Combined strong anion-exchange HPLC and PAGE approach for the purification of heparan sulphate oligosaccharides

2001 ◽  
Vol 354 (1) ◽  
pp. 141-147 ◽  
Author(s):  
Romain R. VIVÈS ◽  
Sarah GOODGER ◽  
David A. PYE
Keyword(s):  
Anion Exchange ◽  
Biological Activities ◽  
Heparan Sulphate ◽  
Structural Features ◽  
Biological Properties ◽  
Cellular Functions ◽  
Structural Isomers ◽  
Wide Range ◽  
Strong Anion Exchange ◽  
Anion Exchange Hplc

Heparan sulphates are highly sulphated linear polysaccharides involved in many cellular functions. Their biological properties stem from their ability to interact with a wide range of proteins. An increasing number of studies, using heparan sulphate-derived oligosaccharides, suggest that specific structural features within the polysaccharide are responsible for ligand recognition and regulation. In the present study, we show that strong anion-exchange HPLC alone, a commonly used technique for purification of heparan sulphate-derived oligosaccharides, may not permit the isolation of highly pure heparan sulphate oligosaccharide species. This was determined by PAGE analysis of hexa-, octa- and decasaccharide samples deemed to be pure by strong anion-exchange HPLC. In addition, subtle differences in the positioning of sulphate groups within heparan sulphate hexasaccharides were impossible to detect by strong anion-exchange HPLC. PAGE analysis on the other hand afforded excellent resolution of these structural isomers. The precise positioning of specific sulphate groups has been implicated in determining the specificity of heparan sulphate interactions and biological activities; hence, the purification of oligosaccharide species that differ in this way becomes an important issue. In this study, we have used strong anion-exchange HPLC and PAGE techniques to allow production of the homogeneous heparan sulphate oligosaccharide species that will be required for the detailed study of structure/activity relationships.

scholarly journals Novel Trifluoromethyl Pyrimidinone Compounds With Activity Against Mycobacterium tuberculosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Erik Hembre ◽  
Julie V. Early ◽  
Joshua Odingo ◽  
Catherine Shelton ◽  
Olena Anoshchenko ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Major Change ◽  
Structural Features ◽  
Research Area ◽  
Biological Properties ◽  
Pyridyl Ring ◽  
Pyridyl Group ◽  
Gram Positive Bacteria ◽  
Wide Range ◽  
Cytotoxic Molecules

The identification and development of new anti-tubercular agents are a priority research area. We identified the trifluoromethyl pyrimidinone series of compounds in a whole-cell screen against Mycobacterium tuberculosis. Fifteen primary hits had minimum inhibitory concentrations (MICs) with good potency IC90 is the concentration at which M. tuberculosis growth is inhibited by 90% (IC90 < 5 μM). We conducted a structure–activity relationship investigation for this series. We designed and synthesized an additional 44 molecules and tested all analogs for activity against M. tuberculosis and cytotoxicity against the HepG2 cell line. Substitution at the 5-position of the pyrimidinone with a wide range of groups, including branched and straight chain alkyl and benzyl groups, resulted in active molecules. Trifluoromethyl was the preferred group at the 6-position, but phenyl and benzyl groups were tolerated. The 2-pyridyl group was required for activity; substitution on the 5-position of the pyridyl ring was tolerated but not on the 6-position. Active molecules from the series demonstrated low selectivity, with cytotoxicity against eukaryotic cells being an issue. However, there were active and non-cytotoxic molecules; the most promising molecule had an MIC (IC90) of 4.9 μM with no cytotoxicity (IC50 > 100 μM). The series was inactive against Gram-negative bacteria but showed good activity against Gram-positive bacteria and yeast. A representative molecule from this series showed rapid concentration-dependent bactericidal activity against replicating M. tuberculosis bacilli with ~4 log kill in <7 days. Overall the biological properties were promising, if cytotoxicity could be reduced. There is scope for further medicinal chemistry optimization to improve the properties without major change in structural features.

scholarly journals Effect of the Modifications on the Physicochemical and Biological Properties of β-Glucan—A Critical Review

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 57 ◽  
Author(s):  
Hongjie Yuan ◽  
Ping Lan ◽  
Yan He ◽  
Chengliang Li ◽  
Xia Ma
Keyword(s):  
Food Processing ◽  
Triple Helix ◽  
Functional Foods ◽  
Physiological Function ◽  
Biological Activities ◽  
Structural Features ◽  
Biological Properties ◽  
Enzymatic Modification ◽  
Anti Oxidant

β-Glucan exhibits many biological activities and functions such as stimulation of the immune system and anti-inflammatory, anti-microbial, anti-infective, anti-viral, anti-tumor, anti-oxidant, anti-coagulant, cholesterol-lowering, radio protective, and wound healing effects. It has a wide variety of uses in pharmaceutical, cosmetic, and chemical industries as well as in food processing units. However, due to its dense triple helix structure, formed by the interaction of polyhydroxy groups in the β-d-glucan molecule, it features poor solubility, which not only constrains its applications, but also inhibits its physiological function in vivo. One aim is to expand the applications for modified β-glucan with potential to prevent disease, various therapeutic purposes and as health-improving ingredients in functional foods and cosmetics. This review introduces the major modification methods required to understand the bioactivity of β-glucan and critically provides a literature survey on the structural features of this molecule and reported biological activity. We also discuss a new method to create novel opportunities to exploit maximally various properties of β-glucan, namely ultrasound-assisted enzymatic modification.

scholarly journals Characterization of Andean Blueberry in Bioactive Compounds, Evaluation of Biological Properties and in vitro Bioaccessibility

2020 ◽  
Author(s):  
Nieves Baenas ◽  
Jenny Ruales ◽  
Diego A. Moreno ◽  
Daniel Alejandro Barrio ◽  
Carla M. Stinco ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Bioactive Compounds ◽  
Biological Activities ◽  
In Vitro Digestion ◽  
Biological Properties ◽  
Wide Range ◽  
Zebrafish Embryogenesis

Andean blueberries are wild berries grown and consumed in Ecuador which contain high values of bioactive compounds, mainly anthocyanins, with powerful antioxidant activity. The aim of this study was to evaluate the profile and contents of (poly)phenols and carotenoids in Andean blueberry by HPLC-DAD-MSn and determine a wide range of its biological activities. The antioxidant capacity of this fruit was evaluated in vitro by three different methods and in vivo using the zebrafish animal model, also the toxicity effect was determined by the zebrafish embryogenesis test. Besides, the antimicrobial activity and the capacity of Andean blueberry to produce hemagglutination in blood cells were evaluated. Finally, the bioaccessibility of (poly)phenols and related antioxidant capacity were determined in the different phases of an in vitro digestion. The global results indicated no toxicity of Andean blueberry, weakly bacteriostatic activity, and high contents of anthocyanins and antioxidant capacity, which were partially bioaccesible in vitro (~ 50 % at the final intestinal step), contributing to the knowledge of its health benefits for consumers and its potential use in the food and pharmaceutical industry as functional ingredient.

scholarly journals An Overview of Bioactive 1,3-Oxazole-Containing Alkaloids from Marine Organisms

2021 ◽  
Vol 14 (12) ◽  
pp. 1274
Author(s):  
Jinyun Chen ◽  
Sunyan Lv ◽  
Jia Liu ◽  
Yanlei Yu ◽  
Hong Wang ◽  
...  
Keyword(s):  
Nitrogen Atom ◽  
Chemical Synthesis ◽  
Biological Activities ◽  
Structural Features ◽  
Biological Properties ◽  
Therapeutic Agents ◽  
Marine Organisms ◽  
Chemical Structures ◽  
First Time ◽  
Oxazole Derivatives

1,3-Oxazole chemicals are a unique class of five-membered monocyclic heteroarenes, containing a nitrogen atom and an oxygen. These alkaloids have attracted extensive attention from medicinal chemists and pharmacologists owing to their diverse arrays of chemical structures and biological activities, and a series of 1,3-oxazole derivatives has been developed into therapeutic agents (e.g., almoxatone, befloxatone, cabotegravir, delpazolid, fenpipalone, haloxazolam, inavolisib). A growing amount of evidence indicates that marine organisms are one of important sources of 1,3-oxazole-containing alkaloids. To improve our knowledge regarding these marine-derived substances, as many as 285 compounds are summarized in this review, which, for the first time, highlights their sources, structural features and biological properties, as well as their biosynthesis and chemical synthesis. Perspective for the future discovery of new 1,3-oxazole compounds from marine organisms is also provided.

scholarly journals Kefiran biopolymer: Evaluation of its physicochemical and biological properties

2018 ◽  
Vol 33 (5) ◽  
pp. 461-478 ◽  
Author(s):  
Hajer Radhouani ◽  
Cristiana Gonçalves ◽  
Fátima R Maia ◽  
Joaquim M Oliveira ◽  
Rui L Reis
Keyword(s):  
Molecular Weight ◽  
Photoelectron Spectroscopy ◽  
Average Molecular Weight ◽  
Structural Features ◽  
Biological Properties ◽  
Health Claims ◽  
Extrusion Force ◽  
Wide Range ◽  
Physicochemical And Biological Properties ◽  
Kefir Grains

Kefiran, an exopolysaccharide produced by lactic acid bacteria, has received a great interest due to a variety of health claims. In this study, we aim to investigate the physicochemical and biological properties of Kefiran polysaccharide extracted from Portuguese kefir grains. The kefir growth rate was about 56% (w/w) at room temperature and the kefir pH after 24 h was about 4.6. The obtained yield of Kefiran polysaccharide extracted from the kefir grains was about 4.26% (w/w). The Kefiran structural features were showed in the 1H nuclear magnetic resonance spectrum. The bands observed in the infrared spectrum confirmed that the Kefiran had a β-configuration; and the X-ray photoelectron spectroscopy analysis confirmed the structure and composition of Kefiran and revealed a C/O atomic ratio of 1.46. Moreover, Kefiran showed an average molecular weight (Mw) of 534 kDa and a number-average molecular weight (Mn) of 357 kDa. Regarding the rheological data obtained, Kefiran showed an interesting adhesive performance accompanied by a pseudoplastic behavior, and the extrusion force of Kefiran was 1 N. Furthermore, Kefiran exhibited a higher resistance to hyaluronidase degradation than hyaluronic acid. Finally, Kefiran showed a lack of cytotoxic response through its ability to support metabolic activity and proliferation of L929 cells, and had no effect on these cells’ morphology. Our research suggested that Kefiran polymer has attractive and interesting properties for a wide range of biomedical applications, such as tissue engineering and regenerative medicine.

scholarly journals Germacrone: Occurrence, Synthesis, Chemical Transformations and Biological Properties

2008 ◽  
Vol 3 (4) ◽  
pp. 1934578X0800300 ◽  
Author(s):  
Alejandro F. Barrero ◽  
M. Mar Herrador ◽  
Pilar Arteaga ◽  
Julieta V. Catalán
Keyword(s):  
Essential Oils ◽  
Chemical Reactivity ◽  
Biological Activities ◽  
Biological Properties ◽  
Chemical Transformations ◽  
Cyclization Reactions ◽  
Cns Depressant ◽  
Complete Synthesis ◽  
Wide Range ◽  
Total Oil

Germacrone (1) forms part of a great number of essential oils, in some of them comprising more than 20% of the total oil. This compound presents a wide range of biological activities (CNS depressant, antiinflammatory, antiulcer, antifeedant, antibacterial, antifungal, antitumor, antitussive, vasodilator, choleretic, hepatoprotector), which are analyzed. The chemical reactivity of germacrone, including cyclization reactions, and complete synthesis are presented.

scholarly journals Dendropanax Morbiferus and Other Species from the Genus Dendropanax: Therapeutic Potential of Its Traditional Uses, Phytochemistry, and Pharmacology

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 962
Author(s):  
Rengasamy Balakrishnan ◽  
Duk-Yeon Cho ◽  
In Su-Kim ◽  
Dong-Kug Choi
Keyword(s):  
Therapeutic Potential ◽  
Biological Activities ◽  
Safety Evaluation ◽  
Biological Properties ◽  
Comprehensive Analysis ◽  
Flowering Plant ◽  
High Concentration ◽  
Medicinal Uses ◽  
Wide Range ◽  
Bioactive Ingredients

The Dendropanax genus is a kind of flowering plant in the family of Araliaceae that encompasses approximately 91 to 95 species. Several Dendropanax species are used as traditional medicinal plants, extensively used Korea and South America and other parts of the world. Almost every part of the plant, including the leaves, bark, roots, and stems, can be used as traditional medicine for the prevention and management of a broad spectrum of health disorders. This paper sought to summarizes the ethnopharmacological benefits, biological activities, and phytochemical investigations of plants from the genus Dendropanax, and perhaps to subsequently elucidate potential new perspectives for future pharmacological research to consider. Modern scientific literature suggests that plants of the Dendropanax genus, together with active compounds isolated from it, possess a wide range of therapeutic and pharmacological applications, including antifungal, anti-complement, antioxidant, antibacterial, insect antifeedant, cytotoxic, anti-inflammatory, neuroprotective, anti-diabetic, anti-cancer, and anti-hypouricemic properties. The botanical descriptions of approximately six to 10 species are provided by different scientific web sources. However, only six species, namely, D. morbiferus, D. gonatopodus, D. dentiger, D. capillaris, D. chevalieri, and D. arboreus, were included in the present investigation to undergo phytochemical evaluation, due to the unavailability of data for the remaining species. Among these plant species, a high concentration of variable bioactive ingredients was identified. In particular, D. morbifera is a traditional medicinal plant used for the multiple treatment purposes and management of several human diseases or health conditions. Previous experimental evidence supports that the D. morbifera species could be used to treat various inflammatory disorders, diarrhea, diabetes, cancer, and some microbial infections. It has recently been reported, by our group and other researchers, that D. morbifera possesses a neuroprotective and memory-enhancing agent. A total of 259 compounds have been identified among six species, with 78 sourced from five of these species reported to be bioactive. However, there is no up-to-date information concerning the D. morbifera, its different biological properties, or its prospective benefits in the enhancement of human health. In the present study, we set out to conduct a comprehensive analysis of the botany, traditional medicinal history, and medicinal resources of species of the Dendropanax genus. In addition, we explore several phytochemical constituents identified in different species of the Dendropanax genus and their biological properties. Finally, we offer comprehensive analysis findings of the phytochemistry, medicinal uses, pharmacological actions, and a toxicity and safety evaluation of the D. morbifera species and its main bioactive ingredients for future consideration.

scholarly journals Human α-l-iduronidase. Catalytic properties and an integrated role in the lysosomal degradation of heparan sulphate

1992 ◽  
Vol 282 (3) ◽  
pp. 899-908 ◽  
Author(s):  
C Freeman ◽  
J J Hopwood
Keyword(s):  
Enzyme Activity ◽  
Enzyme Activities ◽  
Human Liver ◽  
Skin Fibroblast ◽  
Catalytic Properties ◽  
Heparan Sulphate ◽  
Structural Features ◽  
Lysosomal Degradation ◽  
Catalytic Activities ◽  
Wide Range

The kinetic parameters (Km and kcat) of human liver alpha-L-iduronidase were determined with a variety of heparin-derived disaccharide and tetrasaccharide substrates. More structurally complex substrates, in which several aspects of the aglycone structure of the natural substrates heparin and heparan sulphate were maintained, were hydrolysed with catalytic efficiencies up to 255 times that observed for the simplest disaccharide substrate to be hydrolysed. The major aglycone structure that influenced both substrate binding and enzyme activity was the presence of a C-6 sulphate ester on the residue adjacent to the iduronic acid residue being hydrolysed. Sulphate ions and a number of substrate and product analogues were potent inhibitors of enzyme activity. Human liver alpha-L-iduronidase activity towards 4-methylumbelliferyl alpha-L-iduronide at pH 4.8 had two Km values of 37 microM and 1.92 mM with corresponding kcat. values of 299 and 650 mol of product formed/min per mol of enzyme respectively, which may explain the wide range of Km values previously reported for alpha-L-iduronidase activity toward its substrate. Skin fibroblast alpha-L-iduronidase activity towards the heparin-derived oligosaccharides was influenced by the same substrate aglycone structural features as was observed for the human liver enzyme. A comparison was made of the effect of substrate aglycone structure upon catalytic activities of the enzymes which act to degrade the highly sulphated regions of heparan sulphate. A model was proposed whereby the substrate is directed from alpha-L-iduronidase to subsequent enzyme activities to ensure the efficient degradation of heparan sulphate.

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