scholarly journals Mutations of ovine and bovine placental lactogens change, in different ways, the biological activity mediated through homologous and heterologous lactogenic receptors

2001 ◽  
Vol 169 (1) ◽  
pp. 43-54 ◽  
Author(s):  
D Helman ◽  
A Herman ◽  
J Paly ◽  
O Livnah ◽  
PA Elkins ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Biological Activity ◽  
Biological Activities ◽  
Prolactin Receptor ◽  
The Novel ◽  
Placental Lactogens ◽  
Minimal Time ◽  
The Difference ◽  
Almost All

The biological activities of ovine (o) and bovine (b) placental lactogens (PLs) and their mutated analogues were compared using several binding and in vitro bioassays. In almost all cases, the biological activities of these analogues mediated through rat (r) prolactin receptor (PRLR) showed little or no change, despite a remarkable decrease in their capacity to bind to the extracellular domain of rPRLR and despite compromised stability of the 2:1 complexes. These results indicate that mutations impairing the ability of oPL or bPL to form stable complexes with lactogenic receptors do not necessarily lead to a decrease in the biological activity, because the transient existence of the homodimeric complex is still sufficient to initiate the signal transduction. In contrast, oPL and bPL analogues completely, or almost completely, lost their ability to activate homologous PRLRs, and some of them even acted as site-2 antagonists. To explain the difference between the activity transduced through homologous and that transduced through heterologous PRLRs, we propose the novel term 'minimal time of homodimer persistence'. This concept assumes that in order to initiate the signal transduction, the associated kinase JAK2 has to be transphosphorylated and this requires a 'minimal time' of homodimer existence. In the case of homologous interaction between ruminant PLs and homologous PRLRs, this 'minimal time' is met, though the interaction with homologous PRLRs has a shorter half-life than that with heterologous PRLRs. Therefore oPL or bPL are active in cells possessing both homologous and heterologous PRLRs. Mutations of oPL or bPL lead to reduced affinity and, consequently, the 'time of homodimer persistence' is shortened. Although in the case of heterologous interaction the 'minimal time' is still sufficient to initiate the biological activity, in homologous interactions, which are already weaker than heterologous interactions, further destabilization of the complex shortens its persistence to below the 'minimal time', leading to full or partial loss of biological activity.

Design, synthesis and biological activities of pyrrole-3-carboxamide derivatives as EZH2 (enhancer of zeste homologue 2) inhibitors and anticancer agents

2020 ◽  
Vol 44 (6) ◽  
pp. 2247-2255
Author(s):  
Qifan Zhou ◽  
Lina Jia ◽  
Fangyu Du ◽  
Xiaoyu Dong ◽  
Wanyu Sun ◽  
...  
Keyword(s):  
Biological Activity ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Activity Assay ◽  
Design Synthesis ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Enhancer Of Zeste

A novel series of pyrrole-3-carboxamides targeting EZH2 have been designed and synthesized. The structure–activity relationships were summarized by combining with in vitro biological activity assay and docking results.

scholarly journals Biological activity of the red alga Laurencia brandenii

2011 ◽  
Vol 70 (1) ◽  
pp. 81-90 ◽  
Author(s):  
Aseer Manilal ◽  
Sugathan Sujith ◽  
Balu Sabarathnam ◽  
George Kiran ◽  
Joseph Selvin ◽  
...  
Keyword(s):  
Biological Activity ◽  
Biological Activities ◽  
Sitophilus Oryzae ◽  
Red Alga ◽  
Culture Collection ◽  
Gas Chromatography Mass Spectrometry ◽  
Human Pathogens ◽  
Active Fraction ◽  
Renewable Natural Resource

Biological activity of the red algaLaurencia brandeniiThe marine red algaLaurencia brandeniicollected from the southwest coast of India (Indian Ocean) was extracted and fractioned using column chromatography. The individual fractions were evaluatedin vitrovia antimicrobial activity against six species of Microbial Type Culture Collection and three species of clinical human pathogens, antipest activity onSitophilus oryzae, maggoticidal activity against 2ndinstar larvae ofSarcophagasp. and termiticidal activity againstMicrotermes obesi.It was found that the fraction eluted using petroleum ether:chloroform (6:4) exhibited broader biological activities. The phyco-constituents of the active fraction were identified by gas chromatography-mass spectrometry (GC-MS) analysis. The GC-MS profile of the active fraction revealed that the main constituent was octadecadienoic acid (49.75%) followed by n-hexadecanoic acid (14.24%), which might have a functional role in the biological activities. The overall activity profile envisages that these bioactive compounds fromL. brandeniicould be utilized as a renewable natural resource for the development of novel environmental-compatible formulations for the control of human pathogens, pests, termites and maggots.

scholarly journals Biological activities of recombinant chicken leptin C4S analog compared with unmodified leptins

2000 ◽  
Vol 279 (1) ◽  
pp. E116-E123 ◽  
Author(s):  
S. Dridi ◽  
N. Raver ◽  
E. E. Gussakovsky ◽  
M. Derouet ◽  
M. Picard ◽  
...  
Keyword(s):  
Biological Activity ◽  
Food Intake ◽  
Leptin Receptor ◽  
Biological Activities ◽  
Wild Type ◽  
Escherichia Coli Cells ◽  
Prokaryotic Expression Vector ◽  
Long Form

The chicken leptin sequence, in contrast to mammalian leptins, contains an unpaired Cys at position 3 of the original cDNA ( AF012727 ). The presence of an extra Cys may confer a different structure and affect the leptin's biological activity. To address this, we studied the effects of wild-type and mutated (C4S) chicken leptins in vitro and in vivo and compared them with mammalian leptin prepared from ovine leptin cDNA. The prokaryotic expression vector pMON, encoding full-size A(−1) chicken leptin ( AF012727 ), was mutated using a mutagenesis kit, yielding the C4S analog. Escherichia coli cells transformed with this vector overexpressed large amounts of chicken leptin C4S upon induction with nalidixic acid. The expressed protein, found in the inclusion bodies, was refolded and purified to homogeneity on a Q-Sepharose column, yielding three electrophoretically pure fractions, eluted from the column by 100, 125, and 150 mM NaCl, respectively. All three fractions showed a single band of the expected molecular mass (16 kDa) and were composed of >95% monomeric protein. Proper refolding was evidenced by comparing the circular dichroism spectrum of the analog with spectra of nonmutated chicken and ovine leptins. The biological activity of the C4S analog was evidenced by its ability to stimulate proliferation of leptin-sensitive BAF/3 cells transfected with a long form of human leptin receptor construct similar to its nonmutated counterpart, indicating that Cys4 plays no role in leptin activity. The in vitro activity of both wild-type and mutated chicken leptins was ∼10-fold lower than that of ovine leptin. After intravenous or intraperitoneal injections, C4S analog and the nonmutated chicken and ovine leptins all lowered the food intake of starved 9-day-old broiler or 5-wk-old layer male chickens by 11–34%. Monitoring food behavior revealed that the attenuated food intake resulted not from a decreased number of approaches to the feeders but from a decrease in the average time spent eating during each approach.

Biological characterization of charge isomers of human growth hormone

1988 ◽  
Vol 118 (1) ◽  
pp. 14-21 ◽  
Author(s):  
A. Skottner ◽  
A. Forsman ◽  
B. Skoog ◽  
J. L. Kostyo ◽  
C. M. Cameron ◽  
...  
Keyword(s):  
Biological Activity ◽  
Biological Activities ◽  
Human Growth ◽  
Proteolytic Processing ◽  
Biological Characterization ◽  
Growth Promoting ◽  
Rat Adipose Tissue ◽  
Insulin Like Activity

Abstract. Since deamidation of the human GH molecule may alter the manner and extent to which the hormone is cleaved by proteases, and since it has been repeatedly suggested that proteolytic processing is required for the expression of certain of the activities of GH, the present study was conducted to determine whether the biological activity profiles of more acidic forms of human GH are altered. Three charge isomers, GH-b, GH-c and GH-d, representing primarily deamidated forms, were isolated from a native human GH preparation (Crescormon®) in amounts adequate for characterization of their biological activities. All three were essentially equipotent in a radioimmunoassay for human GH. When assessed for growth-promoting activity in the hypophysectomized rat, the isomers were again equipotent with each other and with the GH preparation from which they were derived. The charge isomers also had significant in vitro insulin-like activity on isolated rat adipose tissue and diabetogenic activity in the ob/ob mouse. Thus, the biological activity profiles of these charge isomers of human GH do not differ greatly from one another.

Synthesis and Activity of New Epipolythiopiperazine-2,5-dione Compounds. I.

1993 ◽  
Vol 46 (11) ◽  
pp. 1743 ◽  
Author(s):  
H Jiang ◽  
N Newcombe ◽  
P Sutton ◽  
QH Lin ◽  
A Mullbacher ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Biological Activity ◽  
Parent Compound ◽  
Reduced Form ◽  
Fungal Toxin ◽  
Naked Dna ◽  
Almost All ◽  
New Compounds ◽  
Proliferation In Vitro

The new lipophilic epipolythiopiperazine-2,5-diones 1,4-dibutylepidithiopiperazine-2,5-dione. 1,4-dibenzylepidithiopiperazine-2,5-dione, 1-benzyl-4-methylepidithiopiperazine-2,5-dione and 3,3′-dithiobis(1,4-dimethylpiperazine-2,5-dione) were synthesized. Unlike the parent compound, the fungal toxin and immunomodulating agent gliotoxin, these compounds did not affect macrophage adherence and cell proliferation in vitro. Like the reduced form of gliotoxin and other simple analogues, these new compounds induce oxidative damage to naked DNA. We conclude that an increase in lipophilicity plays no part in the biological activity of these compounds and in fact abrogates almost all activity. We also synthesized an intermolecular disulfide analogue which also lacked activity.

Cannabis Phenolics and their Bioactivities

2018 ◽  
Vol 25 (10) ◽  
pp. 1160-1185 ◽  
Author(s):  
Federica Pollastro ◽  
Alberto Minassi ◽  
Luigia Grazia Fresu
Keyword(s):  
Biological Activity ◽  
Phenolic Compounds ◽  
Cannabis Sativa ◽  
Biological Activities ◽  
Bibliographic Databases ◽  
Systematic Research ◽  
Prenylated Flavonoids ◽  
Beneficial Effects ◽  
Almost All

Background: Although Cannabis sativa L. is one of the most versatile plant species with multipurpose use both as medical, alimentary source and as psychoactive abuse, its biomedical relevance focused the attention on major cannabinoids. Phytochemical characterization of cannabis highlights the presence of various non-cannabinoids constituents including flavonoids, spiroindans, dihyrostilbenes, dihydrophenanthrenes, lignanamides, steroids and alkaloids. This review aims to identify polyphenols present in this plant, their biosynthesis, their bioactivities and their synthesis, when this occurred. Methods: We undertook a systematic research focused on bibliographic databases including all noncannabinoids phenolics in various C. sativa strains from their isolation, structural elucidation, their biological activity to their synthesis. Result: Nevertheless, attention has so far been focused only on cannabinoids (more than one hundred isolated), cannabis is a complex plant able to produce more than 480 chemical entities that represent almost all of the different biogenetic classes. Regarding phenolic compounds, the plant biosynthesises a plethora of unique non-cannabinoids second metabolites, such as prenylated flavonoids, stilbenoids derivatives and lignanammides. Conclusion: Cannabis is a plant with high pharmacological and nutrition values, its potentialities and applications are not only circumscribed to cannabinoids biological activities, but also defined by noncannabinoid compounds. The combination of other cannabinoids together with noncannabinoid components could enhance the beneficial effects of THC and could reduce undesirable side effects.

scholarly journals Coordination Compounds of Platinum and Palladium with Mixed Ligands (Usnic Acid and 1-(o-Tolyl) Biguanide) � Synthesis, Spectral Characterization and Biological Activity

2020 ◽  
Vol 71 (4) ◽  
pp. 336-346
Author(s):  
Mirela Calinescu ◽  
Ovidiu Oprea ◽  
Catalina Stoica ◽  
Mihai Nita-Lazar ◽  
Madalina Mihalache
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Biological Activity ◽  
Coordination Compounds ◽  
Antitumor Agents ◽  
Biological Activities ◽  
Usnic Acid ◽  
Biological Properties ◽  
Mixed Ligands

Four coordination compounds of Pd(II), Pt(II) and Pt(IV) with usnic acid (H3AU) and 1-(o-tolyl)biguanide (TB) as ligands have been synthesized in view of their potential as antimicrobial, antifungal and antitumor agents. The metal complexes have been characterized by elemental and thermogravimetrical analyses, infrared and electronic spectra. Based on these studies, the following formulas have been proposed for the complexes: [Pd(TB)(H3AU)]PdCl4 (C1), [Pd(TB)(H2AU)] CH3COO (C2), [Pt(TB)(H2AU)Cl2]Cl (C3) and [Pt(TB)(H2AU)]Cl (C4), where H2AU is deprotonated usnic acid. The in vitro biological activities of the new complexes were tested against Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 10231 and HeLa tumor cells. All complexes were found to have good biological properties and therefore they can be further explored in therapeutic applications.

scholarly journals Effect of the Plastein Reaction in Presence of Extrinsic Amino Acids on the Protective Activity of Casein Hydrolysate against Ethanol-Induced Damage in HHL-5 Cells

Foods ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 112
Author(s):  
Li-Ying Bo ◽  
Jia-Nan Pang ◽  
Chun-Li Song ◽  
Tie-Jing Li
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Treatment Time ◽  
Biological Activities ◽  
Casein Hydrolysate ◽  
Protective Activity ◽  
Potential Health ◽  
Plastein Reaction ◽  
Casein Hydrolysates

Casein hydrolysates (CH) were prepared using papain and modified by the plastein reaction (CH-P) in the presence of extrinsic phenylalanine (CH-P-Phe) or tryptophan (CH-P-Trp). The in vitro protective activity of CH and its modified products against ethanol-induced damage in HHL-5 cells was investigated. The results showed that the modification by the plastein reaction reduced the amino group content of CH. However, the modification by the plastein reaction in the presence of extrinsic amino acids could enhance the antioxidant, proliferative, cell cycle arresting, and anti-apoptosis activity of CH. Biological activities of CH and its modified products in the HHL-5 cells varied depending on the hydrolysate concentration (1, 2, and 3 mg/mL) and treatment time (24, 48, and 72 h). Generally, higher biological activities were found after cell treatment with CH or its modified products at concentration of 2 mg/mL for 48 h compared to other treatments. In addition, CH modified in the presence of tryptophan (CH-P-Trp) showed higher biological activity than that modified in the presence of phenylalanine (CH-P-Phe). Based on the obtained results, it can be concluded that casein hydrolysates with enhanced biological activity and potential health benefits can be produced by papain and the plastein reaction with the incorporation of extrinsic amino acids.

scholarly journals Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5226
Author(s):  
Yi-Fei Gu ◽  
Yue Zhang ◽  
Feng-li Yue ◽  
Shao-tong Li ◽  
Zhuo-qi Zhang ◽  
...  
Keyword(s):  
Biological Activities ◽  
Collagen Type I ◽  
Type I ◽  
The Novel ◽  
Pyrimidine Derivatives ◽  
Wide Range ◽  
Ic50 Values ◽  
Privileged Structures ◽  
Pyrimidine Moiety

A pyrimidine moiety exhibiting a wide range of pharmacological activities has been employed in the design of privileged structures in medicinal chemistry. To prepare libraries of novel heterocyclic compounds with potential biological activities, a series of novel 2-(pyridin-2-yl) pyrimidine derivatives were designed, synthesized and their biological activities were evaluated against immortalized rat hepatic stellate cells (HSC-T6). Fourteen compounds were found to present better anti-fibrotic activities than Pirfenidone and Bipy55′DC. Among them, compounds ethyl 6-(5-(p-tolylcarbamoyl)pyrimidin-2-yl)nicotinate (12m) and ethyl 6-(5-((3,4-difluorophenyl)carbamoyl)pyrimidin-2-yl)nicotinate (12q) show the best activities with IC50 values of 45.69 μM and 45.81 μM, respectively. Furthermore, the study of anti-fibrosis activity was evaluated by Picro-Sirius red staining, hydroxyproline assay and ELISA detection of Collagen type I alpha 1 (COL1A1) protein expression. Our study showed that compounds 12m and 12q effectively inhibited the expression of collagen, and the content of hydroxyproline in cell culture medium in vitro, indicating that compounds 12m and 12q might be developed the novel anti-fibrotic drugs.

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