Vasopressin analogues modified in positions 2, 3 and 8. Synthesis and biological effects

1983 ◽  
Vol 48 (5) ◽  
pp. 1341-1351 ◽  
Author(s):  
Ivo Bláha ◽  
Danuta Konopinska ◽  
Milan Zaoral
Keyword(s):  
Amino Acid ◽  
Solid Phase ◽  
Biological Effects ◽  
Solution Synthesis ◽  
Antidiuretic Activity ◽  
Pressor Activity ◽  
Vasopressin Analogues

Four vasopressin analogues, modified in positions 2, 3 and 8 were prepared by solid phase as well as solution synthesis. Analogues, containing a D-amino acid in position 3, exhibit a low but markedly specific antidiuretic activity. Analogues with a D-substituent in position 2 show a more specific pressor activity.

Basic principles

1999 ◽  
Author(s):  
Peter D. White ◽  
Weng C. Chan
Keyword(s):  
Amino Acid ◽  
Amino Acid Residue ◽  
Solid Phase ◽  
Analytical Techniques ◽  
Amide Bond ◽  
Peptide Chain ◽  
Side Reactions ◽  
Protecting Group ◽  
Solution Synthesis ◽  
Resin Loading

Construction of a peptide chain on an insoluble solid support has obvious benefits: separation of the intermediate peptides from soluble reagents and solvents can be effected simply by filtration and washing with consequent savings in time and labour over the corresponding operations in solution synthesis; many of the operations are amenable to automation; excess reagents can be employed to help to drive reactions to completion; and physical losses can be minimized as the peptide remains attached to the support throughout the synthesis. This approach does, however, have its attendant limitations. By-products arising from either incomplete reactions, side reactions, or impure reagents will accumulate on the resin during chain assembly and contaminate the final product. The effects on product purity of achieving less than 100% chemical efficiency in every step are illustrated dramatically in Table 1. This has serious implications with regard to product purification as the impurities generated will, by their nature, be very similar to the desired peptide and therefore extremely difficult to remove. Furthermore, the analytical techniques employed for following the progress of reactions in solution are generally not applicable, and recourse must generally be made to simple qualitative colour tests to detect the presence of residual amines on the solid phase. The principles of solid phase synthesis are illustrated in Figure 1. The C-terminal amino acid residue of the target peptide is attached to an insoluble support via its carboxyl group. Any functional groups in amino acid side chains must be masked with permanent protecting groups that are not affected by the reactions conditions employed during peptide chain assembly. The temporary protecting group masking the α-amino group during the initial resin loading is removed. An excess of the second amino acid is introduced, with the carboxy group of this amino acid being activated for amide bond formation through generation of an activated ester or by reaction with a coupling reagent. After coupling, excess reagents are removed by washing and the protecting group removed from the N-terminus of the dipeptide, prior to addition of the third amino acid residue.

Synthesis and biological properties of vasopressin analogues containing 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

1990 ◽  
Vol 55 (4) ◽  
pp. 1099-1105 ◽  
Author(s):  
Zdenko Procházka ◽  
Juris E. Ancans ◽  
Jiřina Slaninová ◽  
Alena Machová ◽  
Tomislav Barth ◽  
...  
Keyword(s):  
Amino Acid ◽  
Carboxylic Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Biological Activities ◽  
Biological Properties ◽  
Phase Synthesis ◽  
Aromatic Residues ◽  
Synthesis Methodology ◽  
Vasopressin Analogues

Solid phase synthesis methodology on a benzhydrylamine resin was used for the synthesis of three analogues of vasopressin with the non-coded amino acid, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), in the position 2 ([Tic2, Lys8]VP (I)) and in the position 3 ([Tic3, Lys8]VP (II)). The analogue containing only one Tic in place of both aromatic residues was also isolated (des-Tyr2-[Tic3, Lys8]VP (III)). The biological activities of all analogues were negligible.

Amino and Deamino Analogs of 8-D-Homoarginin-vasopressin with Modified Tyrosine in Position 2: Synthesis and Some Biological Properties

1992 ◽  
Vol 57 (3) ◽  
pp. 604-613 ◽  
Author(s):  
Miroslava Žertová ◽  
Zdenko Procházka ◽  
Jiřina Slaninová ◽  
Jana Škopková ◽  
Tomislav Barth ◽  
...  
Keyword(s):  
Amino Acid ◽  
Solid Phase ◽  
Biological Properties ◽  
Antidiuretic Activity

Solid phase methodology on benzhydrylamine or p-methylbenzhydrylamine resin was used for the synthesis of seven analogs of amino or deamino vasopressin with non-coded amino acid, D-homoarginine, in position 8 and D- or L- O-methyl or O-ethyl tyrosine in position 2. [L-Tyr-(Me)2, D-Har8]vasopressin (I), [D-Tyr(Me)2, D-Har8]vasopressin (II), [L-Tyr(Et)2, D-Har8]vasopressin (III), [D-Tyr(Et)2, D-Har8]vasopressin (IV), [Mpr1, L-Tyr(Me)2, D-Har8]vasopressin (V), [Mpr1, D-Tyr(Me)2, D-Har8]vasopressin (VI) and [Mpr1, D-Tyr(Et)2, D-Har8]vasopressin (VII) were synthesized. All analogs have very low antidiuretic activity. Analogs containing O-methyltyrosine of D-configuration or O-ethyltyrosine of both D- and L-configuration are low pressor inhibitors. All analogs were found to be uterotonic inhibitors, the most potent one in vitro being [Mpr1, D-Tyr(Me)2, D-Har8]vasopressin (VI) with pA2 = 9.0 and [Mpr1, D-Tyr(Et)2, D-Har8]vasopressin (VII) with pA2 = 8.8.

Mimicking bioactive peptides. [8-Nβ-Guanidoacetyl-α,β-diaminopropionic acid]vasopressin

1989 ◽  
Vol 54 (2) ◽  
pp. 533-535
Author(s):  
Milan Zaoral ◽  
Viktor Krchňák
Keyword(s):  
Title Compound ◽  
Bioactive Peptides ◽  
Solid Phase ◽  
Antidiuretic Activity ◽  
Pressor Activity ◽  
Diaminopropionic Acid

The title compound was prepared by solid phase methodology. It has 34.2 I.U./mg of pressor activity, 5.8 I.U./mg of uterotonic activity and by 3-4 orders of magnitude lower antidiuretic activity than DDAVP.

A Strategy for Thioamide Incorporation During Fmoc Solid-Phase Peptide Synthesis with Robust Stereochemical Integrity

2019 ◽  
Author(s):  
luis camacho III ◽  
Bryan J. Lampkin ◽  
Brett VanVeller
Keyword(s):  
Amino Acid ◽  
Functional Groups ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Side Chains ◽  
Amino Acid Side Chains ◽  
Peptide Elongation

We describe a method to protect the sensitive stereochemistry of the thioamide—in analogy to the protection of the functional groups of amino acid side chains—in order to preserve the thioamide moiety during peptide elongation.<br>

Oxytocin analogues with non-coded amino acid residues in position 8: [8-Neopentylglycine]oxytocin and [8-cycloleucine]oxytocin

1987 ◽  
Vol 52 (9) ◽  
pp. 2317-2325 ◽  
Author(s):  
Jan Hlaváček ◽  
Jan Pospíšek ◽  
Jiřina Slaninová ◽  
Walter Y. Chan ◽  
Victor J. Hruby
Keyword(s):  
Amino Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
The Other ◽  
Amino Acid Residues ◽  
Phase Synthesis ◽  
Other Hand ◽  
Fragment Condensation

[8-Neopentylglycine]oxytocin (II) and [8-cycloleucine]oxytocin (III) were prepared by a combination of solid-phase synthesis and fragment condensation. Both analogues exhibited decreased uterotonic potency in vitro, each being about 15-30% that of oxytocin. Analogue II also displayed similarly decreased uterotonic potency in vivo and galactogogic potency. On the other hand, analogue III exhibited almost the same potency as oxytocin in the uterotonic assay in vivo and in the galactogogic assay.

Vasopressin analogues with effect on central nervous system: Synthesis and biological properties

1983 ◽  
Vol 48 (10) ◽  
pp. 2862-2873 ◽  
Author(s):  
František Brtník ◽  
Ivan Krejčí ◽  
Běla Kupková ◽  
Pavel Hrbas ◽  
Jana Škopková ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amino Acid ◽  
Passive Avoidance ◽  
Biological Properties ◽  
Passive Avoidance Test ◽  
System Synthesis ◽  
Avoidance Test ◽  
Vasopressin Analogues

Synthesis of four vasopressin analogues which do not contain the glycinamine residue in position 9 and have a basic non-coded amino acid in position 8 is described. All the analogues exhibit very low endocrine activities and are effective in the passive avoidance test.

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.

Comparison of the Potency of 8-L-Arginine, 8-D-Arginine and 8-D-Homoarginine Vasopressin Analogs with Substituted Phenylalanine in Position 2

1994 ◽  
Vol 59 (6) ◽  
pp. 1439-1450 ◽  
Author(s):  
Miroslava Žertová ◽  
Jiřina Slaninová ◽  
Zdenko Procházka
Keyword(s):  
Amino Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Basic Amino Acid ◽  
The Other ◽  
Side Chain ◽  
Inhibitory Potency ◽  
Phase Synthesis ◽  
Other Hand ◽  
Order Of Magnitude

An analysis of the uterotonic potencies of all analogs having substituted L- or D-tyrosine or -phenylalanine in position 2 and L-arginine, D-arginine or D-homoarginine in position 8 was made. The series of analogs already published was completed by the solid phase synthesis of ten new analogs having L- or D-Phe, L- or D-Phe(2-Et), L- or D-Phe(2,4,6-triMe) or D-Tyr(Me) in position 2 and either L- or D-arginine in position 8. All newly synthesized analogs were found to be uterotonic inhibitors. Deamination increases both the agonistic and antagonistic potency. In the case of phenylalanine analogs the change of configuration from L to D in position 2 enhances the uterotonic inhibition for more than 1 order of magnitude. The L to D change in position 8 enhances the inhibitory potency negligibly. Prolongation of the side chain of the D-basic amino acid in position 8 seems to decrease slightly the inhibitory potency if there is L-substituted amino acid in position 2. On the other hand there is a tendency to the increase of the inhibitory potency if there is D-substituted amino acid in position 2.

Biological effects of rat iso-atrial natriuretic peptide and brain natriuretic peptide are indistinguishable from each other

1992 ◽  
Vol 70 (11) ◽  
pp. 1525-1528 ◽  
Author(s):  
D. A. Wigle ◽  
B. M. Bennett ◽  
D. B. Jennings ◽  
I. R. Sarda ◽  
T. G. Flynn ◽  
...  
Keyword(s):  
Amino Acid ◽  
Atrial Natriuretic Peptide ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Receptor Binding ◽  
Amino Acid Substitution ◽  
Cyclic Gmp ◽  
Cardiovascular Response ◽  
Biological Effects ◽  
Atrial Natriuretic

Rat brain natriuretic peptide (rBNP) and iso-atrial natriuretic peptide (iso-rANP) were discovered independently by two research laboratories. They are considered to be members of the B-type natriuretic peptides. Except for the Gln/Leu substitution at position 44, the amino acid sequence of iso-rANP is identical with that of the C-terminal 45 amino acids of rat pro-BNP and with the 5-kDa cardiac peptide from rat atria. To determine whether this amino acid substitution can modify the known biological effects of rBNP and iso-rANP, the present investigation examined the cardiovascular and renal responses, vasorelaxant effect, receptor binding characteristics, and cyclic GMP production by the two peptides in relation to that of rat atrial natriuretic peptide (rANP). Results indicate that rBNP and iso-rANP are indistinguishable from each other in terms of these known biological activities of atrial natriuretic peptide. We therefore conclude that rBNP and iso-rANP are identical peptides and that the amino acid substitution at position 44 represents a polymorphic form of the rat B-type natriuretic peptide.Key words: atrial natriuretic peptide, brain natriuretic peptide, cardiovascular response, vasorelaxation, cyclic GMP, receptor binding.

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