Synthesis and properties of analogues of vasopressin with 1-aminocyclopropane-1-carboxylic acid in position 9

1988 ◽  
Vol 53 (11) ◽  
pp. 2604-2616 ◽  
Author(s):  
Zdenko Procházka ◽  
Juris E. Ancans ◽  
Jiřina Slaninová ◽  
Alena Machová ◽  
Tomislav Barth ◽  
...  
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Nmr Spectroscopy ◽  
Carboxylic Acid ◽  
Arginine Vasopressin ◽  
Solid Phase ◽  
Biological Activities ◽  
Solution Conformation ◽  
Lysine Vasopressin ◽  
C Nmr

Solid phase methodology on benzhydrylamine resin was used for the synthesis of three analogues of vasopressin with non-coded amino acid, 1-aminocyclopropane 1-carboxylic acid, in position 9. Two analogues of lysine-vasopressin ([Lys8, Acc9]vasopressin (I) and Gly3-[Lys8, Acc9]vasopressin (II)) and one analogue of arginine-vasopressin ([Arg8, Acc9]vasopressin (III)) have been synthesized. The dubious value of the biological activity of [Lys8, D-Ala9]vasopressin was reevaluated and [Lys8, L-Ala9]vasopressin was also synthesized and tested for the comparison. Differences in solution conformation of these two analogues were studied by 1H and 13C NMR spectroscopy. Biological activities of all analogues were either significantly lowered or almost completely eliminated. Analogues I-III were found to be completely inactive in analgesia and the CNS activities tested (active and passive avoidance).

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.

The mechanism of formation of 2,7-dimethyl-2,6-octadiene in the synthesis of 3-methylene-7-methyl-1,6-octadiene

1983 ◽  
Vol 48 (7) ◽  
pp. 1864-1866
Author(s):  
Jan Bartoň ◽  
Ivan Kmínek
Keyword(s):  
Mass Spectrometry ◽  
Nmr Spectroscopy ◽  
Alkali Metal ◽  
Chromatographic Analysis ◽  
Solid Phase ◽  
Reaction Pathway ◽  
Mechanism Of Formation ◽  
Gas Chromatographic Analysis ◽  
C Nmr ◽  
Visual Observations

2,7-Dimethyl-2,6-octadiene is formed in the catalytic solution for the dimerization of 2-methyl-1,3-butadiene to β-myrcene (3-methylene-7-methyl-1,6-octadiene), as revealed by mass spectrometry and 13C NMR spectroscopy. Visual observations together with the results of gas chromatographic analysis of the catalytic solution suggest that the formation of 2,7-dimethyl-2,6-octadiene is associated with the transition of the alkali metal (sodium) from the solid phase into the solution. A reaction pathway is suggested accounting for the formation of 2,7-dimethyl-2,6-octadiene in the system.

Structural studies of digitoxin and related cardenolides by two-dimensional NMR

1990 ◽  
Vol 68 (2) ◽  
pp. 272-277 ◽  
Author(s):  
Torbjörn Drakenberg ◽  
Peter Brodelius ◽  
Deane D. McIntyre ◽  
Hans J Vogel
Keyword(s):  
Nmr Spectroscopy ◽  
Nmr Spectra ◽  
Chair Conformation ◽  
Coupling Constants ◽  
Two Dimensional ◽  
Structural Studies ◽  
Solution Conformation ◽  
Phase Sensitive ◽  
Multiple Relay ◽  
C Nmr

The 1H and 13C NMR spectra of the cardenolides digitoxigenin, digoxigenin, digitoxin, and mono- and bis-digitoxigenin digitoxosides have been completely assigned by two-dimensional NMR spectroscopy. The techniques used include phase-sensitive COSY, multiple relay COSY, and carbon–proton correlation (HETCOR and HMQC) spectra. Various aspects of the solution conformation of the steroid moiety of digitoxin and digoxigenin could be determined from coupling constants and NOE difference experiments and they are indicative of an all-chair conformation. The carbohydrate rings in digitoxin and the mono- and bis-digitoxigenin digitoxosides are also in the chair conformation. Keywords: cardenolides, digitoxigenin, digitoxin, 2-dimensional NMR, conformational analysis.

(S)-2,2,5,5-Tetramethylthiazolidine-4-carboxylic acid: a compound which exists in the amino acid rather than the zwitterion form

1985 ◽  
Vol 63 (9) ◽  
pp. 2411-2419 ◽  
Author(s):  
Helen Elaine Howard-Lock ◽  
Colin James Lyne Lock ◽  
Philip Stuart Smalley
Keyword(s):  
Amino Acid ◽  
Carboxylic Acid ◽  
Raman Spectra ◽  
Cooh Group ◽  
Infrared And Raman Spectra ◽  
Acid Form ◽  
Hydrogen Atoms ◽  
Cell Dimensions ◽  
Amino Acid Form ◽  
C Nmr

The X-ray crystal structure of (S)-2,2,5,5-tetramethylthiazolidine-4-carboxylic acid, 1, has been determined. Crystals are monoclinic, P21, with cell dimensions a = 11.351(4) b = 8.303(2), c = 11.969(3) Å, β = 116.69(2)°, and Z = 4. The structure was solved by standard methods and refined to R1 = 0.0774, R2 = 0.0670 for 2388 independent reflections. Compound 1 exists in the amino-acid form as shown by two distinctly different C—O bond lengths, 1.209 and 1.309 Å, typical of the COOH group, and by the positions of the hydrogen atoms. The amino-acid form of 1 found in the solid also exists in solution as shown by infrared and Raman spectra. The mass spectra, and 1H and 13C nmr spectra are reported, as well as detailed infrared and Raman spectra for the title compound and several deuterated species.

scholarly journals Effects of Dimerization on the Structure and Biological Activity of Antimicrobial Peptide Ctx-Ha

2012 ◽  
Vol 56 (6) ◽  
pp. 3004-3010 ◽  
Author(s):  
E. N. Lorenzón ◽  
G. F. Cespedes ◽  
E. F. Vicente ◽  
L. G. Nogueira ◽  
T. M. Bauab ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Biological Activity ◽  
Antimicrobial Peptide ◽  
Hemolytic Activity ◽  
Pore Diameter ◽  
Solid Phase ◽  
Biological Activities ◽  
Solid Phase Peptide Synthesis ◽  
Activity Assay ◽  
Growth Of Bacteria

ABSTRACTIt is well known that cationic antimicrobial peptides (cAMPs) are potential microbicidal agents for the increasing problem of antimicrobial resistance. However, the physicochemical properties of each peptide need to be optimized for clinical use. To evaluate the effects of dimerization on the structure and biological activity of the antimicrobial peptide Ctx-Ha, we have synthesized the monomeric and three dimeric (Lys-branched) forms of the Ctx-Ha peptide by solid-phase peptide synthesis using a combination of 9-fluorenylmethyloxycarbonyl (Fmoc) andt-butoxycarbonyl (Boc) chemical approaches. The antimicrobial activity assay showed that dimerization decreases the ability of the peptide to inhibit growth of bacteria or fungi; however, the dimeric analogs displayed a higher level of bactericidal activity. In addition, a dramatic increase (50 times) in hemolytic activity was achieved with these analogs. Permeabilization studies showed that the rate of carboxyfluorescein release was higher for the dimeric peptides than for the monomeric peptide, especially in vesicles that contained sphingomyelin. Despite different biological activities, the secondary structure and pore diameter were not significantly altered by dimerization. In contrast to the case for other dimeric cAMPs, we have shown that dimerization selectively decreases the antimicrobial activity of this peptide and increases the hemolytic activity. The results also show that the interaction between dimeric peptides and the cell wall could be responsible for the decrease of the antimicrobial activity of these peptides.

THE DEVELOPMENT OF A RADIOIMMUNOASSAY FOR OXYTOCIN: SENSITIVITY OF THE ASSAY IN AQUEOUS BUFFER SOLUTION, SPECIFICITY AND THE DISSOCIATION OF IMMUNOLOGICAL AND BIOLOGICAL ACTIVITY

1970 ◽  
Vol 46 (4) ◽  
pp. 533-542 ◽  
Author(s):  
T. CHARD ◽  
M. L. FORSLING ◽  
M. A. R. JAMES ◽  
M. J. KITAU ◽  
J. LANDON
Keyword(s):  
Aqueous Solution ◽  
Biological Activity ◽  
Arginine Vasopressin ◽  
Late Pregnancy ◽  
Reducing Agents ◽  
Immunological Activity ◽  
Buffer Solution ◽  
Aqueous Buffer ◽  
Lysine Vasopressin ◽  
Other Substances

SUMMARY A radioimmunoassay for oxytocin in aqueous solution is described, with a sensitivity comparable with the best current bioassays. It is highly specific; arginine-vasopressin and lysine-vasopressin interfere only at 1000-fold greater concentration, while bradykinin, histamine, acetycholine and many other substances, which interfere with some bioassays, have no effect. In certain circumstances, there is a dissociation between loss of biological and immunological activity. Thus reducing agents had no effect on immunological activity, in contrast to their effect on biological activity. In late pregnancy plasma, the biological activity of oxytocin is destroyed more rapidly than the immunological activity. Radioimmunoassays have considerable advantages over bioassays both in convenience and specificity. However, bioassays should be employed for reference purposes because of the dissociation between biological and immunological activity that may occur.

A comparison of the inhibitory effects of somatostatin-14, -25, and -28 on motility of the guinea pig ileum

1986 ◽  
Vol 64 (3) ◽  
pp. 303-306 ◽  
Author(s):  
Christopher H. S. McIntosh ◽  
Victoria Bakich ◽  
Yin Nam Kwok ◽  
John C. Brown
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Guinea Pig ◽  
Biological Activities ◽  
Threshold Concentration ◽  
Inhibitory Effects ◽  
Guinea Pig Ileum ◽  
Maximal Inhibition ◽  
Acid Fragment ◽  
Somatostatin 14

A number of studies have suggested that somatostatin-14 (SS-14) and somatostatin-28 (SS-28) exhibit a similar spectrum of biological activities but have different potencies. In the present study the effects of SS-14, SS-28, and somatostatin-25 on electrically induced contractions of the guinea pig ileum have been compared. All three peptides exhibited equipotent inhibitory effects. Inhibition was obtained at a threshold concentration less than 10−10 M, with maximal inhibition at 10−7 M and IC50 values of 6.0–6.5 × 10−10 M. The N-terminal 14 amino acid fragment of SS-28 had no effect either on motility, when added alone, or on the actions of SS-28, suggesting that this region of the molecule is not critical for biological activity.

Synthesis and properties of oxytocin analogues modified in the tripeptide side chain

1984 ◽  
Vol 49 (3) ◽  
pp. 642-652 ◽  
Author(s):  
Zdenko Procházka ◽  
Michal Lebl ◽  
Tomislav Barth ◽  
Jan Hlaváček ◽  
Antonín Trka ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Carboxylic Acid ◽  
Biological Activities ◽  
The Other ◽  
Side Chain ◽  
H Nmr ◽  
Fragment Condensation

Two oxytocin analogues were synthesized by fragment condensation (6 + 3) in the presence of dicyclohexylcarbodiimide and 1-hydroxybenzotriazole. In one of the analogues, proline in the position 7 and leucine in the position 8 were substituted by 2-[1-(2-oxo-3-aminopyrrolidinyl)]-4-methylpentanoic acid, in the other proline was replaced by 1-aminocyclopropane-1-carboxylic acid. Biological activities of the first analogue were strongly reduced and dissociation of the uterotonic and galoctogogic activities was observed with both the analogues. The structure of 2-(3-tert-butyloxycarbonylaminopyrrolidin-2-on-1-yl)-4-methylpentanoylglycine and its amide was confirmed by mass and 1 H NMR spectroscopy.

Conformational and biological analysis of α-MSH fragment analogues with sterically constrained amino acid residues

1988 ◽  
Vol 53 (11) ◽  
pp. 2549-2573 ◽  
Author(s):  
Victor J. Hruby ◽  
Wayne L. Cody ◽  
Ana Maria de Lauro Castrucci ◽  
Mac E. Hadley
Keyword(s):  
Amino Acid ◽  
Carboxylic Acid ◽  
Aromatic Ring ◽  
Biological Activities ◽  
Three Dimensional ◽  
Amino Acid Side Chain ◽  
Nmr Studies ◽  
Peptide Backbone ◽  
Biological Analysis ◽  
Conformational Properties

Conformational and biological analysis of the linear 4-11 fragment analogues, Ac-[Nle4]-α-MSH4-11-NH2 (II) and Ac-[Nle4, D-Phe7]-α-MSH4-11-NH2 (III) and related analogues have been undertaken. In solution, the peptide backbone is flexible, but in the case of D-Phe7 analogues an interaction of the His6, D-Phe7 and Arg8 amino acid side chain groups may be present based on the shielding patterns observed in the proton NMR and on comparison of NT1 values. The importance of the position 7 to the biological and conformational properties was further examined by substitution of either L- or D-phenylglycine (Pgl) or L- and D-1,2,3,4-tetrahydroisoquinoline carboxylic acid (Tic) for phenylalanine-7. Ac-[Nle4, Pgl7]-α-MSH4-11-NH2 (IV), Ac-[Nle4, D-Pgl7]-α-MSH4-11-NH2 (V), Ac-[Nle4, Tic7]-α-MSH4-11-NH2 (VI), and Ac-[Nle4, D-Tic7]-α-MSH4-11-NH2 (VII) were prepared. These substituted analogues were examined for their biological activities and conformational properties with emphasis on the three-dimensional orientation of the aromatic ring in the position 7, and the effects of the aromatic ring on adjacent amino acids, and on biological activities. The relative potencies of the analogues in the frog skin assay system were: II (1·00); III (118); IV (82·4); V (0·18); VI (0·18); and VII (0·14); and in the lizard skin bioassay they were: II (1·00); III (10·0); IV (0·14); V (0·005); VI (0·00025); and VII (0·01). On the basis of the NMR studies the L-phenylglycine substitution results in an enhanced ring stacking interaction between the phenyl ring of Pgl7 and the indole ring of Trp9. The 1,2,3,4-tetrahydroisoquinoline carboxylic acid (Tic) substitution leads to significant backbone restriction and an interaction of the alpha proton of His6 with the carbonyl of Glu5. The possible relationships of these effects to biological activity are discussed.

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