Showing papers on "Disaccharide published in 2019"
TL;DR: In this article, an economical, efficient, and sustainable catalytic process with excellent EcoScore and E-factor values for the selective, two-step synthesis of 2,5-diformylfuran (with a yield higher than 90%) from carbohydrates, especially disaccharide and polysaccharide.
27 citations
TL;DR: By employing a multistage modeling approach in combination with the experimental data, this work can rationalize the conformation on the surface as well as the interactions between the sucrose molecules, thereby yielding models of the observed self‐assembled patterns on thesurface.
Abstract: Saccharides are ubiquitous biomolecules, but little is known about their interaction with, and assembly at, surfaces. By combining preparative mass spectrometry with scanning tunneling microscopy, we have been able to address the conformation and self-assembly of the disaccharide sucrose on a Cu(100) surface with subunit-level imaging. By employing a multistage modeling approach in combination with the experimental data, we can rationalize the conformation on the surface as well as the interactions between the sucrose molecules, thereby yielding models of the observed self-assembled patterns on the surface.
25 citations
TL;DR: A synthetic method for α-CH2-linked disaccharide structures, such as Glc(1,6)-Glc, is described by stereoselective radical-coupling C-glycosylation between a conformationally constrained and stable C1-sp3 hybridized xanthate donor and a carefully designed acceptor.
23 citations
TL;DR: The data showed that there is a need to determine and monitor the anomeric content of lactose and this should be a priority to both the manufacturers and the formulators of medicines.
22 citations
27 Jun 2019
TL;DR: The results show that glucose induces a broadening of the active site tunnel through residues lining the tunnel and facilitates the accumulation of glucose, and the increase in glucose concentrations leads to a decrease in the number of water molecules inside the tunnel to affect substrate hydrolysis.
Abstract: β-Glucosidase (EC 3.2.1.21) plays an essential role in the removal of glycosyl residues from disaccharide cellobiose to produce glucose during the hydrolysis of lignocellulosic biomass. Although there exist a few β-glucosidase that are tolerant to large concentrations of glucose, these enzymes are typically prone to glucose inhibition. Understanding the basis of this inhibition is important for the production of cheaper biofuels from lignocellulose. In this study, all-atom molecular dynamics simulation at different temperatures and glucose concentrations was used to understand the molecular basis of glucose inhibition of GH1 β-glucosidase (B8CYA8) from Halothermothrix orenii. Our results show that glucose induces a broadening of the active site tunnel through residues lining the tunnel and facilitates the accumulation of glucose. In particular, we observed that glucose accumulates at the tunnel entrance and near the catalytic sites to block substrate accessibility and inhibit enzyme activity. The reductio...
18 citations
TL;DR: An improved liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitation of glycosidic linkages derived from disaccharides, oligosaccharide, and polysaccharides present in complicated matrices is presented.
Abstract: The extensive characterization of glycosidic linkages in carbohydrates remains a challenge because of the lack of known standards and limitations in current analytical techniques. This study encompasses the construction of an extensive glycosidic linkage library built from synthesized standards. It includes an improved liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitation of glycosidic linkages derived from disaccharides, oligosaccharides, and polysaccharides present in complicated matrices. We present a method capable of the simultaneous identification of over 90 unique glycosidic linkages using ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC/QqQ MS) operated in dynamic multiple reaction monitoring (dMRM) mode. To build the library, known monosaccharides commonly found in plants were subjected to partial methylation to yield partially derivatized species representing trisecting, bisecting, linear, and terminal structures. The library includes glycosidic linkage information for three hexoses (glucose, galactose, and mannose), three pentoses (xylose, arabinose, and ribose), two deoxyhexoses (fucose and rhamnose), and two hexuronic acids (glucuronic acid and galacturonic acid). The resulting partially methylated monosaccharides were then labeled with 1-phenyl-3-methyl-5-pyrazolone (PMP) followed by separation and analysis by UHPLC/dMRM MS. Validation of the synthesized standards was performed using disaccharide, oligosaccharide, and polysaccharide standards. Accuracy, reproducibility, and robustness of the method was demonstrated by analysis of xyloglucan (tamarind) and whole carrot root. The synthesized standards represent the most comprehensive group of carbohydrate linkages to date.
17 citations
TL;DR: The results suggest that the control of postprandial hyperglycemia may be mediated by the inhibition of disaccharide digestion, such as sucrose and lactose, and the regulation of the absorption of glucose.
Abstract: Twelve terpenoids were evaluated in the treatment of type 2 diabetes mellitus: seven monoterpenes (geranyl acetate (1), geranic acid (2), citral (3), geraniol (4), methyl geranate (5), nerol (6), and citronellic acid (7)), three sesquiterpenes (farnesal (8), farnesol (9), and farnesyl acetate (10)), one diterpene (geranylgeraniol (11)), and one triterpene (squalene (12)) were selected to carry out a study on normoglycemic and streptozotocin-induced diabetic mice. Among these, 2, 3, 7, 8, 9, and 10 showed antihyperglycemic activity in streptozotocin-induced diabetic mice. They were then selected for evaluation in oral sucrose and lactose tolerance tests (OSTT and OLTT) as well as in an oral glucose tolerance test (OGTT). In the OSTT and OLTT, compounds 3, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a sucrose or lactose load (comparable to acarbose). In the case of the OGTT, 2, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a glucose load (comparable to canagliflozin). Our results suggest that the control of postprandial hyperglycemia may be mediated by the inhibition of disaccharide digestion, such as sucrose and lactose, and the regulation of the absorption of glucose. The first case could be associated with an ∝ -glucosidase inhibitory effect and the second with an inhibition of the sodium-glucose type 1 (SGLT-1) cotransporter. Finally, five acyclic terpenes may be candidates for the development and search for new α-glucosidase and SGLT-1 cotransporter inhibitors.
16 citations
TL;DR: The isolation and characterization of a selective β-N-acetylhexosaminidase from the fungal strain of Aspergillus versicolor is presented and the resulting model glycoconjugate is applicable as a selective ligand of galectin-3 — a biomedically attractive human lectin.
Abstract: β-N-Acetylhexosaminidases (EC 3.2.1.52) are typical of their dual activity encompassing both N-acetylglucosamine and N-acetylgalactosamine substrates. Here we present the isolation and characterization of a selective β-N-acetylhexosaminidase from the fungal strain of Aspergillus versicolor. The enzyme was recombinantly expressed in Pichia pastoris KM71H in a high yield and purified in a single step using anion-exchange chromatography. Homologous molecular modeling of this enzyme identified crucial differences in the enzyme active site that may be responsible for its high selectivity for N-acetylglucosamine substrates compared to fungal β-N-acetylhexosaminidases from other sources. The enzyme was used in a sequential reaction together with a mutant β-N-acetylhexosaminidase from Talaromyces flavus with an enhanced synthetic capability, affording a bioactive disaccharide bearing an azido functional group. The azido function enabled an elegant multivalent presentation of this disaccharide on an aromatic carrier. The resulting model glycoconjugate is applicable as a selective ligand of galectin-3 — a biomedically attractive human lectin. These results highlight the importance of a general availability of robust and well-defined carbohydrate-active enzymes with tailored catalytic properties for biotechnological and biomedical applications.
16 citations
TL;DR: It is demonstrated that the enzymatic synthesis of trehalose from glucose and a nucleotide sugar is reversible by approaching the thermodynamic equilibrium in both the synthesis and hydrolysis directions, and uridine establishes an equilibrium constant which is more in favor of the product tre Halose than when adenosine is employed as the nucleotide under identical conditions.
Abstract: LeLoir glycosyltransferases are important biocatalysts for the production of glycosidic bonds in natural products, chiral building blocks, and pharmaceuticals. Trehalose transferase (TreT) is of particular interest since it catalyzes the stereo- and enantioselective α,α-(1→1) coupling of a nucleotide sugar donor and monosaccharide acceptor for the synthesis of disaccharide derivatives. Heterologously expressed thermophilic trehalose transferases were found to be intrinsically aggregation prone and are mainly expressed as catalytically active inclusion bodies in Escherichia coli. To disfavor protein aggregation, the thermostable protein mCherry was explored as a fluorescent protein tag. The fusion of mCherry to trehalose transferase from Pyrobaculum yellowstonensis (PyTreT) demonstrated increased protein solubility. Chaotropic agents like guanidine or the divalent cations Mn(II), Ca(II), and Mg(II) enhanced the enzyme activity of the fusion protein. The thermodynamic equilibrium constant, Keq, for the reversible synthesis of trehalose from glucose and a nucleotide sugar was determined in both the synthesis and hydrolysis directions utilizing UDP-glucose and ADP-glucose, respectively. UDP-glucose was shown to achieve higher conversions than ADP-glucose, highlighting the importance of the choice of nucleotide sugars for LeLoir glycosyltransferases under thermodynamic control. IMPORTANCE The heterologous expression of proteins in Escherichia coli is of great relevance for their functional and structural characterization and applications. However, the formation of insoluble inclusion bodies is observed in approximately 70% of all cases, and the subsequent effects can range from reduced soluble protein yields to a complete failure of the expression system. Here, we present an efficient methodology for the production and analysis of a thermostable, aggregation-prone trehalose transferase (TreT) from Pyrobaculum yellowstonensis via its fusion with mCherry as a thermostable fluorescent protein tag. This fusion strategy allowed for increased enzyme stability and solubility and could be applied to other (thermostable) proteins, allowing rapid visualization and quantification of the mCherry-fused protein of interest. Finally, we have demonstrated that the enzymatic synthesis of trehalose from glucose and a nucleotide sugar is reversible by approaching the thermodynamic equilibrium in both the synthesis and hydrolysis directions. Our results show that uridine establishes an equilibrium constant which is more in favor of the product trehalose than when adenosine is employed as the nucleotide under identical conditions. The influence of different nucleotides on the reaction can be generalized for all LeLoir glycosyltransferases under thermodynamic control as the position of the equilibrium depends solely on the reaction conditions and is not affected by the nature of the catalyst.
15 citations
TL;DR: Kinetic modelling was used to investigate the role of maltose in the formation of acrylamide during the finish-frying of french fries, and suggested that under these conditions, it is unlikely that acrieslamide is formed directly from the maltose-asparagine conjugate.
14 citations
TL;DR: Interestingly, the sugar mixture obtained in the biosynthetic reactions also contained oligosaccharides such as esculose, a rare trisaccharide with no previous NMR structure elucidation, as well as erlose, melezitose and theanderose, all of which are naturally found in honey.
Abstract: Metschnikowia reukaufii is a widespread yeast able to grow in the plants' floral nectaries, an environment of extreme conditions with sucrose concentrations exceeding 400 g l-1 , which led us into the search for enzymatic activities involved in this sugar use/transformation. New oligosaccharides were produced by transglucosylation processes employing M. reukaufii cell extracts in overload-sucrose reactions. These products were purified and structurally characterized by MS-ESI and NMR techniques. The reaction mixture included new sugars showing a great variety of glycosidic bonds including α-(1→1), α-(1→3) and α-(1→6) linkages. The main product synthesized was the trisaccharide isomelezitose, whose maximum concentration reached 81 g l-1 , the highest amount reported for any unmodified enzyme or microbial extract. In addition, 51 g l-1 of the disaccharide trehalulose was also produced. Both sugars show potential nutraceutical and prebiotic properties. Interestingly, the sugar mixture obtained in the biosynthetic reactions also contained oligosaccharides such as esculose, a rare trisaccharide with no previous NMR structure elucidation, as well as erlose, melezitose and theanderose. All the sugars produced are naturally found in honey. These compounds are of biotechnological interest due to their potential food, cosmeceutical and pharmaceutical applications.
TL;DR: A fermentation-coupling biocatalysis process involving recombinant bacteria fermentation to secrete TreS and simultaneous conversion of maltose to trehalose by TreS is invented and it is found that this is an efficient strategy for large-scale tre Halose production using recombinant B. subtilis.
Abstract: Trehalose, a stable nonreducing disaccharide, protects biomolecules against environmental stress. However, trehalose production using secretory trehalose synthase (TreS) by Bacillus subtilis has not been well studied. In this study, a mutant TreS was successfully secreted and expressed in B. subtilis WB800N. The extracellular enzyme activity of TreS regulated by the P43 promoter and SPPhoD signal peptide in recombinant B. subtilis WB800N reached 23080.6 ± 1119.4 U/L in a 5-L fermenter after optimizing the culture medium, while xpF, skfA, lytC, and sdpC were knocked out. To reduce maltose consumption, malP and amyE corresponding to maltose transporters were further deleted. To simplify the trehalose production process, we invented a fermentation-coupling biocatalysis process involving recombinant bacteria fermentation to secrete TreS and simultaneous conversion of maltose to trehalose by TreS and found that the conversion rate of maltose to trehalose reached 75.5%, suggesting that this is an efficient strategy for large-scale trehalose production using recombinant B. subtilis.
TL;DR: The X‐ray crystal structures of PsLBP in complex with Glc1P and Man1P have been solved, providing the first molecular detail of the recognition of a noncognate donor substrate by GPs, which revealed the importance of hydrogen bonding between the active site residues and hydroxy groups at C2, C4, and C6 of sugar 1‐phosphates.
Abstract: Glycoside phosphorylases (GPs) carry out a reversible phosphorolysis of carbohydrates into oligosaccharide acceptors and the corresponding sugar 1‐phosphates. The reversibility of the reaction enables the use of GPs as biocatalysts for carbohydrate synthesis. Glycosyl hydrolase family 94 (GH94), which only comprises GPs, is one of the most studied GP families that have been used as biocatalysts for carbohydrate synthesis, in academic research and in industrial production. Understanding the mechanism of GH94 enzymes is a crucial step towards enzyme engineering to improve and expand the applications of these enzymes in synthesis. In this work with a GH94 laminaribiose phosphorylase from Paenibacillus sp. YM‐1 (PsLBP), we have demonstrated an enzymatic synthesis of disaccharide 1 (β‐d‐mannopyranosyl‐(1→3)‐d‐glucopyranose) by using a natural acceptor glucose and noncognate donor substrate α‐mannose 1‐phosphate (Man1P). To investigate how the enzyme recognises different sugar 1‐phosphates, the X‐ray crystal structures of PsLBP in complex with Glc1P and Man1P have been solved, providing the first molecular detail of the recognition of a noncognate donor substrate by GPs, which revealed the importance of hydrogen bonding between the active site residues and hydroxy groups at C2, C4, and C6 of sugar 1‐phosphates. Furthermore, we used saturation transfer difference NMR spectroscopy to support crystallographic studies on the sugar 1‐phosphates, as well as to provide further insights into the PsLBP recognition of the acceptors and disaccharide products.
TL;DR: 6 disaccharides were detected and identified, indicating the existence of polysaccharides constructed of corresponding repeateddisaccharide fragments in C. sinensis, demonstrating a potential strategy to characterize mixed poly Saccharides without separation and purification.
TL;DR: Photoinitiated addition of thiols to 2-deoxy-exo-glycals obtained from endo- glycals of d-arabino, d-lyxo,d-erythro and d-threo configurations resulted in highly regio- and stereoselective formation of glycosylmethyl sulfide type glycomimetics.
Abstract: A series of 2-deoxy-glycopyranosyl cyanides with D-arabino, D-lyxo, D-erythro, and D-threo configurations was synthesized from the corresponding glycals via 2-deoxy-glycopyranosyl acetates. The cyanides were transformed to anhydro-aldose tosylhydrazones by reduction with NaH2PO2/Ra-Ni in the presence of tosylhydrazine. The tosylhydrazones furnished 2-deoxy-exo-glycals under modified Bamford–Stevens conditions. Photoinitiated thiol–ene additions of these exo-glycals resulted in the corresponding C-(2-deoxy-D-glycopyranosyl)methyl sulfides in medium to good yields with exclusive regio- and stereoselectivities in most cases. Several disaccharide mimics with a C–S moiety in place of the glycosidic oxygen were also obtained.
TL;DR: Evaluation of the synthetic compounds for their ability to act as microbe-associated molecular patterns in plants, through induction of reactive oxygen species, was investigated and suggested that the immunologically silent nature of the natural glycans is due to specific structural features.
Abstract: The synthesis of bradyrhizose, the monosaccharide component of the lipopolysaccharide O-antigen of the nitrogen-fixing bacteria Bradyrhizobium sp. BTAi1 and sp. ORS278, has been achieved in 25 steps in an overall yield of 6% using myo-inositol and ethyl propiolate as the starting materials. The route involved the late-stage resolution of a racemic intermediate to provide both enantiomers of this unusual bicyclic monosaccharide. Both the natural d-enantiomer, and the unnatural and heretofore unknown l-enantiomer, were converted to disaccharide derivatives containing different forms of the monosaccharide (d,d; l,l; d,l; l,d). Evaluation of the synthetic compounds for their ability to act as microbe-associated molecular patterns in plants, through induction of reactive oxygen species, was investigated. These experiments suggest that the immunologically silent nature of the natural glycans is due to specific structural features.
TL;DR: Cryomicroscopy showed that sucrose was a more effective disaccharide additive to suppress nucleation and growth of ice crystals that occurred during devitrification in concentrated glycerol solutions, despite the excellent inhibitory ability of trehalose on ice growth that has been confirmed in many researches.
TL;DR: The results emphasize the relevance of glycans in bioinorganic chemistry and underpin a fundamental molecular description of the HS-Pt interactions that alter the profile of platinum agents from cytotoxic to metastatic in a systematic manner.
Abstract: We report herein a detailed NMR study of the aquation and subsequent covalent binding of the trinuclear clinical agent [{trans-PtCl(15NH3)2}2{μ-trans-Pt(15NH3)2(15NH2(CH2)615NH2)2}]4+ (1, 1,0,1/t,t,t or Triplatin) with three d-glucosamine residues containing varied O-sulfate and N-sulfate or N-acetyl substitutions, which represent monosaccharide fragments present within the repeating disaccharide sequences of cell surface heparan sulfate (HS). The monosaccharides GlcNS(6S), GlcNS, and GlcNAc(6S) were synthesized in good yield from a common 4,6-diol α-methyl glucopyranoside intermediate. The reactions of 15N-1 with sodium sulfate, GlcNS(6S), GlcNS, and GlcNAc(6S) were followed by 2D [1H,15N] heteronuclear single quantum coherence (HSQC) NMR spectroscopy using conditions (298 K, pH ≈5.4) similar to those previously used for other anionic systems, allowing for a direct comparison. The equilibrium constants (pK1) for the aquation of 1 in the presence of GlcNS(6S) and GlcNS were slightly higher compared to tha...
TL;DR: Comparing small-angle neutron scattering data on myoglobin in aqueous solutions of either sucrose or trehalose is compared to investigate their effect on protein–protein interactions and it is found that both tre Halose and sucrose induces a well-defined protein-protein distance, which could explain why these inhibit protein– protein interactions and associated protein aggregation.
Abstract: The disaccharide trehalose has shown outstanding anti-aggregation properties for proteins, which are highly important for the possibility to treat neurodegenerative diseases, such as Alzhei...
TL;DR: Calculation and analysis of the intermolecular nuclear Overhauser effect, nuclear quadrupole relaxation, dielectric relaxation spectroscopy, and first shell residence times at room temperature yield further insights into the hydration dynamics of different sugars and confirm that trehalose slows down water dynamics to a slightly larger extent than other sugars.
Abstract: The bioprotective nature of monosaccharides and disaccharides is often attributed to their ability to slow down the dynamics of adjacent water molecules. Indeed, solvation dynamics close to sugars is indisputably retarded compared to bulk water. However, further research is needed on the qualitative and quantitative differences between the water dynamics around different saccharides. Current studies on this topic disagree on whether the disaccharide trehalose retards water to a larger extent than other isomers. Based on molecular dynamics simulation of the time-dependent Stokes shift of a chromophore close to the saccharides trehalose, sucrose, maltose, and glucose, this study reports a slightly stronger retardation of trehalose compared to other sugars at room temperature and below. Calculation and analysis of the intermolecular nuclear Overhauser effect, nuclear quadrupole relaxation, dielectric relaxation spectroscopy, and first shell residence times at room temperature yield further insights into the hydration dynamics of different sugars and confirm that trehalose slows down water dynamics to a slightly larger extent than other sugars. Since the calculated observables span a wide range of timescales relevant to intermolecular nuclear motion, and correspond to different kinds of motions, this study allows for a comprehensive view on sugar hydration dynamics.
TL;DR: This study is the first to identify the substrate (unsaturated hyaluronan disaccharide) recognized and imported by the streptococcal PTS and shed light on bacterial clever colonization/infection system targeting various animal polysaccharides.
Abstract: Certain bacterial species target the polysaccharide glycosaminoglycans (GAGs) of animal extracellular matrices for colonization and/or infection. GAGs such as hyaluronan and chondroitin sulfate consist of repeating disaccharide units of uronate and amino sugar residues, and are depolymerized to unsaturated disaccharides by bacterial extracellular or cell-surface polysaccharide lyase. The disaccharides are degraded and metabolized by cytoplasmic enzymes such as unsaturated glucuronyl hydrolase, isomerase, and reductase. The genes encoding these enzymes are assembled to form a GAG genetic cluster. Here, we demonstrate the Streptococcus agalactiae phosphotransferase system (PTS) for import of unsaturated hyaluronan disaccharide. S. agalactiae NEM316 was found to depolymerize and assimilate hyaluronan, whereas its mutant with a disruption in the PTS genes included in the GAG cluster was unable to grow on hyaluronan, while retaining the ability to depolymerize hyaluronan. Using toluene-treated wild-type cells, the PTS activity for import of unsaturated hyaluronan disaccharide was significantly higher than that observed in the absence of the substrate. In contrast, the PTS mutant was unable to import unsaturated hyaluronan disaccharide, indicating that the corresponding PTS is the only importer of fragmented hyaluronan, which is suitable for PTS to phosphorylate the substrate at the C-6 position. This is distinct from Streptobacillus moniliformis ATP-binding cassette transporter for import of sulfated and non-sulfated fragmented GAGs without substrate modification. The three-dimensional structure of streptococcal EIIA, one of the PTS components, was found to contain a Rossman-fold motif by X-ray crystallization. Docking of EIIA with another component EIIB by modeling provided structural insights into the phosphate transfer mechanism. This study is the first to identify the substrate (unsaturated hyaluronan disaccharide) recognized and imported by the streptococcal PTS. The PTS and ABC transporter for import of GAGs shed light on bacterial clever colonization/infection system targeting various animal polysaccharides.
TL;DR: This approach provides a critical tetrasaccharide intermediate for subsequent chemoenzymatic transformation to fondaparinux and its analogues.
TL;DR: The results suggested the combination of two mutations, V407M and K490L, was conducive for the production of trehalose, and the self‐inducible TreSV407M/K490L mutant in the B. subtilis host provides a low‐cost choice for the industrial production of endotoxin‐free tre Halose with high yields.
Abstract: Trehalose is a nonreducing disaccharide synthesized by trehalose synthase (TreS), which catalyzes the reversible interconversion of maltose and trehalose. We aimed to enhance the catalytic conversion of maltose to trehalose by saturation mutagenesis, and constructed a self-inducible TreS expression system by generating a robust Bacillus subtilis recombinant. We found that the conversion yield and enzymatic activity of TreS was enhanced by saturation mutations, especially by the combination of V407M and K490L mutations. At the same time, these saturation mutations were contributing to reducing by-products in the reaction. Compared to WT TreS, the conversion yield of maltose to trehalose was increased by 11.9%, and the kcat /Km toward trehalose was 1.33 times higher in the reaction catalyzed by treSV407M-K490L . treSV407M-K490L expression was further observed in the recombinant B. subtilis W800N(ΔσF ) under the influence of PsrfA , Pcry3Aa , and PsrfA-cry3Aa promoters without an inducer. It was shown that PsrfA-cry3Aa was evidently a stronger promoter for treSV407M-K490L expression, with the intracellular enzymatic activity of recombinant treSV407M-K490L being over 5,800 U/g at 35 hr in TB medium. These results suggested the combination of two mutations, V407M and K490L, was conducive for the production of trehalose. In addition, the self-inducible TreSV407M/K490L mutant in the B. subtilis host provides a low-cost choice for the industrial production of endotoxin-free trehalose with high yields.
TL;DR: An efficient multi-gram synthesis of bleomycin disaccharide has been developed, and its conjugate with 10-HCPT displayed obvious selectivity, clearly indicating the potential of bleomers in solving the targeted therapy of cytotoxic drugs.
Abstract: The “tumor-seeking” role of bleomycin (BLM) disaccharide has been demonstrated to serve as a promising tool for cancer diagnosis and a potential ligand for targeted therapy. However, these practical applications are often hampered by the lack of BLM disaccharide. Herein, an efficient multi-gram synthesis of peracetylated BLM disaccharide 20 is achieved by a TMSOTF-mediated glycosidation coupling manner in 43.6% overall yield in terms of benzyl galactoside. The critical innovation of the synthetic strategy is that inexpensive benzyl galactoside was first adopted to prepare an L-gulose subunit 3 as a glycosyl acceptor, with a much shorter route in 73.0% yield, and a 3-O-carbamoyl-mannose donor 4 was achieved in 47.2% yield by lowering the amount of dibutyltin oxide, and merging aminolysis and selective deacetylation into a one-pot reaction. Next, the incorporation of BLM disaccharide into 10-hydroxycamptothecin (10-HCPT), a non-specific model compound, to form conjugate 1 could significantly improve the antitumor activity and display obvious selectivity toward cancerous and normal cells in comparison with 10-HCPT. Moreover, BLM disaccharide itself was non-cytotoxic, clearly indicating the importance and potential of BLM disaccharide in solving the targeted antitumor therapy of cytotoxic drugs.
TL;DR: The key step for the synthesis was the glycosylation coupling of a stereodirecting donor with a configuration‐stable TMS glycoside acceptor and either the donor or acceptor could be substituted with an azido group.
Abstract: A general strategy for the diverse synthesis of ten disaccharide aminoglycosides, including natural 2-trehalosamine (1), 3-trehalosamine (2), 4-trehalosamine (3), and neotrehalosyl 3,3'-diamine (8) and synthetic aminoglycosides 4-7, 9, and 10, has been developed. The aminoglycoside compounds feature different anomeric configurations and numbers of amino groups. The key step for the synthesis was the glycosylation coupling of a stereodirecting donor with a configuration-stable TMS glycoside acceptor. Either the donor or acceptor could be substituted with an azido group. The aminoglycosides prepared in the present study were characterized by 1D and 2D NMR spectroscopy.
TL;DR: The OH-initiated heterogeneous oxidation of mixed saccharide aqueous aerosols is investigated using an atmospheric-pressure flow tube coupled to off-line analysis of the particle composition to discuss the possible effect of the disaccharide surface partitioning on the heterogeneous kinetics.
Abstract: The OH-initiated heterogeneous oxidation of mixed saccharide aqueous aerosols is investigated using an atmospheric-pressure flow tube coupled to off-line analysis of the particle composition. For equimolar monosaccharide/disaccharide aqueous aerosol mixtures, the decay of the disaccharide is found to be significantly slower than that of the monosaccharide. Molecular dynamics simulations of the mixed aqueous solutions reveal the formation of a ∼10 A disaccharide exclusion layer below the water surface. A simple chemical model is developed to discuss the possible effect of the disaccharide surface partitioning on the heterogeneous kinetics. The observed decays are consistent with a poor spatial overlap of the OH radical at the interface with the disaccharide in the particle bulk. The effect of partitioning on the heterogeneous oxidation of atmospheric organic aerosols is discussed.
TL;DR: The Manβ(1 → 4)GlcNAc disaccharide may be used as a key intermediate for elaboration into more complex N- glycan structures providing a route to N-glycan oxazolines as donor substrates for ENGase enzymes that is considerably shorter than those reported previously.
01 Oct 2019
TL;DR: For the dehydration of fructose in water, heparin–PEI@PDA@MWCNT exhibits advantages over published heterogeneous catalysts on the basis of HMF yield and HMF selectivity.
Abstract: Being a member of the glycosaminoglycan family of carbohydrates, native heparin is a highly sulfated polysaccharide. Herein, heparin was grafted onto polydopamine (PDA)- and poly(ethylene imine) (PEI)-coated multiwalled carbon nanotubes (MWCNTs) (heparin-PEI@PDA@MWCNT). The immobilized heparin consists of a sulfated repeating disaccharide unit, conferring a unique microenvironment when catalyzing fructose dehydration into 5-hydroxymethylfurfural (HMF). The hydrogen bonding interactions naturally occur between the disaccharide unit of heparin and the monosaccharide fructose, and the adjacent sulfonic acid groups catalyze the fructose dehydration. The reactions were performed in water, and heparin-PEI@PDA@MWCNT achieved an HMF yield of 46.2% and an HMF selectivity of 82.2%. For the dehydration of fructose in water, heparin-PEI@PDA@MWCNT exhibits advantages over published heterogeneous catalysts on the basis of HMF yield and HMF selectivity. Three aspects contribute to the environmentally benign processing: (1) the catalyst heparin is a natural sulfated polysaccharide; (2) the catalysis is carried out in water and not in organic solvents; and (3) fructose can be produced from a biomass resource.
TL;DR: The first construction of the challenging β-(1 → 5)-linked GalNAc-Kdo skeleton is described for the synthesis of the disaccharide antigen of the capsular polysaccharide of Kingella kingae KK01 in excellent yield with satisfactory β-selectivity.
Abstract: The first construction of the challenging β-(1 → 5)-linked GalNAc-Kdo skeleton is described for the synthesis of the disaccharide antigen of the capsular polysaccharide of Kingella kingae KK01. TfOH-catalyzed glycosylation of N-Troc-protected D-galactosaminyl N-phenyl trifluoroacetimidate with a sterically hindered 5-hydroxyl group of the β-Kdo building block in toluene proceeded smoothly to provide the desired disaccharide in excellent yield with satisfactory β-selectivity. An optimal sequence for the deprotection of the disaccharide skeleton was found to access the disaccharide antigen of Kingella kingae KK01 for further immunological studies.