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Methods in Molecular Biology (Clifton,... 2022Glycosaminoglycan (GAG) fine structures from the same animal cells and tissues are controlled not only by the biosynthetic and metabolic enzymes but also by other...
Glycosaminoglycan (GAG) fine structures from the same animal cells and tissues are controlled not only by the biosynthetic and metabolic enzymes but also by other environmental factors, such as chemicals, growth factors, nutritional factors, and isolation procedures. To facilitate direct quantitative comparison of disaccharide compositions from different GAG preparations, several stable isotope labeling strategies have been developed. In this report, 1-phenyl-3-methyl-5-pyrazolone (PMP) and deuterated d5-PMP are used for differential disaccharide labeling and profiling of chondroitin sulfate GAG by high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS).
Topics: Animals; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Disaccharides; Glycosaminoglycans; Mass Spectrometry; Polysaccharides
PubMed: 34626374
DOI: 10.1007/978-1-0716-1398-6_10 -
Angewandte Chemie (International Ed. in... Dec 2019The complex sulfation motifs of heparan sulfate glycosaminoglycans (HS GAGs) play critical roles in many important biological processes. However, an understanding of... (Review)
Review
The complex sulfation motifs of heparan sulfate glycosaminoglycans (HS GAGs) play critical roles in many important biological processes. However, an understanding of their specific functions has been hampered by an inability to synthesize large numbers of diverse, yet defined, HS structures. Herein, we describe a new approach to access the four core disaccharides required for HS/heparin oligosaccharide assembly from natural polysaccharides. The use of disaccharides rather than monosaccharides as minimal precursors greatly accelerates the synthesis of HS GAGs, providing key disaccharide and tetrasaccharide intermediates in about half the number of steps compared to traditional strategies. Rapid access to such versatile intermediates will enable the generation of comprehensive libraries of sulfated oligosaccharides for unlocking the "sulfation code" and understanding the roles of specific GAG structures in physiology and disease.
Topics: Disaccharides; Heparitin Sulfate; Humans; Polysaccharides
PubMed: 31553820
DOI: 10.1002/anie.201908805 -
Marine Drugs May 2023The skin is the largest organ of the human body, composed of a diverse range of cell types, non-cellular components, and an extracellular matrix. With aging, molecules...
The skin is the largest organ of the human body, composed of a diverse range of cell types, non-cellular components, and an extracellular matrix. With aging, molecules that are part of the extracellular matrix undergo qualitative and quantitative changes and the effects, such as a loss of skin firmness or wrinkles, can be visible. The changes caused by the aging process do not only affect the surface of the skin, but also extend to skin appendages such as hair follicles. In the present study, the ability of marine-derived saccharides, L-fucose and chondroitin sulphate disaccharide, to support skin and hair health and minimize the effects of intrinsic and extrinsic aging was investigated. The potential of the tested samples to prevent adverse changes in the skin and hair through stimulation of natural processes, cellular proliferation, and production of extracellular matrix components collagen, elastin, or glycosaminoglycans was investigated. The tested compounds, L-fucose and chondroitin sulphate disaccharide, supported skin and hair health, especially in terms of anti-aging effects. The obtained results indicate that both ingredients support and promote the proliferation of dermal fibroblasts and dermal papilla cells, provide cells with a supply of sulphated disaccharide GAG building blocks, increase ECM molecule production (collagen and elastin) by HDFa, and support the growth phase of the hair cycle (anagen).
Topics: Humans; Elastin; Chondroitin Sulfates; Fucose; Cells, Cultured; Skin; Collagen; Fibroblasts; Disaccharides
PubMed: 37367655
DOI: 10.3390/md21060330 -
Applied Microbiology and Biotechnology Oct 2017Difructose anhydride IV (DFA IV) is a cyclic disaccharide consisting of two fructose residues, which is obtained from levan conversion with levan fructotransferase... (Review)
Review
Difructose anhydride IV (DFA IV) is a cyclic disaccharide consisting of two fructose residues, which is obtained from levan conversion with levan fructotransferase (LFTase) and rarely found in nature as a low-calorie sugar substitute. Some beneficial effects of DFA IV connected with its consumption have been described. The article reviews the properties and physiological functions of DFA IV, levan conversion, resources and properties of LFTase and the produced methods of DFA IV. LFTase as a relatively novel enzyme and its molecular evolution are discussed as well. The aim is to better understand a novel sugar-substituting sweetener of DFA IV as a food additive.
Topics: Biotechnology; Biotransformation; Disaccharides; Fructans; Hexosyltransferases; Sweetening Agents
PubMed: 28905094
DOI: 10.1007/s00253-017-8500-5 -
Scientific Reports Apr 2019Carrageenans are sulfated galactans found in certain red seaweeds with proven biological activities. In this work, we have prepared purified native and degraded κ-,...
Carrageenans are sulfated galactans found in certain red seaweeds with proven biological activities. In this work, we have prepared purified native and degraded κ-, ι-; and λ-carrageenans, including the disaccharides (carrabioses) and disaccharide-alditols (carrabiitols) from seaweed extracts as potential antitumor compounds and identified the active principle of the cytotoxic and potential antitumor properties of these compounds. Both κ and ι-carrageenan, as well as carrageenan oligosaccharides showed cytotoxic effect over LM2 tumor cells. Characterized disaccharides (carrabioses) and the reduced product carrabiitols, were also tested. Only carrabioses were cytotoxic, and among them, κ-carrabiose was the most effective, showing high cytotoxic properties, killing the cells through an apoptotic pathway. In addition, the cells surviving treatment with κ-carrabiose, showed a decreased metastatic ability in vitro, together with a decreased cell-cell and cell-matrix interactions, thus suggesting possible antitumor potential. Overall, our results indicate that most cytotoxic compounds derived from carrageenans have lower molecular weights and sulfate content. Potential applications of the results emerging from the present work include the use of disaccharide units such as carrabioses coupled to antineoplasics in order to improve its cytotoxicity and antimetastatic properties, and the use of ι-carrageenan as adjuvant or carrier in anticancer treatments.
Topics: Animals; Antineoplastic Agents; Biological Products; Carrageenan; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Survival; Disaccharides; Mice; Molecular Structure
PubMed: 31040376
DOI: 10.1038/s41598-019-43238-y -
Journal of Molecular Medicine (Berlin,... Aug 2022Mucopolysaccharidosis type II (MPS II) is a neurometabolic disorder, due to the deficit of the lysosomal hydrolase iduronate 2-sulfatase (IDS). This leads to a severe...
Mucopolysaccharidosis type II (MPS II) is a neurometabolic disorder, due to the deficit of the lysosomal hydrolase iduronate 2-sulfatase (IDS). This leads to a severe clinical condition caused by a multi-organ accumulation of the glycosaminoglycans (GAGs/GAG) heparan- and dermatan-sulfate, whose elevated levels can be detected in body fluids. Since 2006, enzyme replacement therapy (ERT) has been clinically applied, showing efficacy in some peripheral districts. In addition to clinical monitoring, GAG dosage has been commonly used to evaluate ERT efficacy. However, a strict long-term monitoring of GAG content and composition in body fluids has been rarely performed. Here, we report the characterization of plasma and urine GAGs in Ids knock-out (Ids-ko) compared to wild-type (WT) mice, and their changes along a 24-week follow-up, with and without ERT. The concentration of heparan-sulfate (HS), chondroitin-sulfate (CS), and dermatan-sulfate (DS), and of the non-sulfated hyaluronic acid (HA), together with their differentially sulfated species, was quantified by capillary electrophoresis with laser-induced fluorescence. In untreated Ids-ko mice, HS and CS + DS were noticeably increased at all time points, while during ERT follow-up, a substantial decrease was evidenced for HS and, to a minor extent, for CS + DS. Moreover, several structural parameters were altered in untreated ko mice and reduced after ERT, however without reaching physiological values. Among these, disaccharide B and HS 2s disaccharide showed to be the most interesting candidates as biomarkers for MPS II. GAG chemical signature here defined provides potential biomarkers useful for an early diagnosis of MPS II, a more accurate follow-up of ERT, and efficacy evaluations of newly proposed therapies. KEY MESSAGES : Plasmatic and urinary GAGs are useful markers for MPS II early diagnosis and prognosis. CE-LIF allows GAG structural analysis and the quantification of 17 different disaccharides. Most GAG species increase and many structural features are altered in MPS II mouse model. GAG alterations tend to restore to wild-type levels following ERT administration. CS+DS/HS ratio, % 2,4dis CS+DS, and % HS 2s are potential markers for MPS II pathology and ERT efficacy.
Topics: Animals; Biomarkers; Body Fluids; Dermatan Sulfate; Disaccharides; Disease Models, Animal; Enzyme Replacement Therapy; Glycosaminoglycans; Heparitin Sulfate; Mice; Mice, Knockout; Mucopolysaccharidosis II
PubMed: 35816218
DOI: 10.1007/s00109-022-02221-3 -
Carbohydrate Research Dec 2020The indium-mediated allylation followed by ozonolysis has been applied for the elongation of different disaccharides such as cellobiose, lactose and maltose. This...
The indium-mediated allylation followed by ozonolysis has been applied for the elongation of different disaccharides such as cellobiose, lactose and maltose. This reaction sequence and per-O-acetylation produced the expected mixture of α/β-pyranoid as well as α/β-furanoid isomers. The main product in all cases adopted the β-pyranose form and could be isolated and fully characterized with the help of NMR-spin simulations. Thorough investigation of the side products throughout optimization of the conditions for the ozonolysis resulted in the discovery of a novel 12 membered bridged disaccharide.
Topics: Alkenes; Catalysis; Disaccharides; Indium; Isomerism; Ozone
PubMed: 33068775
DOI: 10.1016/j.carres.2020.108170 -
Organic & Biomolecular Chemistry Mar 2023Synthetic deoxy-fluoro-carbohydrate derivatives and seleno-sugars are useful tools in protein-carbohydrate interaction studies using nuclear magnetic resonance...
Synthetic deoxy-fluoro-carbohydrate derivatives and seleno-sugars are useful tools in protein-carbohydrate interaction studies using nuclear magnetic resonance spectroscopy because of the presence of the F and Se reporter nuclei. Seven saccharides containing both these atoms have been synthesized, three monosaccharides, methyl 6-deoxy-6-fluoro-1-seleno-β-D-galactopyranoside (1) and methyl 2-deoxy-2-fluoro-1-seleno-α/β-D-galactopyranoside (2α and 2β), and four disaccharides, methyl 4--(β-D-galactopyranosyl)-2-deoxy-2-fluoro-1-seleno-β-D-glucopyranoside (3), methyl 4-Se-(β-D-galactopyranosyl)-2-deoxy-2-fluoro-4-seleno-β-D-glucopyranoside (4), and methyl 4-Se-(2-deoxy-2-fluoro-α/β-D-galactopyranosyl)-4-seleno-β-D-glucopyranoside (5α and 5β), the three latter compounds with an interglycosidic selenium atom. Selenoglycosides 1 and 3 were obtained from the corresponding bromo sugar by treatment with dimethyl selenide and a reducing agent, while compounds 2α/2β, 4, and 5α/5β were synthesized by the coupling of a D-galactosyl selenolate, obtained from the corresponding isoselenouronium salt, with either methyl iodide or a 4--trifluoromethanesulfonyl D-galactosyl moiety. While benzyl ether protecting groups were found to be incompatible with the selenide linkage during deprotection, a change to acetyl esters afforded 4 in a 17% overall yield and over 9 steps from peracetylated D-galactosyl bromide. The synthesis of 5 was performed similarly, but the 2-fluoro substituent led to reduced stereoselectivity in the formation of the isoselenouronium salt (α/β ∼ 1 : 2.3). However, the β-anomer of the uronium salt could be obtained almost pure (∼98%) by precipitation from the reaction mixture. The following displacement reaction occurred without anomerisation, affording, after deacetylation, pure 5β.
Topics: Lactose; Galactose; Disaccharides; Carbohydrate Conformation
PubMed: 36877217
DOI: 10.1039/d2ob02299k -
Critical Reviews in Analytical Chemistry May 2018Disaccharides are determined mainly for dietetic purposes, hence the most analyses are carried out for food and drink samples. Its content can also be used to profile... (Review)
Review
Disaccharides are determined mainly for dietetic purposes, hence the most analyses are carried out for food and drink samples. Its content can also be used to profile groceries in order to identify the origin and quality of the products. They also can be an indicator of the rate of metabolism as well as for the control of some technological and biotechnological processes. Unfortunately most of technological analysis are performed with nonselective polarimetry methods. Sugars due to specific physicochemical properties of compounds are difficult to determine with classical analytical techniques. The most common disaccharides are composed of several types of monomers connected by a different configuration of the glycosidic bond, therefore, there are subject of the same characteristic reactions. This often enforces the need for pre-separation of sample components. Therefore, nowadays the most popular analytical methodologies for disaccharides determination are based on chromatographic and electrophoretic techniques. An alternative is enzymes application that allow both selective recognition of target analyte and its conversion to easy detected product, allowing detection by relatively simple conventional analytical methods. Another approach is the use of advanced chemometric methodologies for computing of data obtained from some spectroscopic techniques. This article is a review of the recent analytical literature devoted to non-selective and selective methods for disaccharide determination in real samples.
Topics: Chromatography; Disaccharides; Electrophoresis
PubMed: 29053338
DOI: 10.1080/10408347.2017.1391683 -
Safety of intravenous iron isomaltoside for iron deficiency and iron deficiency anemia in pregnancy.Archives of Gynecology and Obstetrics May 2020To evaluate the efficacy and safety for mother and child of using intravenous iron isomaltoside (IV-IIM) during pregnancy. (Review)
Review
PURPOSE
To evaluate the efficacy and safety for mother and child of using intravenous iron isomaltoside (IV-IIM) during pregnancy.
METHODS
Using an appointment register, we retrospectively identified all pregnant women who received a single dose of 1000 or 1500 mg IV-IIM in the maternity ward of Falu Hospital and subsequently gave birth between August 6, 2013 and July 31, 2018. Women who received IV-IIM (case group) were individually matched with pregnant women who did not receive IV-IIM (control group) by delivery date, maternal age (± 2 years), and parity. Adverse drug reactions (ADRs), demographic characteristics, hemoglobin and s-ferritin counts, pregnancy and delivery complications, and infant data (APGAR score, pH at umbilical artery, birthweight, birth length, intrauterine growth restriction and neonatal ward admission). Data were obtained from electronic patient charts. SPSS was used for descriptive statistics.
RESULTS
During the 5-year period, 213 women each received a single administration of IV-IIM. Ten (4.7%) ADRs occurred during IV-IIM administration. All ADRs were mild hypersensitivity reactions, abated spontaneously within a few minutes, and did not recur on rechallenge. No association between IIM dose and ADR frequency was noted. Maternal and fetal outcomes, including hemoglobin counts at delivery and postpartum, were similar in the case and control groups.
CONCLUSION
These results support the convenience, safety, and efficacy of a single high-dose (up to 1500 mg) infusion of IV-IIM for iron deficiency or iron deficiency anemia during pregnancy.
Topics: Administration, Intravenous; Adult; Anemia, Iron-Deficiency; Disaccharides; Female; Ferric Compounds; Humans; Pregnancy; Pregnant Women; Prenatal Care; Retrospective Studies
PubMed: 32270330
DOI: 10.1007/s00404-020-05509-2