[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.

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-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-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.

Vasopressin analogs modified in position 3. Influence of changes of configuration

1979 ◽  
Vol 44 (10) ◽  
pp. 3128-3132 ◽  
Author(s):  
Milan Zaoral ◽  
Danuta Konopinska ◽  
Ivan Bláha ◽  
Viktor Krchňák ◽  
Jana Škopková ◽  
...  
Keyword(s):  
Methyl Ester ◽  
Disulfide Bridge ◽  
Protecting Groups ◽  
Diaminobutyric Acid ◽  
Antidiuretic Effect ◽  
Phenylalanine Methyl Ester

The condensation of p-toluenesulfonyl-S-benzylcysteinyl-tyrosine azide with D-phenylalanine methyl ester afforded p-toluenesulfonyl-S-benzylcysteinyl-tyrosyl-D-phenylalanine methyl ester which was subsequently converted into the hydrazide and azide and coupled with glutaminyl-asparaginyl-S-benzylcysteine methyl ester. p-Toluenesulfonyl-S-benzylcysteinyl-tyrosyl-D-phenylalanyl-glutaminyl-asparaginyl-S-benzylcysteine methyl ester was condensed via the hydrazide and azide with prolyl-Nγ-p-toluenesulfonyl-αγ-diaminobutyryl-glycine amide. After removal of the protecting groups, closure of the disulfide bridge and purification, [3-D-phenylalanine, 8-α,γ-diaminobutyric acid]vasopressin was obtained which shows an appreciable antidiuretic effect of distinct specifity.

Coupling of Steroid O-(Carboxymethyl)oxime Derivatives with Single-Protected α,ω-Diaminoalkanes

1999 ◽  
Vol 64 (12) ◽  
pp. 2035-2043 ◽  
Author(s):  
Vladimír Pouzar ◽  
Ivan Černý ◽  
Pavel Drašar
Keyword(s):  
Trifluoroacetic Acid ◽  
Protecting Groups ◽  
Oxime Group ◽  
Amino Groups ◽  
New Approach ◽  
Terminal Amino ◽  
Oxime Derivatives

New approach to the synthesis of steroid oximes bearing O-substituents with terminal amino groups was described. The easily accessible steroid O-(carboxymethyl)oximes were reacted with single-protected Boc-α,ω-diaminoalkanes to give corresponding amide intermediates. From them the Boc protecting groups were cleaved with trifluoroacetic acid to afford the desired steroid derivatives with terminal amino groups. The procedure was succesfully tested on steroids with O-(carboxymethyl)oxime group in positions 7 and 17. The decomposition of target products was observed during deprotection of substituted 19-oximes.

scholarly journals Role of capping in peptide synthesis

2020 ◽  
Vol 11 (4) ◽  
pp. 5225-5228
Author(s):  
Deepshikha Verma ◽  
Pillai V N R ◽  
Giriraj Tailor
Keyword(s):  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Protecting Groups ◽  
Amino Groups ◽  
Peptide Chemistry ◽  
Fmoc Spps ◽  
Reliable Methods ◽  
Important Test

Protecting groups like Fmoc and coupling both steps are essential to monitoring the Fmoc SPPS (Solid Phase Peptide Synthesis) reaction completion. Reliable methods are used to detect the unreacted number of amino groups for monitoring these two essential reaction steps of coupling and cleavage. The ability to detect the complete coupling, incomplete coupling or failure of coupling we use many colour tests in the laboratory and based on this the Fmoc peptide chemistry allows the control of the completion of the Fmoc cleavage. The most important test used is the Kaiser test and highly recommended to monitor the coupling and cleavage steps. If the result of colour tests is positive after coupling, then the second coupling should be performed. Then again use the colour test to detect the level of coupling. If the result is still slightly positive, repeat coupling with the smaller modification of reagents such as used PyBOP instead of HOBT AND HOAT. These colour tests help in revealing the presence of unreacted amino-functional groups. Thus, we need to block these free N-terminal of amino- acids which help in avoiding the making of deletion of sequence.

Condensation de la poly-L-lysine et de la poly- L-ornithine avec des dérivés de bases puriques et de sulfamides

1969 ◽  
Vol 47 (19) ◽  
pp. 3641-3646 ◽  
Author(s):  
Louis Berlinguet ◽  
Jacky Gautier
Keyword(s):  
Aqueous Solution ◽  
Amino Acids ◽  
Free Amino ◽  
Sulfonyl Chloride ◽  
Amino Groups ◽  
Carbodiimide Method

Free ε-amino groups of poly-L-lysine and poly-L-ornithine were alkylated in aqueous solution with 6-chloropurine and 6-chloropurine-riboside, were acylated with 4-acetylamino benzene sulfonyl chloride, and were condensed with N-(4-acetylamino benzene sulfonyl)-glycine using carbodiimide method. Approximately 50% of the free amino groups of the basic polypetides were substituted. The same method was used to prepare poly-α-amino acids bearing radioactive substituants.

Synthesis and Biological Effects of Acyclic Analogs of Deazapurine Nucleosides

1993 ◽  
Vol 58 (3) ◽  
pp. 629-648 ◽  
Author(s):  
Hana Dvořáková ◽  
Antonín Holý ◽  
Ivan Votruba ◽  
Milena Masojídková
Keyword(s):  
Biological Activity ◽  
Acid Hydrolysis ◽  
Acid Medium ◽  
Biological Effects ◽  
Protecting Groups ◽  
Diethyl Acetal ◽  
Subsequent Removal ◽  
Antiviral Activities ◽  
Cesium Salts

Deaza analogs of three basic types of S-adenosyl-L-homocysteine hydrolase (SAHase) inhibitors, (S)-DHPA (I), eritadenine (II) and AHPA (III), were prepared. Alkylation of 3-deazaadenine (V), 3-deazapurine (VI), 1-deazaadenine (VII) and 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidine (XXII) with (R)-2,2-dimethyl-4-tosyloxymethyl-1,3-dioxolane (XIIIb), followed by acid hydrolysis, afforded the corresponding (S)-2,3-dihydroxypropyl derivatives XVIIa -XIXa and XXV. Reaction of V and VII with 2,3-O-cyclohexylidene-D-erythrono lactone (XXIX) and subsequent removal of the protecting groups in an acid medium gave eritadenine analogs XXVII and XXVIII. Compounds V and VII were alkylated with bromoacetaldehyde diethyl acetal to give N-(2,2-diethoxyethyl) derivatives XXXII and XXXIII from which the substituted acetaldehyde derivatives were liberated in situ and converted into compounds XXX and XXXI by cyanohydrine reaction followed by acid hydrolysis. The alkylations were performed in dimethylformamide with sodium or cesium salts of the bases. Biological activity was observed only with 3-deazaadenine derivatives XVIIa, XXVII and XXX, which exhibit both enzyme-inhibitory and antiviral activities.

EFFECTS OF 8-LYSINE-VASOPRESSIN AND SYNTHETIC ANALOGUES ON RELEASE OF ACTH

1972 ◽  
Vol 69 (4) ◽  
pp. 640-648 ◽  
Author(s):  
K.-E. Andersson ◽  
B. Arner ◽  
P. Hedner ◽  
J. L. Mulder
Keyword(s):  
Cortisol Level ◽  
Plasma Cortisol ◽  
Normal Subjects ◽  
Plasma Cortisol Level ◽  
Pressor Effect ◽  
Synthetic Analogues ◽  
Antidiuretic Effect ◽  
Lysine Vasopressin ◽  
Cortisol Increase ◽  
Antidiuretic Action

ABSTRACT Two synthetic analogues of vasopressin, [N-α-triglycyl-8-lysine]-vasopressin (GVP) and [1-deamino-8-D-arginine]-vasopressin (DDAVP), with a pronounced and long-lasting pressor and antidiuretic action respectively, were given to healthy volunteers in order to investigate whether the ACTH-releasing ability of vasopressin, reflected by plasma cortisol increase, is related to its pressor or to its antidiuretic effect. The effecti'veness of 3 different intravenous doses of [8-lysine]-vasopressin (LVP) in causing release of ACTH was also studied, and the responses compared with that caused by LVP given intramuscularly, the usually recommended route of administration. The lowest dose of LVP used in this study, 1 μg (0.25 IU) intravenously, caused a significant change of plasma cortisol. Doses of GVP with a pressor effect comparable to that of 8 μg of LVP did not affect the plasma cortisol level significantly in spite of obvious pressor effects. Nor did DDAVP in doses which should exert a maximal antidiuretic effect (4 and 16 μg) increase the plasma cortisol level. In 2 out of 10 subjects, 40 μg of LVP (10 IU) given intramuscularly failed to give a rise in plasma cortisol exceeding 5μg/100 ml, which is generally required for regarding the response as normal, and also 16 μg (4 IU) of LVP intravenously failed to produce a response reaching this level in 1 out of 12 subjects. It is concluded that the ACTH-releasing ability of vasopressin is neither associated with its pressor nor with its antidiuretic action. The finding that normal subjects can have a low response to vasopressin reduces its value for testing the function of the hypothalamic-pituitary – adrenocortical system.

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