scholarly journals Oxytocin analogues with amide groups substituted by tetrazole groups in position 4, 5 or 9.

2007 ◽  
Vol 54 (4) ◽  
pp. 805-811 ◽  
Author(s):  
Michał Manturewicz ◽  
Zbigniew Grzonka ◽  
Lenka Borovicková ◽  
Jirina Slaninová
Keyword(s):  
Amino Acids ◽  
Solid Phase ◽  
Biological Activities ◽  
Synthesis Method ◽  
Oxytocin Receptor ◽  
Amide Group ◽  
Biologically Active ◽  
Side Chain ◽  
Electronic Effects

Eleven oxytocin analogues substituted in position 4, 5 or 9 by tetrazole analogues of amino acids were prepared using solid-phase peptide synthesis method and tested for rat uterotonic in vitro and pressor activities, as well as for their affinity to human oxytocin receptor. The tetrazolic group has been used as a bioisosteric substitution of carboxylic, ester or amide groups in structure-activity relationship studies of biologically active compounds. Replacement of the amide groups of Gln(4) and Asn(5) in oxytocin by tetrazole analogues of aspartic, glutamic and alpha-aminoadipic acids containing the tetrazole moiety in the side chains leads to analogues with decreased biological activities. Oxytocin analogues in which the glycine amide residue in position 9 was substituted by tetrazole analogues of glycine had diminished activities as well. The analysis of differences in rat uterotonic activity and in the affinity to human oxytocin receptors of analogues containing either an acidic 5-substituted tetrazolic group or a neutral 1,5- or 2,5-tetrazole nucleus makes it possible to draw some new conclusions concerning the role of the amide group of amino acids in positions 4, 5 and 9 of oxytocin for its activity. The data suggest that the interaction of the side chain of Gln(4) with the oxytocin receptor is influenced mainly by electronic effects and the hydrogen bonding capacity of the amide group. Steric effects of the side chain are minor. Substitution of Asn(5) by its tetrazole derivative gave an analogue of very low activity. The result suggests that in the interaction between the amide group of Asn(5) and the binding sites of oxytocic receptor hydrogen bonds are of less importance than the spatial requirements for this group.

4-THREONINE ANALOGUES OF NEUROHYPOPHYSIAL HORMONES WITH SELECTIVELY ENHANCED OXYTOCIN-LIKE ACTIVITIES

1971 ◽  
Vol 49 (1) ◽  
pp. 151-165 ◽  
Author(s):  
W. H. SAWYER ◽  
M. MANNING
Keyword(s):  
Amino Acids ◽  
Solid Phase ◽  
Biological Activities ◽  
Molecular Structures ◽  
Natural Hormone ◽  
Equal Dose ◽  
Rabbit Milk ◽  
Natural Hormones

SUMMARY The 4-threonine analogues of oxytocin and of mesotocin and isotocin were prepared by solid-phase synthesis. [4-Threonine]-oxytocin is about twice as active as oxytocin in rat uterus assays in vitro and in vivo and about three times as active in fowl vasodepressor assays. It is slightly more active than oxytocin in rat or rabbit milk-ejection assays. When infused intravenously into water-loaded rats it causes much less depression of diuresis than does an equal dose of oxytocin. [4-Threonine]-oxytocin has much less vasopressor activity than oxytocin. [4-Threonine]-mesotocin also shows enhanced oxytocin-like properties. Its oxytocic activity is equal to or greater than that of oxytocin and its fowl vasodepressor potency is about the same as that of [4-threonine]-oxytocin, 1500 u./mg. It also has less antidiuretic and vasopressor activities than mesotocin. Thus 4-threonine analogues, containing nothing but common l-amino acids, appear to have more of the specific oxytocin-like properties and less of the vasopressin-like properties than do oxytocin or mesotocin. Thus they may be considered improvements on the natural hormones. In this respect they are unique among the reported synthetic analogues of natural peptide hormones. Substitution of 4-threonine in the weakly-active analogue [3-leucine]-oxytocin also increases its oxytocic and fowl vasodepressor activities. Thus a threonine in the 4-position appears to endow oxytocin-like peptides with greater specific activities than do the amino acids that occur naturally in this position, glutamine and serine. These observations may be of interest when considered (a) from an evolutionary viewpoint, (b) in attempting to interpret relations between molecular structures and biological activities, and (c) as describing peptides with more of the desired properties of oxytocin and less of the undesired properties which might have therapeutic advantages over the natural hormone.

Metabolomics of Healthy Berry Fruits

2019 ◽  
Vol 25 (37) ◽  
pp. 4888-4902 ◽  
Author(s):  
Gilda D'Urso ◽  
Sonia Piacente ◽  
Cosimo Pizza ◽  
Paola Montoro
Keyword(s):  
Biological Activities ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Bioactive Metabolites ◽  
Active Metabolites ◽  
Positive Effects ◽  
Cell Functions ◽  
Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

Synthetic Routes for 1,4-disubstituted 1,2,3-triazoles: A Review

2019 ◽  
Vol 23 (8) ◽  
pp. 860-900 ◽  
Author(s):  
Chander P. Kaushik ◽  
Jyoti Sangwan ◽  
Raj Luxmi ◽  
Krishan Kumar ◽  
Ashima Pahwa
Keyword(s):  
Solid Phase ◽  
Click Reaction ◽  
Biological Activities ◽  
Triazole Ring ◽  
Copper Catalysts ◽  
Biologically Active ◽  
Pharmaceutical Chemistry ◽  
Biological Targets ◽  
Synthetic Routes ◽  
High Yields

N-Heterocyclic compounds like 1,2,3-triazoles serve as a key scaffolds among organic compounds having diverse applications in the field of drug discovery, bioconjugation, material science, liquid crystals, pharmaceutical chemistry and solid phase organic synthesis. Various drugs containing 1,2,3-triazole ring which are commonly available in market includes Rufinamide, Cefatrizine, Tazobactam etc., Stability to acidic/basic hydrolysis along with significant dipole moment support triazole moiety for appreciable participation in hydrogen bonding and dipole-dipole interactions with biological targets. Huisgen 1,3-dipolar azide-alkyne cycloaddition culminate into a mixture of 1,4 and 1,5- disubstituted 1,2,3-triazoles. In 2001, Sharpless and Meldal came across with a copper(I) catalyzed regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles by cycloaddition between azides and terminal alkynes. This azide-alkyne cycloaddition has been labelled as a one of the important key click reaction. Click synthesis describes chemical reactions that are simple to perform, gives high selectivity, wide in scope, fast reaction rate and high yields. Click reactions are not single specific reaction, but serve as a pathway for construction of simple to complex molecules from a variety of starting materials. In the last few decades, 1,2,3-triazoles attracted attention of researchers all over the world because of their broad spectrum of biological activities. Keeping in view the biological importance of 1,2,3-triazole, in this review we focus on the various synthetic routes for the syntheisis of 1,4-disubstituted 1,2,3-triazoles. This review involves various synthetic protocols which involves copper and non-copper catalysts, different solvents as well as substrates. It will boost synthetic chemists to explore new pathway for the development of newer biologically active 1,2,3-triazoles.

Analogues of the cholecystokinin octapeptide modified in the central part of the molecule

1991 ◽  
Vol 56 (9) ◽  
pp. 1963-1970 ◽  
Author(s):  
Jan Hlaváček ◽  
Václav Čeřovský ◽  
Jana Pírková ◽  
Pavel Majer ◽  
Lenka Maletínská ◽  
...  
Keyword(s):  
Amino Acid ◽  
Biological Activities ◽  
Point Of View ◽  
Biologically Active ◽  
Side Chain ◽  
Amino Acid Residues ◽  
Cholecystokinin Octapeptide ◽  
Biological Tests ◽  
Biological Potency ◽  
Biologically Active Conformation

In a series of analogues of the cholecystokinin octapeptide (CCK-8) the amino acid residues were gradually modified by substituting Gly by Pro in position 4, Trp by His in position 5, Met by Cle in position 6, or the Gly residue was inserted between Tyr and Met in positions 2 and 3 of the peptide chain, and in the case of the cholecystokinin heptapeptide (CCK-7) the Met residues were substituted by Nle or Aib. These peptides were investigated from the point of view of their biological potency in the peripheral and central region. From the results of the biological tests it follows that the modifications carried out in these analogues and in their Nα-Boc derivatives mean a suppression of the investigated biological activities by 2-3 orders of magnitude (at a maximum dose of the tested substance of 2 . 10-2 mg per animal).This means that a disturbance of the assumed biologically active conformation of CCK-8, connected with a considerable decrease of the biological potency of the molecule, takes place not only after introduction of the side chain into its centre (substitution of Gly4), but also after the modification of the side chains of the amino acids or by extension of the backbone in further positions around this central amino acid.

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.

scholarly journals Pyrrole-Mediated Peptide Cyclization Identified through Genetically Reprogrammed Peptide Synthesis

Biomedicines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 99 ◽  
Author(s):  
Klaas Decoene ◽  
Willem Vannecke ◽  
Toby Passioura ◽  
Hiroaki Suga ◽  
Annemieke Madder
Keyword(s):  
Peptide Synthesis ◽  
Cyclic Peptide ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Screening Method ◽  
In Vitro Translation ◽  
Side Chain ◽  
One Pot ◽  
Depth Analysis

Flexible in vitro translation (FIT) was used as a screening method to uncover a new methodology for peptide constraining based on the attack of a nucleophilic side-chain functionality onto an oxidized furylalanine side chain. A set of template peptides, each containing furylalanine as furan-modified amino acid and a nucleophilic residue (Cys, His, Lys, Arg, Ser, or Tyr), was produced through FIT. The translation mixtures were treated with N-bromosuccinimide (NBS) to achieve selective furan oxidation and subsequent MALDI analysis demonstrated Lys and Ser as promising residues for cyclisation. Solid-phase peptide synthesis (SPPS) was used to synthesize suitable amounts of material for further in-depth analysis and characterisation. It was found that in the case of the peptide containing lysine next to a furylalanine residue, a one-pot oxidation and reduction reaction leads to the generation of a cyclic peptide featuring a pyrrole moiety as cyclisation motif, resulting from the attack of the lysine side chain onto the oxidized furylalanine side chain. Structural evidence was provided via NMR and the generality of the methodology was explored. We hereby expand the scope of our previously developed furan-based peptide labeling and crosslinking strategy.

Preservation of immunological and biological activities of insulin by insulinase inhibitor in vitro

1970 ◽  
Vol 48 (5) ◽  
pp. 291-298
Author(s):  
J. Pierluissi ◽  
J. Campbell ◽  
K. S. Rastogi ◽  
G. R. Green ◽  
V. Lazdins
Keyword(s):  
Biological Effect ◽  
Biological Activities ◽  
Biologically Active ◽  
Immunoreactive Insulin ◽  
Maximal Velocity ◽  
Appreciable Change ◽  
Glycogen Accumulation ◽  
Fractional Rate ◽  
Diaphragm In Vitro

The relation of insulinase activity to the biological effect of insulin on isolated tissue was studied. Rat diaphragm in vitro caused the rapid disappearance of immunoreactive insulin (IRI) in physiological concentrations. IRI loss at time intervals was exponential. The fractional rate of loss of IRI was therefore independent of IRI concentration and was also approximately constant per milligram of tissue, the value being 0.0216%/mg∙mm. The value of the Michaelis constant (Km), obtained from initial velocities at five initial concentrations of IRI, was 1.85 × 10−8M, and of the maximal velocity (Vmax) was 2.32 × 10−11 mole/g∙min, based on insulin dimer. The addition of an insulinase inhibitor (a partial hydrolysate of insulin) to hemidiaphragm in vitro reduced the fractional rate of IRI loss by 60%. The increase in Km, without appreciable change in Vmax, indicated that the inhibition was competitive. The IRI preserved by means of the inhibitor was biologically active, since it increased the glycogen accumulation and the incorporation of 14C-U-glucose into glycogen in a second, fresh hemidiaphragm. In single incubation of hemidiaphragm with insulin, the gain in glycogen was correlated with the amount of inhibitor. The biological effect of insulin on diaphragm in vitro was therefore limited by tissue insulinase activity, and insulinase inhibitor potentiated to some extent the action of insulin.

scholarly journals Phytochemical Characterization and Evaluation of Biological Activities of Egyptian Carob Pods (Ceratonia siliqua L.) Aqueous Extract: In Vitro Study

Plants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 2626
Author(s):  
Wael Sobhy Darwish ◽  
Abada El Sayed Khadr ◽  
Maher Abd El Naby Kamel ◽  
Mabrouk A. Abd Eldaim ◽  
Ibrahim El Tantawy El Sayed ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Biological Activities ◽  
Radical Scavenging ◽  
Antimicrobial Activities ◽  
Biologically Active ◽  
Phytochemical Analysis ◽  
Type I ◽  
Hypotonic Solution ◽  
Ceratonia Siliqua

Ceratonia siliqua (Carob) is an evergreen Mediterranean tree, and carob pods are potentially nutritive and have medicinal value. The present study was carried out to estimate the possible biological activities of phytochemical-characterized carob pod aqueous extract (CPAE). The phytochemical contents of CPAE were determined by using colorimetric methods and HPLC. In addition, the free radical scavenging properties and anti-diabetic, anti-hemolytic, and antimicrobial activities were estimated by using standardized in vitro protocols. The phytochemical analysis revealed that CPAE was rich in polyphenols, flavonoids, and alkaloids, where it contained a significant amount of gallic acid, catechin, and protocatechuic acid. Furthermore, CPAE exhibited strong antioxidant activity where it prevented the formation of 2, 2-Diphenyl-1-picryl hydrazyl, hydroxyl, and nitric oxide free radicals. Additionally, it had a potent inhibitory effect against digestive enzymes (amylase, maltase, sucrase, and lactase). Moreover, CPAE exhibited anti-Staph aureus, anti-Escherichia coli, anti-Candida albicans, and anti-herpes simplex type I virus (HSV-I). Finally, CPAE protected the erythrocyte membrane from hypotonic solution-induced hemolysis. Altogether, CPAE could be regarded as an interesting source of biologically active antioxidant, anti-diabetic, and antimicrobial preparation for a potential application in pharmaceutical and food supplement fields.

scholarly journals Chromatographic Analyses, In Vitro Biological Activities, and Cytotoxicity of Cannabis sativa L. Essential Oil: A Multidisciplinary Study

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3266 ◽  
Author(s):  
Gokhan Zengin ◽  
Luigi Menghini ◽  
Antonella Di Sotto ◽  
Romina Mancinelli ◽  
Francesca Sisto ◽  
...  
Keyword(s):  
Essential Oil ◽  
Galleria Mellonella ◽  
Cannabis Sativa ◽  
Biological Activities ◽  
Methodological Approach ◽  
Volatile Component ◽  
Biologically Active ◽  
Antioxidant Compounds

Due to renewed interest in the cultivation and production of Italian Cannabis sativa L., we proposed a multi-methodological approach to explore chemically and biologically both the essential oil and the aromatic water of this plant. We reported the chemical composition in terms of cannabinoid content, volatile component, phenolic and flavonoid pattern, and color characteristics. Then, we demonstrated the ethnopharmacological relevance of this plant cultivated in Italy as a source of antioxidant compounds toward a large panel of enzymes (pancreatic lipase, α-amylase, α-glucosidase, and cholinesterases) and selected clinically relevant, multidrug-sensible, and multidrug-resistant microbial strains (Staphylococcus aureus, Helicobacter pylori, Candida, and Malassezia spp.), evaluating the cytotoxic effects against normal and malignant cell lines. Preliminary in vivo cytotoxicity was also performed on Galleria mellonella larvae. The results corroborate the use of this natural product as a rich source of important biologically active molecules with particular emphasis on the role exerted by naringenin, one of the most important secondary metabolites.

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