-
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 -
Analytica Chimica Acta May 2022Glycans are ubiquitous, structurally diverse molecules that have specific and general roles involving metabolism, structure, and cell-to-cell signaling. Functional...
Glycans are ubiquitous, structurally diverse molecules that have specific and general roles involving metabolism, structure, and cell-to-cell signaling. Functional specificity depends strongly on the complexity of structures that polysaccharides can adopt based on their subunit composition, length, extent of branching, glycosidic bond connectivity and anomeric configuration. However, a rapid and comprehensive characterization of glycan isomers can be challenging owing to limitations associated with their separation. Here, ten composition, anomeric and connectivity disaccharide isomers were separated and detected using high-resolution differential ion mobility-mass spectrometry (DMS-MS, also known as FAIMS). Focus was primarily directed to compositional isomers corresponding to epimers that differ by the axial or equatorial position of a single hydroxyl group. DMS resolving power was enhanced 14-fold primarily by increasing the fraction of helium in the ion carrier gas and lowering the flow rate. At relatively high disaccharide concentrations, DMS-MS of each disaccharide resulted in complex and unique multi-peak spectra with up to ten fully and partially resolved peaks for β-1,4-mannobiose (Man-1,4β-Man), which can be attributed to the DMS separation and subsequent dissociation of ionic non-covalently bound oligomers into monomer ions. Each DMS spectrum has at least one differentiating peak that is not in the other spectra, indicating that DMS can be used to fully or partially resolve composition, configuration and connectivity isomers. At relatively low disaccharide concentrations, mixtures of disaccharide epimers can also be readily separated by DMS. The integration of high-resolution, ambient pressure DMS with complementary reduced-pressure ion mobility and MS-based glycomics and glycoproteomics workflows may be useful for improving the characterization of glycans and glycosylated biomolecules.
Topics: Disaccharides; Humans; Ions; Isomerism; Mass Spectrometry
PubMed: 35473855
DOI: 10.1016/j.aca.2022.339783 -
Alimentary Pharmacology & Therapeutics Sep 2019
Topics: Disaccharides; Ferric Compounds; Humans; Hypophosphatemia; Incidence; Inflammatory Bowel Diseases; Iron; Maltose
PubMed: 31414533
DOI: 10.1111/apt.15437 -
Biotechnology Advances Nov 2022Sucrose, one of the most widespread disaccharides in nature, has been available in daily human life for many centuries. As an abundant and cheap sweetener, sucrose plays... (Review)
Review
Sucrose, one of the most widespread disaccharides in nature, has been available in daily human life for many centuries. As an abundant and cheap sweetener, sucrose plays an essential role in our diet and the food industry. However, it has been determined that many diseases, such as obesity, diabetes, hyperlipidemia, etc., directly relate to the overconsumption of sucrose. It arouses many explorations for the conversion of sucrose to high-value chemicals. Production of valuable substances from sucrose by chemical methods has been studied since a half-century ago. Compared to chemical processes, biotechnological conversion approaches of sucrose are more environmentally friendly. Many enzymes can use sucrose as the substrate to generate functional sugars, especially those from GH68, GH70, GH13, and GH32 families. In this review, enzymatic catalysis and whole-cell fermentation of sucrose for the production of valuable chemicals were reviewed. The multienzyme cascade catalysis and metabolic engineering strategies were addressed.
Topics: Biotechnology; Disaccharides; Humans; Sucrose; Sugars; Sweetening Agents
PubMed: 35640819
DOI: 10.1016/j.biotechadv.2022.107990 -
Yakugaku Zasshi : Journal of the... 2021Two novel β-trefoil lectins, MytiLec-1 and SeviL were found from mussels in the coast of Yokohama and Nagasaki. MytiLec-1 was purified from gill and mantle of Mytilus... (Review)
Review
Two novel β-trefoil lectins, MytiLec-1 and SeviL were found from mussels in the coast of Yokohama and Nagasaki. MytiLec-1 was purified from gill and mantle of Mytilus galloprovincialis. It was consisted of 149 amino acid residues and there was no similarity with any other proteins when it was discovered. We advocate for this "Mytilectin" as a new protein family because of their novelty of its primary structure and homologues were also found in other mussels. Glycan array analysis revealed that MytiLec-1 specifically bound to the Gb3 and Gb4 glycan which contained the α-galactoside. MytiLec-1 caused the apoptosis against the Burkitt's lymphoma cells through the interaction of Gb3 express in their cell surface. On the other hand, SeviL obtained from gill and mantle of Mytilisepta virgata showed the specific binding against GM1b, asialo GM1 and SSEA-4 which are known as glycosphingolipid glycan including the β-galactoside. In addition, SeviL was identified as R type lectin by confirmation of QXW motif within its primary structure. Messenger RNA of SeviL like R type lectins was also found among the musssels including Mytilus galloprovincialis. SeviL also showed the apoptosis against asialo GM1 expressing cells. To apply the anticancer lectin as a novel molecular target drug, primary structure of MytiLec-1 was analyzed to enhance the stabilization of confirmation by computational design technique. It was succeeded to produce a monomeric artificial β-trefoil lectin, Mitsuba-1 without losing the Gb3 binding ability. Comparison of biological function between Mitsuba-1 and MytiLec-1 is also described in this study.
Topics: Animals; Antineoplastic Agents; Burkitt Lymphoma; Disaccharides; Drug Design; Galectins; Lectins; Molecular Conformation; Molecular Targeted Therapy; Mytilidae; Polysaccharides; Tandem Repeat Sequences; Trisaccharides
PubMed: 33790114
DOI: 10.1248/yakushi.20-00215 -
Bioproduction and applications of aldobionic acids with a focus on maltobionic and cellobionic acid.Bioprocess and Biosystems Engineering Jul 2023Aldobionic acids are sugar acids which consist of a disaccharide with an anomeric acid group. The most famous is lactobionic acid (LBA). LBA is used in many applications... (Review)
Review
Aldobionic acids are sugar acids which consist of a disaccharide with an anomeric acid group. The most famous is lactobionic acid (LBA). LBA is used in many applications such as food and beverages, pharmaceuticals and medicine, cosmetics or chemical processes. During the last decade, all these industries are observing a shift of consumer preferences towards plant-based options. Thus, the biotechnological industry is trying to replace the animal-derived LBA. Maltobionic acid (MBA) and cellobionic acid (CBA) are two stereoisomers of LBA which have emerged as vegan alternatives. However, MBA and CBA face different obstacles related to their industrial production. While traditionally used electrochemical or chemical catalysis often rely on cost intensive and/or hazardous catalysts, novel production methods with microorganisms are still poorly studied. In the first part, this paper discusses both alternatives in terms of their characteristics and applications. In the second part, it reviews the long-studied chemical production and the novel bioproduction methods, which are based on enzymatic and microbial systems. This review concludes with a discussion of future work needed to bring their production to the industrial scale.
Topics: Animals; Disaccharides; Biotechnology
PubMed: 37058246
DOI: 10.1007/s00449-023-02872-7 -
World Journal of Microbiology &... Oct 2023Bifidobacterium is a major probiotic of intestinal gut flora and exerts many physiological activities, and it is widely applied in the fields of food and medicine. As an... (Review)
Review
Bifidobacterium is a major probiotic of intestinal gut flora and exerts many physiological activities, and it is widely applied in the fields of food and medicine. As an important part of Bifidobacterium, glycoside hydrolase plays a role in its physiological activity. With the continuous development and improvement of genetic engineering technology, research on this type of enzyme will play a crucial role in promoting the further development of Bifidobacterium in the field of probiotics. In this review, the preparation methods, enzymatic properties, and functions of glycoside hydrolase extracted from Bifidobacterium are described and summarized. The common method for preparing glycoside hydrolase derived from Bifidobacterium is heterologous expression in Escherichia coli BL21. The optimal pH range for these glycoside hydrolase enzymes is between 4.5 and 7.5; the optimal temperature is between 30 and 50 °C, which is close to the optimal growth condition of Bifidobacterium. Based on substrate specificity, these glycoside hydrolase could hydrolyze synthetic substrates and natural oligosaccharides, including a series of pNP artificial substrates, disaccharide, and trisaccharides, while they have little ability to hydrolyze polysaccharide substrates. This review will be expected to provide a basis for the development of Bifidobacterium as a probiotic element.
Topics: Bifidobacterium; Glycoside Hydrolases; Disaccharides; Oligosaccharides; Substrate Specificity
PubMed: 37843698
DOI: 10.1007/s11274-023-03770-6 -
Organic & Biomolecular Chemistry Apr 2020S-Glycosides are important tools for the elucidation of specific protein-carbohydrate interactions and can significantly aid structural and functional studies of...
S-Glycosides are important tools for the elucidation of specific protein-carbohydrate interactions and can significantly aid structural and functional studies of carbohydrate-active enzymes, as they are often inert or act as enzyme inhibitors. In this context, this work focuses on the introduction of an S-linkage into arabinoxylan oligosaccharides (AXs) in order to obtain a small collection of synthetic tools for the study of AXs degrading enzymes. The key step for the introduction of the S-glycosidic linkage involved anomeric thiol S-alkylation of an orthogonally protected l-arabinopyranoside triflate. The resulting S-linked disaccharide was subsequently employed in a series of glycosylation reactions to obtain a selectively protected tetrasaccharide. This could be further elaborated through chemoselective deprotection and glycosylation reactions to introduce branching l-arabinofuranosides.
Topics: Arabinose; Cross-Linking Reagents; Disaccharides; Glycosides; Glycosylation; Oligosaccharides; Sulfhydryl Compounds; Xylans
PubMed: 32206767
DOI: 10.1039/d0ob00470g -
Journal of Animal Physiology and Animal... Jul 2022The aim of this study was to determine the effect of an increased mono- and disaccharide (MD) intake on selected functions and structure of the gastrointestinal tract...
The aim of this study was to determine the effect of an increased mono- and disaccharide (MD) intake on selected functions and structure of the gastrointestinal tract (GIT), and selected blood parameters in Reeves's muntjac (Muntiacus reevesi), a small browsing ruminant. Eighteen male muntjacs were fed diets consisting of lucerne (ad libitum), a high fibre pellet (100 g/day) and wheat bran (30 g/day) without (MD0) or with addition of 10 or 20 g of glucose, fructose and sucrose mixture/day (MD10 and MD20, respectively) for 14 days. MD dosages were set to increase intake of these saccharides by 25% and 50% relative to MD0, which resulted in a range of water-soluble carbohydrate content in the consumed dry matter from 7% to 12%. Compared to MD0 animals, MD20 animals had a lower dry matter intake, a higher MD concentrations in the reticulorumen (RR), abomasal and small intestinal digesta, higher ruminal butyrate concentration, higher SGLT1 expression in the epithelium of proximal jejunum, higher plasma glucose, lower RR tissue weight but greater caecal tissue weight (p ≤ 0.05), and had or tended to have shorter papillae and lower mucosa surface area in the Atrium ruminis (by 44%; p = 0.02 and p = 0.10, respectively); MD10 animals tended to have higher MD concentrations in the abomasal and small intestinal digesta (p ≤ 0.10), and a higher amylolytic activity (p = 0.02) as well as a tendency to lower xylanolytic activity in the RR digesta (p = 0.06). MD supplementation did not affect ruminal pH. In conclusion, low to moderate increase of MD intake increased MD concentrations in the RR, abomasal and intestinal digesta, and SGLT1 expression in intestinal epithelium, suggesting incomplete fermentation of those saccharides in the RR. MD supplementation dose-dependently affects structure of GIT in Reeves's muntjac.
Topics: Animal Feed; Animals; Diet; Dietary Fiber; Disaccharides; Fermentation; Gastrointestinal Tract; Male; Muntjacs; Rumen
PubMed: 35587535
DOI: 10.1111/jpn.13727 -
Biomacromolecules Mar 2021Glycosaminoglycans (GAGs) are conserved polysaccharides composed of linear repeating disaccharides and play crucial roles in multiple biological processes in animal...
Glycosaminoglycans (GAGs) are conserved polysaccharides composed of linear repeating disaccharides and play crucial roles in multiple biological processes in animal kingdom. However, saccharide-branched GAGs are rarely found, except the fucose-branched one from sea cucumbers. There was conjecture about the presence of disaccharide-branched GAG since 30 years ago, though not yet confirmed. Here, we report a GAG containing galactose-fucose branches from . This unique branch was confirmed as d-Gal-α1,2-l-Fuc by structural elucidation of oligosaccharides prepared from GAG. Bioassays indicated that oligomers with a larger degree of polymerization exhibited a potent anticoagulation by targeting the intrinsic tenase. Heptasaccharide was proven as the minimum fragment retaining the anticoagulant potential and showed 92.6% inhibition of venous thrombosis in vivo at sc. of 8 mg/kg with no obvious bleeding risks. These results not only solve a long-standing question about the presence of disaccharide-branched GAG in Holothuroidea, but open up new opportunities to develop safer anticoagulants.
Topics: Animals; Anticoagulants; Blood Coagulation; Disaccharides; Glycosaminoglycans; Sea Cucumbers
PubMed: 33616386
DOI: 10.1021/acs.biomac.0c01739