The Analogs of [D-Har8]Vasopressin with Di- and Trisubstituted Phenylalanine in Position 2; Synthesis and Some Biological Properties

1993 ◽  
Vol 58 (11) ◽  
pp. 2751-2760 ◽  
Author(s):  
Miroslava Žertová ◽  
Zdenko Procházka ◽  
Jiřina Slaninová ◽  
Tomislav Barth ◽  
Pavel Majer ◽  
...  
Keyword(s):  
Amino Acids ◽  
Solid Phase ◽  
Biological Properties ◽  
Phase Method ◽  
Antidiuretic Activity ◽  
Solid Phase Method

Four analogs of vasopressin with non-coded amino acids D-homoarginine (in position 8) and 2,6-di- or 2,4,6-trisubstituted L- or D-phenylalanine (in position 2) were synthesized using the solid phase method on p-methylbenzhydrylamine resin. All the analogs were found to be uterotonic inhibitors, the most potent one in vitro and in vivo being [D-Phe(2,4,6-triMe)2,D-Har8]vasopressin with pA2 values equal to 8.1 and 7.5, respectively. All of them had negligible antidiuretic activity and were weak pressor inhibitors.

Synthetic antagonists of the myometrial response to vasopressin and oxytocin

1986 ◽  
Vol 111 (1) ◽  
pp. 125-131 ◽  
Author(s):  
P. Melin ◽  
J. Trojnar ◽  
B. Johansson ◽  
H. Vilhardt ◽  
M. Åkerlund
Keyword(s):  
Blood Pressure ◽  
Pregnant Women ◽  
Solid Phase ◽  
Phase Method ◽  
Inhibitory Effects ◽  
Inhibitory Potency ◽  
Low Blood Pressure ◽  
Solid Phase Method

ABSTRACT With the aim of developing inhibitors of vasopressin-and oxytocin-induced uterine activity, 17 analogues of 1-deamino-oxytocin were synthesized by the solid-phase method. Modifications were made at positions 2, O-methyltyrosine (Tyr(OMe)) and O-ethyltyrosine (Tyr(OEt)),d-Tyr,d-Tyr(OEt),d-Trp; 4, Val,Thr and 8, Orn,Cit,Arg,d-Arg. The analogues were tested for antiuterotonic activity in vitro and in vivo in the rat and in vitro on myometrial strips from non-pregnant women and pregnant women at term. Their selectivity was also investigated in blood pressure and antidiuretic bioassays in rats. Results were compared with those from an original antiuterotonic analogue 1-deamino-2-Tyr(OEt)-oxytocin (d(OEt)-oxytocin). In the rat in vitro and in vivo all analogues possessed higher antiuterotonic activity than d(OEt)-oxytocin. The negative logarithm of the molar concentration of the antagonist which reduced the effect of a dose of agonist to that of half the dose (pA2) was between 7·6 and 8·9 for all the new inhibitors compared with 7·2 for d(OEt)-oxytocin. The highest pA2 value was found for 1-deamino-2-Tyr(OMe)-8-Orn-oxytocin (8·9 ± 0·2, s.e.m.) and 1-deamino-2-Tyr(OEt)-4-Thr-8-Orn-oxytocin (8·9 ± 0·6). In myometrium from non-pregnant women the most potent peptide was 1-deamino-2-d-Tyr(OEt)-4-Th r-8-Orn-oxytocin (17·2 ± 2·0 times more potent that d(OEt)-oxytocin). In myometrium from pregnant women the inhibitory effects of the majority of the analogues were less pronounced. In the rat in vivo the most potent analogue 1-deamino-2-d-Trp-4-Val-8-Orn-oxytocin was 19·9 ± 2·5 times more active than d(OEt)-oxytocin. Exchanging l-tyrosine for the d form generally increased inhibitory activity as well as specificity of the analogues. Alkylation of the d-tyrosine residue did not appear to be necessary for inhibition. Substitution with d-tryptophan at position 2 gave analogues with high inhibitory potency in the rat in vitro and in vivo, but which exhibited weak effects in women in vitro. There was no correlation between the inhibitory effects on myometrium from non-pregnant and pregnant women nor between rat and human data. The high antiuterotonic activity of 1-deamino-2-d-Tyr(OEt)-4-Val-8-Orn-oxytocin and 1-deamino-2-d-Tyr(OEt)-4-Thr-8-Orn-oxytocin combined with low blood pressure and antidiuretic effects make these two analogues interesting for clinical studies. J. Endocr. (1986) 111, 125–131

Antagonistic Analogs of Oxytocin with Substituted Phenylalanine or Tyrosine in Position 2

1994 ◽  
Vol 59 (6) ◽  
pp. 1430-1438 ◽  
Author(s):  
Rudolf Ježek ◽  
Miroslava Žertová ◽  
Jiřina Slaninová ◽  
Pavel Majer ◽  
Zdenko Procházka
Keyword(s):  
Amino Acids ◽  
Solid Phase ◽  
Phase Method ◽  
Inhibiting Activity ◽  
Structure Activity ◽  
Low Degree ◽  
Solid Phase Method ◽  
Pressor Activity ◽  
Agonistic Activity

Solid phase method on p-methylbenzhydrylamine resin was used for the synthesis of seven analogs of oxytocin with non-coded amino acids in position 2. [L-Phe(4-Me)2]oxytocin (I), [D-Phe(4-Me)2]oxytocin (II), [L-Phe(2-Me,4-Et)2]oxytocin (III), [D-Phe(2-Me,4-Et)2]oxytocin (IV), [D-Tyr(Me)2]oxytocin (V), [D-Tyr(Et)2]oxytocin (VI) and [L-Tyr(2-Me)2]oxytocin (VII) were synthesized. All analogs with D-stereoisomer of alkyl or alkoxy substituted phenylalanine possess uterus in vitro inhibiting activity. In the case of L-stereoisomers the structure activity relationship is more complicated. As far as the pressor activity is concerned, the analogs have either very low agonistic activity or low degree of antagonism.

Self-assembling RATEA16 peptide nanofiber designed for rapid hemostasis

2020 ◽  
Vol 8 (9) ◽  
pp. 1897-1905 ◽  
Author(s):  
Shuda Wei ◽  
Fangping Chen ◽  
Zhen Geng ◽  
Ruihua Cui ◽  
Yujiao Zhao ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Self Assembly ◽  
Solid Phase ◽  
Phase Method ◽  
Self Assembling ◽  
Solid Phase Method ◽  
Assembly Performance

In this study, we synthesized a novel polypeptide material, RATEA16, by the solid phase method, and investigated the secondary structure, self-assembly performance, gelation ability, biocompatibility and hemostatic efficiency in vitro and in vivo.

Synthesis of peptides by the solid-phase method. V. Substance P and analogs

1980 ◽  
Vol 58 (4) ◽  
pp. 272-280 ◽  
Author(s):  
A. Fournier ◽  
R. Couture ◽  
J. Magnan ◽  
M. Gendreau ◽  
D. Regoli ◽  
...  
Keyword(s):  
Substance P ◽  
Solid Phase ◽  
Gel Filtration ◽  
Paper Electrophoresis ◽  
Exchange Chromatography ◽  
Phase Method ◽  
Elemental Analyses ◽  
Solid Phase Method

We have synthesized a series of 12 analogs of the undecapeptide substance P in order to perform a structure–activity study of this peptide. In the present work, each residue was substituted by L-alanine, and the C-terminal amide was replaced by the free carboxyl in order to pinpoint biologically important side chains and functional groups. The synthesis of the analogs was carried out by the automatic solid-phase method. Couplings were performed by the symmetrical anhydride procedure. After cleavage with liquid HF, the peptides were purified by gel filtration and ion-exchange chromatography. Their purity was assessed by thin-layer chromatography, paper electrophoresis, amino acid and elemental analyses, and high pressure liquid chromatography. They were tested for biological activity in vitro on the ileum of the guinea pig, the mesenteric vein of the rabbit, and the vas deferens of the rat, and in vivo by measuring their effect on the blood pressure of the rat.

The Analogs of 8-D-Homoarginin-vasopressin with O-Substituted Phenylalanine in Position 2: Synthesis and Some Biological Properties

1992 ◽  
Vol 57 (5) ◽  
pp. 1103-1110 ◽  
Author(s):  
Miroslava Žertová ◽  
Zdenko Procházka ◽  
Jiřina Slaninová ◽  
Tomislav Barth ◽  
Pavel Majer ◽  
...  
Keyword(s):  
Amino Acids ◽  
Solid Phase ◽  
Biological Properties ◽  
Antidiuretic Activity

Solid phase methodology on p-methylbenzhydrylamine resin was used for the synthesis of four analogs of vasopressin with the non coded amino acids, D-homoarginine (in position 8) and o-substituted L- or D-phenylalanine (in position 2). [L-Phe(o-Me)2,D-Har8]vasopressin (I), [D-Phe(o-Me)2,D-Har8]vasopressin (II), [L-Phe(o-Et)2,D-Har8]vasopressin (III) and [D-Phe(o-Et)2,D-Har8]vasopressin (IV) were synthesized. All analogs had very low antidiuretic activity. Analogs I and IV were low pressor inhibitors. All analogs were found to be the uterotonic inhibitors, the most potent on in vitro being [D-Phe(o-Et)2,D-Har8]vasopressin with a pA2 = 8.4.

Synthesis and biological activity of new metallocenic angiotensin II analogs

1988 ◽  
Vol 53 (11) ◽  
pp. 2914-2919 ◽  
Author(s):  
Pierrette Maes ◽  
Annie Ricouart ◽  
Emmanuel Escher ◽  
André Tartar ◽  
Christian Sergheraert
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Angiotensin Ii ◽  
Solid Phase ◽  
Rabbit Aorta ◽  
Phase Method ◽  
Solid Phase Method

Analogs of angiotensin II in which phenylalanine in position 8 was replaced with cymantrenylalanine or with its triphenylphosphine photosubstitution product were synthesized by the solid-phase method. On rabbit aorta strips, these peptides were found to be pure antagonists of angiotensin II. Their relative affinities are higher than most other analogs substituted in position 8 with bulky amino-acids.

The 1- and 2-Naphthylalanine Analogs of Oxytocin and Vasopressin

1995 ◽  
Vol 60 (12) ◽  
pp. 2170-2177 ◽  
Author(s):  
Zdenko Procházka ◽  
Jiřina Slaninová
Keyword(s):  
Amino Acids ◽  
Solid Phase ◽  
Pressor Test

Solid phase technique on p-methylbenzhydrylamine resin was used for the synthesis of four analogs of oxytocin and four analogs of vasopressin with the non-coded amino acids L- or D- and 1- or 2-naphthylalanine and D-homoarginine. [L-1-Nal2]oxytocin, [D-1-Nal2]oxytocin, [L-2-Nal2]oxytocin, [D-2-Nal2]oxytocin, [L-1-Nal2, D-Har8]vasopressin, [D-1-Nal2, D-Har8]vasopressin, [L-2-Nal2, D-Har8]vasopressin and [D-2-Nal2, D-Har8]vasopressin were synthesized. All eight analogs were found to be uterotonic inhibitors in vitro and in vivo. Analogs with 2-naphthylalanine are stronger inhibitors, particularly in the vasopressin series than the analogs with 1-naphthylalanine. Analogs with 1-naphthylalanine have no activity in the pressor test, analogs with 2-naphthylalanine are weak pressor inhibitors.

[MeArg1, NLe10]-apelin-12: Optimization of solid-phase synthesis and evaluation of biological properties in vitro and in vivo

Peptides ◽  
2020 ◽  
Vol 129 ◽  
pp. 170320 ◽  
Author(s):  
Maria Sidorova ◽  
Irina Studneva ◽  
Valery Bushuev ◽  
Marina Pal’keeva ◽  
Alexander Molokoedov ◽  
...  
Keyword(s):  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Biological Properties ◽  
Phase Synthesis

Conjugates of Hepatitis B Surface Antigen (14-32)Pre-S2 Region with N-Acetylmuramic Acid, N-Acetylnormuramic Acid, and Their L-Alanyl-D-Isoglutamine Derivatives: Synthesis and Studies on Immunogenicity

1992 ◽  
Vol 57 (1) ◽  
pp. 204-211
Author(s):  
Zbigniev Maćkiewicz ◽  
Hanna Świderska ◽  
Maria Kalmanowa ◽  
Zygfryd Smiatacz ◽  
Adam Nowosławski ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Solid Phase ◽  
Hepatitis B Surface Antigen ◽  
Phase Method ◽  
Virus Surface ◽  
Solid Phase Method ◽  
Cellular And Humoral Immunity ◽  
Cellular Immune

Four novel analogs of hepatitis B virus surface antigen (14-32)Pre-S2 region fragment attached covalently to N-acetylmuramic acid, N-acetylmuramyl-L-alanyl-D-isoglutamine, N-acetylnormuramic acid, and N-acetylnormuramyl-L-alanyl-D-isoglutamine were synthesized by the solid phase method. The ability of analogs to induce cellular and humoral immunity to native HBsAg was tested on rabbits. Cellular immune response occurred in vitro, and HBs antibodies were detected in all immunized animals. No additional adjuvants were used in the tests.

Synthese eines Thymosin β10-Fragments zur Entwicklung spezifischer Antikörper / Synthesis of a Fragment of Thymosin β10 for the Development of Specific Antibodies

1992 ◽  
Vol 47 (8) ◽  
pp. 1170-1174 ◽  
Author(s):  
Susanne Hörger ◽  
Brigitte Gallert ◽  
Hartmut Echner ◽  
Wolfgang Voelter
Keyword(s):  
Amino Acids ◽  
Solid Phase ◽  
Protecting Groups ◽  
Side Chain ◽  
Phase Method ◽  
Preparative Hplc ◽  
Specific Antibodies ◽  
Tert Butyl ◽  
Thymosin Β10 ◽  
Solid Phase Method

The N-terminal fragment 1-12 of thymosin β10 was synthesized by the solid phase method using p-benzyloxybenzyl alcohol/polystyrene/divinylbenzeneresin and N-a-Fmoc amino acids with tert-butyl or Boc side chain protecting groups. Coupling was performed with BOP. The peptide was purified by preparative HPLC.

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