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Applied Microbiology and Biotechnology Nov 2019In the daily diet, sweeteners play an indispensable role. Among them, sucrose, a widely occurring disaccharide in nature, is a commonly used sweetener. However, the... (Review)
Review
In the daily diet, sweeteners play an indispensable role. Among them, sucrose, a widely occurring disaccharide in nature, is a commonly used sweetener. However, the intake of sucrose can cause a rapid increase in blood glucose, which leads to a number of health problems. Therefore, there is an urgent need for possible alternatives to sucrose. Currently, four naturally occurring sucrose isomers, trehalulose, turanose, leucrose, and isomaltulose are considered to be possible alternatives to sucrose due to their suitable sweetness, potential physiological benefits, and feasible production processes. This review covers the properties of these alternative sweeteners, including their structure, sweetness, hydrolysis rate, toxicology, and cariogenicity, and exhibits their potential applications in chronic diseases management, anti-inflammatory supplement, prebiotic dietary supplement, and stabilizing agent. The biosynthesis of these sucrose isomers using carbohydrate-active enzymes and their industrial production processes are also systematically summarized.
Topics: Diet; Disaccharides; Food; Humans; Isomaltose; Isomerism; Sucrose; Sweetening Agents; Taste
PubMed: 31587089
DOI: 10.1007/s00253-019-10132-6 -
Analytica Chimica Acta Oct 2023Carbohydrates play crucial regulatory roles in various physiological and pathological processes. However, the low ionization efficiency and the presence of linkage...
Carbohydrates play crucial regulatory roles in various physiological and pathological processes. However, the low ionization efficiency and the presence of linkage pattern, monosaccharide composition and anomeric configuration isomers make their in-depth analysis very challenging, especially for heterogeneous biological tissues. In this study, we propose a high-sensitive and isomer-specific imaging approach to visualize the spatial distributions of monosaccharide and disaccharide isomers by integrating chemical derivatization and matrix-assisted laser desorption/ionization tandem mass spectrometry imaging (MALDI-MSI). 2-Pyridinecarbohydrazide (PYD) is developed as a novel derivatization reagent which can not only improves the MS sensitivity of carbohydrates, but also enables the identification and visualization of ketose and aldose monosaccharide isomers, as well as linkage pattern, monosaccharide composition and anomeric configuration disaccharide isomers by mass spectrometry imaging of isomer-specific MS/MS fragment ions. Moreover, we build quantitative MALDI-MS and MALDI-MSI methods for disaccharide isomers based on the diagnostic fragment ions, and good linear relationships could be achieved both in solution and on glass slides. We expect that this study should provide new ideas for in-depth profiling of the spatial signatures of carbohydrates in biological tissues and lay the foundation for a deeper understanding of carbohydrates' structure.
Topics: Tandem Mass Spectrometry; Monosaccharides; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Disaccharides; Aldehydes
PubMed: 37709472
DOI: 10.1016/j.aca.2023.341741 -
Journal of Medicinal Chemistry Dec 2023In recent years, trehalose, a natural disaccharide, has attracted growing attention because of the discovery of its potential to induce autophagy. Trehalose has also... (Review)
Review
In recent years, trehalose, a natural disaccharide, has attracted growing attention because of the discovery of its potential to induce autophagy. Trehalose has also been demonstrated to preserve the protein's structural integrity and to limit the aggregation of pathologically misfolded proteins. Both of these properties have made trehalose a promising therapeutic candidate to target autophagy-related disorders and protein aggregation diseases. Unfortunately, trehalose has poor bioavailability due to its hydrophilic nature and susceptibility to enzymatic degradation. Recently, trehalose-bearing carriers, in which trehalose is incorporated either by chemical conjugation or physical entrapment, have emerged as an alternative option to free trehalose to improve its efficacy, particularly for the treatment of neurodegenerative diseases, atherosclerosis, nonalcoholic fatty liver disease (NAFLD), and cancers. In the current Perspective, we discuss all existing literature in this emerging field and try to identify key challenges for researchers intending to develop trehalose-bearing carriers to stimulate autophagy or inhibit protein aggregation.
Topics: Humans; Trehalose; Protein Aggregates; Disaccharides; Autophagy; Neurodegenerative Diseases
PubMed: 38031413
DOI: 10.1021/acs.jmedchem.3c01442 -
Applied Microbiology and Biotechnology Apr 2018Difructose dianhydride III (DFA III) is a cyclic difructose containing two reciprocal glycosidic linkages. It is easily generated with a small amount by sucrose... (Review)
Review
Difructose dianhydride III (DFA III) is a cyclic difructose containing two reciprocal glycosidic linkages. It is easily generated with a small amount by sucrose caramelization and thus occurs in a wide range of food-stuffs during food processing. DFA III has half sweetness but only 1/15 energy of sucrose, showing potential industrial application as low-calorie sucrose substitute. In addition, it displays many benefits including prebiotic effect, low cariogenicity property, and hypocholesterolemic effect, and improves absorption of minerals, flavonoids, and immunoglobulin G. DFA III is biologically produced from inulin by inulin fructotransferase (IFTase, EC 4.2.2.18). Plenty of DFA III-producing enzymes have been identified. The crystal structure of inulin fructotransferase has been determined, and its molecular modification has been performed to improve the catalytic activity and structural stability. Large-scale production of DFA III has been studied by various IFTases, especially using an ultrafiltration membrane bioreactor. In this article, the recent findings on physiological effects of DFA III are briefly summarized; the research progresses on identification, expression, and molecular modification of IFTase and large-scale biological production of DFA III by IFTase are reviewed in detail.
Topics: Bioreactors; Biotechnology; Disaccharides; Hexosyltransferases; Inulin; Sweetening Agents
PubMed: 29476401
DOI: 10.1007/s00253-018-8834-7 -
Se Pu = Chinese Journal of... Feb 2023Heparin (Hp) is the most widely used anticoagulant drug in the clinics, with an annual global output of over 10 billion dollars. Hp, a member of the... (Review)
Review
Heparin (Hp) is the most widely used anticoagulant drug in the clinics, with an annual global output of over 10 billion dollars. Hp, a member of the glycosaminoglycans (GAGs), is prepared from porcine intestinal mucosa via extraction, separation, and purification. Hp is a linear polysaccharide with repeating disaccharide units. Low-molecular-weight heparins (LMWHs) are depolymerized from Hp via chemical or enzymatic degradation. Compared with Hp, LMWHs exhibit less bleeding side effect, milder immunogenicity, and higher bioavailability when injected subcutaneously. In general, Hps, including LMWHs, are high complex drugs with large molecular weights (MWs), inhomogeneous MW distributions, and structural heterogeneity, including different degrees and locations of sulfonation, and unique residues generated from different production processes. Thus, developing efficient analytical methods to elucidate the structures of Hps and characterize or quantitate their properties is extremely challenging. Unfortunately, this problem limits their quality control, production optimization, clinical safety monitoring, and new applications. Research has constantly sought to elucidate the complicated structures of Hp drugs. Among the structural analysis and quality control methods of Hp currently available, chromatographic methods are the most widely studied and used. However, no literature thoroughly summarizes the specific applications of chromatographic methods in the structural analysis, manufacturing process, and quality control of Hp drugs. This paper systematically organizes and describes recent research progresses of the chromatographic methods used to analyze Hp drugs, including the identification and composition of monosaccharides, disaccharides, oligosaccharides, and polysaccharides. The applications, innovations, and limitations of these chromatographic methods are also summarized in this review. The insights obtained in this study will help production and quality control personnel, as well as drug researchers, obtain a deeper understanding of the complex structures of Hp drugs. This paper also provides a comprehensive reference for the structural analysis and quality control of Hps, proposes ideas for the development of new quality control methods, and lays a strong foundation for the in-depth structural elucidation of Hp drugs.
Topics: Animals; Swine; Heparin; Heparin, Low-Molecular-Weight; Anticoagulants; Chromatography; Heparin Lyase; Disaccharides
PubMed: 36725707
DOI: 10.3724/SP.J.1123.2022.07020 -
Cellular Immunology Nov 2018Glycosylation is profoundly involved in various diseases, and interactions between glycan binding proteins and their sugar ligands are plausible drug targets. Keratan... (Review)
Review
Glycosylation is profoundly involved in various diseases, and interactions between glycan binding proteins and their sugar ligands are plausible drug targets. Keratan sulfate (KS), a glycosaminoglycan, is downregulated in lungs by cigarette smoking, suggesting that KS is involved in smoking-related diseases, such as chronic obstructive pulmonary disease (COPD). We found that a highly sulfated KS disaccharide, L4, suppresses lung inflammation and is effective against COPD and its exacerbation in mouse models. Its anti-inflammatory activity was comparable to that of a steroid. As a possible mechanism, langerin, a C-type lectin receptor (CLR) expressed in dendritic cells, was suggested to function as an L4 receptor. Oligomeric L4 derivatives were chemically designed to create new ligands with higher affinity and activity. The synthetic L4 oligomers bound to langerin with over 1000-fold higher affinity than the L4 monomer, suggesting that these compounds are effective drug candidates against COPD and inflammatory diseases.
Topics: Animals; Dendritic Cells; Disaccharides; Emphysema; Humans; Keratan Sulfate; Lectins, C-Type; Pulmonary Disease, Chronic Obstructive
PubMed: 30025865
DOI: 10.1016/j.cellimm.2018.07.004 -
Biomedicine & Pharmacotherapy =... Jun 2022Plant-based phytochemicals are now being used to treat plenty of physiological diseases. Herbal drugs have gained popularity in recent years because of their strength,... (Review)
Review
Plant-based phytochemicals are now being used to treat plenty of physiological diseases. Herbal drugs have gained popularity in recent years because of their strength, purity, and cheap cost-effectiveness. Citrus fruits contain significant amounts of flavanones, which falls to the category of polyphenols. Flavanones occupy a major fraction of the total polyphenols present in the plasma when orange juice is taken highly or in moderate states. Narirutin is a disaccharide derivative available in citrus fruits, primarily dihydroxy flavanone. From a pharmacological viewpoint, narirutin is a bioactive phytochemical with therapeutic efficacy. Many experimental researches were published on the use of narirutin. Anticancer activity, neuroprotection, stress relief, hepatoprotection, anti-allergic activity, antidiabetic activity, anti-adipogenic activity, anti-obesity action, and immunomodulation are a couple of the primary pharmacological properties. Narirutin also has antioxidant, and anti-inflammatory activities. The ultimate goal of this review is to provide the current scenario of pharmacological research with narirutin; to make a better understanding for therapeutic potential of narirutin, as well as its biosynthesis strategies and side effects. Extensive literature searches and studies were undertaken to determine the pharmacological properties of narirutin.
Topics: Citrus; Disaccharides; Flavanones; Flavonoids; Polyphenols; Prospective Studies
PubMed: 35413599
DOI: 10.1016/j.biopha.2022.112932 -
Carbohydrate Polymers Apr 2022Commercial porcine intestinal mucosal heparan sulfate (HS) is a valuable material for research into its biological functions. As it is usually produced as a side-stream...
Commercial porcine intestinal mucosal heparan sulfate (HS) is a valuable material for research into its biological functions. As it is usually produced as a side-stream of pharmaceutical heparin manufacture, its chemical composition may vary from batch to batch. We analysed the composition and structure of nine batches of HS from the same manufacturer. Statistical analysis of the disaccharide compositions placed these batches in three categories: group A had high GlcNAc and GlcNS, and low GlcN typical of HS; group B had high GlcN and GlcNS, and low GlcNAc; group C had high di- and trisulfated, and low unsulfated and monosulfated disaccharide repeats. These batches could be placed in the same categories based on their H NMR spectra and molecular weights. Anticoagulant and growth factor binding activities of these HS batches did not fit within these same groups but were related to the proportions of more highly sulfated disaccharide repeats.
Topics: Animals; Anticoagulants; Disaccharides; Factor Xa; Heparitin Sulfate; Intercellular Signaling Peptides and Proteins; Intestinal Mucosa; Swine
PubMed: 35123736
DOI: 10.1016/j.carbpol.2021.119081 -
Nature Aug 2022The identification of general and efficient methods for the construction of oligosaccharides stands as one of the great challenges for the field of synthetic chemistry....
The identification of general and efficient methods for the construction of oligosaccharides stands as one of the great challenges for the field of synthetic chemistry. Selective glycosylation of unprotected sugars and other polyhydroxylated nucleophiles is a particularly significant goal, requiring not only control over the stereochemistry of the forming bond but also differentiation between similarly reactive nucleophilic sites in stereochemically complex contexts. Chemists have generally relied on multi-step protecting-group strategies to achieve site control in glycosylations, but practical inefficiencies arise directly from the application of such approaches. Here we describe a strategy for small-molecule-catalyst-controlled, highly stereo- and site-selective glycosylations of unprotected or minimally protected mono- and disaccharides using precisely designed bis-thiourea small-molecule catalysts. Stereo- and site-selective galactosylations and mannosylations of a wide assortment of polyfunctional nucleophiles is thereby achieved. Kinetic and computational studies provide evidence that site-selectivity arises from stabilizing C-H/π interactions between the catalyst and the nucleophile, analogous to those documented in sugar-binding proteins. This work demonstrates that highly selective glycosylation reactions can be achieved through control of stabilizing non-covalent interactions, a potentially general strategy for selective functionalization of carbohydrates.
Topics: Catalysis; Chemistry Techniques, Synthetic; Disaccharides; Glycosylation; Kinetics; Monosaccharides; Stereoisomerism; Sugars
PubMed: 35709829
DOI: 10.1038/s41586-022-04958-w -
Chembiochem : a European Journal of... Jun 2017Fifty-five mono- and disaccharide analogues were prepared and used for the construction of microarrays to uncover lectin-selective ligands. The microarray study showed...
Fifty-five mono- and disaccharide analogues were prepared and used for the construction of microarrays to uncover lectin-selective ligands. The microarray study showed that two disaccharide analogues, 28' and 44', selectively bind to Solanum tuberosum lectin (STL) and wheat germ agglutinin (WGA), respectively. Cell studies indicated that 28' and 44' selectively block the binding of STL and WGA to mammalian cells, unlike the natural ligand LacNAc, which suppresses binding of both STL and WGA to cells.
Topics: Carbocyanines; Carbohydrate Conformation; Disaccharides; Dose-Response Relationship, Drug; Fluorescent Dyes; HeLa Cells; Humans; Ligands; Microarray Analysis; Monosaccharides; Plant Lectins; Protein Binding; Solanum tuberosum; Staining and Labeling; Triticum; Wheat Germ Agglutinins
PubMed: 28422419
DOI: 10.1002/cbic.201700091