sequence of amino acids in positions 7 and 8. synthesis and biological effects

1981 ◽  
Vol 46 (9) ◽  
pp. 2136-2139 ◽  
Author(s):  
Ivo Bláha ◽  
Viktor Krchňák ◽  
Milan Zaoral
Keyword(s):  
Amino Acids ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Biological Effects ◽  
Free Flow ◽  
Protecting Groups ◽  
Pressor Effect ◽  
Phase Synthesis ◽  
Antidiuretic Effect

p-Toluenesulfonyl-S-benzylcysteinyl-tyrosyl-phenylalanyl-glutaminyl-asparaginyl-S-benzylcysteinyl-NG-p-toluenesulfanylarginyl-prolyl-glycineamide (I) and S-benzylcysteinyl-tyrosyl-isoleucyl-glutaminyl-asparaginyl-S-benzylcysteinyl-leucyl-prolyl-glycine amide (III) were prepared by solid phase synthesis. After removal of the protecting groups, closure of the disulfide ring, and purification by continuous free-flow electrophoresis [arginine7, proline8]vasopressin (II) and [leucine7, proline8]oxytocin (IV) were obtained. The antidiuretic effect of II is markedly higher than its pressor effect; IV possesses c. 6% of the uterotonic and c. 10% of the galactogogous effect of oxytocin.

[1-β-Mercaptopropionic acid, 8-α,β-diaminopropionic acid]vasopressin and [1-β-mercaptopropionic acid, 8-D-α,β-diaminopropionic acid]vasopressin. Two lysine-vasopressin analogs with considerable antidiuretic effect

1979 ◽  
Vol 44 (7) ◽  
pp. 2161-2164 ◽  
Author(s):  
Viktor Krchňák ◽  
Milan Zaoral ◽  
Alena Machová
Keyword(s):  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Pressor Effect ◽  
Phase Synthesis ◽  
Mercaptopropionic Acid ◽  
Antidiuretic Effect ◽  
Lysine Vasopressin ◽  
Diaminopropionic Acid

Two lysine-vasopressin analogs, [1-β-mercaptopropionic acid, 8-α,β-diaminopropionic acid]vasopressin (IVa) and [1-β-mercaptopropionic acid, 8-D-α,β-diaminopropionic acid]vasopressin (IVb) were prepared by solid phase synthesis. IVa and IVb show a considerable antidiuretic effect (1 079 and 1 000 I.U./mg, resp.) and a low pressor effect (14.0 and 22.8 I.U./mg, resp.). The uterotonic effect of IVa is 0.9 I.U./mg and of IVb 1.72 I.U./mg.

Effect of methylation of the hydroxyl group of tyrosine in [1-β-mercaptopropionic acid, 8-D-arginine]vasopressin on its biological effects

1979 ◽  
Vol 44 (5) ◽  
pp. 1642-1644 ◽  
Author(s):  
Viktor Krchňák ◽  
Milan Zaoral
Keyword(s):  
Arginine Vasopressin ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Biological Effects ◽  
Hydroxyl Group ◽  
Rat Uterus ◽  
Phase Synthesis ◽  
Mercaptopropionic Acid ◽  
Antidiuretic Effect

Using the method of solid-phase synthesis, S-benzyl-β-mercaptopropionyl-O-methyltyrosyl-phenylalanyl-glutaminyl-asparaginyl-S-benzylcysteinyl-prolyl-NG-p-toluenesulfonyl-D-arginyl-glycine amide (I) was prepared which after removal of the protecting groups, oxidation, and purification afforded [1-β-mercaptopropionic acid, 2-O-methyltyrosine, 8-D-arginine]vasopressin (II). II shows a low antidiuretic effect, c. 10 I.U./mg. It is without effect on rat uterus in vitro and on the blood pressure of rat in vitro.

ELIMINATION OF INFUSED ARGININE-VASOPRESSIN AND ITS LONG-ACTING DEAMINATED ANALOGUE IN RATS

1978 ◽  
Vol 78 (2) ◽  
pp. 179-186 ◽  
Author(s):  
DIANA GAZIS ◽  
W. H. SAWYER
Keyword(s):  
Arginine Vasopressin ◽  
Plasma Concentrations ◽  
Metabolic Clearance ◽  
Prolonged Infusion ◽  
Exponential Functions ◽  
Antidiuretic Effect ◽  
Long Acting ◽  
Deamino Arginine Vasopressin

SUMMARY Arginine-vasopressin (AVP) and deamino-arginine-vasopressin (dAVP) were infused into rats. When the concentrations of the two peptides were steady, the rate of clearance of AVP from the plasma was six times the rate of clearance of dAVP. Only 6% of the infused AVP was excreted unchanged in the urine, whereas approximately 100% of the dAVP was excreted. When the infusions were stopped, AVP disappeared from the plasma much more rapidly than dAVP. The plasma concentrations of the two peptides did not decay as simple exponential functions, suggesting that both AVP and dAVP entered a slowly exchanging compartment or compartments during prolonged infusion. These differences in the metabolic clearance of AVP and dAVP may well explain the prolonged antidiuretic effect of dAVP in rats.

Synthesis of [1-β-mercaptopropionic acid, 8-D-arginine]vasopressin (DDAVP) in solid phase. Simple optimalization

1979 ◽  
Vol 44 (4) ◽  
pp. 1173-1178 ◽  
Author(s):  
Viktor Krchňák ◽  
Milan Zaoral
Keyword(s):  
Arginine Vasopressin ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Experimental Conditions ◽  
Phase Synthesis ◽  
Mercaptopropionic Acid ◽  
Better Than

A series of solid-phase syntheses of the protected precursor II of DDAVP was carried out. Experimental conditions were developed under which practically pure II can reproducibly be obtained in yields better than 60%. The protected precursors of DDAVP obtained by liquid- and solid-phase synthesis and DDAVP samples obtained from these precursors were undistinguishable by conventional analytical or pharmacological assays.

Acute Effect of Parathyroid Hormone on Urine Concentration in the Rat

1995 ◽  
Vol 88 (2) ◽  
pp. 197-201 ◽  
Author(s):  
S. L. Carney ◽  
A. H. B. Gillies
Keyword(s):  
Parathyroid Hormone ◽  
Arginine Vasopressin ◽  
Partial Agonist ◽  
Acute Effect ◽  
Inhibitory Effect ◽  
Urine Concentration ◽  
Antidiuretic Effect ◽  
Plasma Calcium Concentration ◽  
Subsequent Effect

1. It has been demonstrated that parathyroid hormone can increase adenylate cyclase activity in the rat papilla, produce a small antidiuretic effect and in vitro can interfere with the action of arginine vasopressin on water transport. Clearance studies were performed in the anaesthetized water diuretic thyroparathyroidectomized rat to evaluate further the effect of parathyroid hormone on urine concentration in the presence and absence of arginine vasopressin. 2. A maximal phosphaturic concentration of rat parathyroid hormone (2 μg/kg) reduced urine flow from 125 ± 7 to 81 ± 9 μl/min within 10 min (P < 0.01). Addition of a maximal antidiuretic concentration of arginine vasopressin (100 ng/kg) produced a delayed and diminished antidiuretic response when compared with a group of rats not pretreated with parathyroid hormone (47 ± 5 compared with 27 ± 5 μl/min; P < 0.01). However, a supramaximal arginine vasopressin concentration (1000 ng/kg) produced a maximal antidiuretic effect in the presence of parathyroid hormone. 3. To evaluate further the inhibitory effect of parathyroid hormone on arginine vasopressin-induced anti-diuresis, parathyroid hormone (2 μg/kg) was administered to one group of rats and a minimally effective arginine vasopressin concentration (7.5 ng/kg) to another group, which produced a similar antidiuretic effect. However, the subsequent effect of a maximal antidiuretic arginine vasopressin concentration (100 ng/kg) was again significantly blunted in the group pretreated with parathyroid hormone. 4. Parathyroid hormone produced only a small increase in mean plasma calcium concentration, and glomerular filtration rate was not altered by either hormone. 5. These results demonstrate that high physiological concentrations of parathyroid hormone do have a significant antidiuretic effect and can interfere with the action of arginine vasopressin. This suggests that parathyroid hormone may act as a partial agonist to arginine vasopressin in the collecting system.

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