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Molecules (Basel, Switzerland) May 2023Drug leads with a high Fsp index are more likely to possess desirable properties for progression in the drug development pipeline. This paper describes the development...
Diastereoselective Synthesis of the Borylated d-Galactose Monosaccharide 3-Boronic-3-Deoxy-d-Galactose and Biological Evaluation in Glycosidase Inhibition and in Cancer for Boron Neutron Capture Therapy (BNCT).
Drug leads with a high Fsp index are more likely to possess desirable properties for progression in the drug development pipeline. This paper describes the development of an efficient two-step protocol to completely diastereoselectively access a diethanolamine (DEA) boronate ester derivative of monosaccharide d-galactose from the starting material 1,2:5,6-di--isopropylidene-α-d-glucofuranose. This intermediate, in turn, is used to access 3-boronic-3deoxy-d-galactose for boron neutron capture therapy (BNCT) applications. The hydroboration/borane trapping protocol was robustly optimized with BH.THF in 1,4-dioxane, followed by in-situ conversion of the inorganic borane intermediate to the organic boron product by the addition of DEA. This second step occurs instantaneously, with the immediate formation of a white precipitate. This protocol allows expedited and greener access to a new class of BNCT agents with an Fsp index = 1 and a desirable toxicity profile. Furthermore, presented is the first detailed NMR analysis of the borylated free monosaccharide target compound during the processes of mutarotation and borarotation.
Topics: Humans; Monosaccharides; Galactose; Boron; Boron Neutron Capture Therapy; Neoplasms; Boranes; Boron Compounds
PubMed: 37298796
DOI: 10.3390/molecules28114321 -
Scientific Reports Mar 2016The recognition of cancer cells is a key for cancer diagnosis and therapy, but the specificity highly relies on the use of biorecognition molecules particularly...
The recognition of cancer cells is a key for cancer diagnosis and therapy, but the specificity highly relies on the use of biorecognition molecules particularly antibodies. Because biorecognition molecules suffer from some apparent disadvantages, such as hard to prepare and poor storage stability, novel alternatives that can overcome these disadvantages are highly important. Here we present monosaccharide-imprinted fluorescent nanoparticles (NPs) for targeting and imaging of cancer cells. The molecularly imprinted polymer (MIP) probe was fluorescein isothiocyanate (FITC) doped silica NPs with a shell imprinted with sialic acid, fucose or mannose as the template. The monosaccharide-imprinted NPs exhibited high specificity toward the target monosaccharides. As the template monosaccharides used are over-expressed on cancer cells, these monosaccharide-imprinted NPs allowed for specific targeting cancer cells over normal cells. Fluorescence imaging of human hepatoma carcinoma cells (HepG-2) over normal hepatic cells (L-02) and mammary cancer cells (MCF-7) over normal mammary epithelial cells (MCF-10A) by these NPs was demonstrated. As the imprinting approach employed herein is generally applicable and highly efficient, monosaccharide-imprinted NPs can be promising probes for targeting cancer cells.
Topics: Fluorescein-5-isothiocyanate; Hep G2 Cells; Humans; MCF-7 Cells; Molecular Imprinting; Monosaccharides; Nanoparticles; Neoplasms; Silicon Dioxide
PubMed: 26948803
DOI: 10.1038/srep22757 -
Biochemistry. Biokhimiia Jul 2013High-performance anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD) is an established technique for the carbohydrate analysis of glycoproteins.... (Review)
Review
High-performance anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD) is an established technique for the carbohydrate analysis of glycoproteins. HPAE-PAD is routinely used for determinations of monosaccharide, sialic acid, mannose-6-phosphate (M-6-P), and oligosaccharide contents of a glycoprotein. This is true for both the initial investigation of a glycoprotein and routine assays of recombinant therapeutic glycoproteins. This contribution reviews the fundamentals of HPAE-PAD, recent technological improvements, and advances in the last ten years in its application to carbohydrate analysis of glycoproteins. The application areas reviewed include monosaccharide determinations, sialic acid determinations, M-6-P determinations, sugar alcohol determinations, analysis of polysialic acids, neutral and charged oligosaccharide analysis, following glycosidase and glycosyltransferase reactions, and coupling HPAE-PAD to mass spectrometry (MS).
Topics: Carbohydrates; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Electrochemical Techniques; Glycoproteins; Mannosephosphates; Mass Spectrometry; Monosaccharides; Oligosaccharides; Sialic Acids
PubMed: 24010833
DOI: 10.1134/S000629791307002X -
Molecules (Basel, Switzerland) Dec 2013Quinochalcone C-glycosides are regarded as characteristic components that have only been isolated from the florets of Carthamus tinctorius. Recently, quinochalcone... (Review)
Review
Quinochalcone C-glycosides are regarded as characteristic components that have only been isolated from the florets of Carthamus tinctorius. Recently, quinochalcone C-glycosides were found to have multiple pharmacological activities, which has attracted the attention of many researchers to explore these compounds. This review aims to summarize quinochalcone C-glycosides' physicochemical properties, chromatographic behavior, spectroscopic characteristics, as well as their biological activities, which will be helpful for further study and development of quinochalcone C-glycosides.
Topics: Animals; Carthamus tinctorius; Chalcone; Glycosides; Humans; Molecular Structure; Monosaccharides; Quinones
PubMed: 24335575
DOI: 10.3390/molecules181215220 -
Journal of Nanobiotechnology Apr 2022Effective and accurate screening of oncological biomarkers in peripheral blood circulation plays an increasingly vital role in diagnosis and prognosis. High-sensitivity...
BACKGROUND
Effective and accurate screening of oncological biomarkers in peripheral blood circulation plays an increasingly vital role in diagnosis and prognosis. High-sensitivity assays can effectively aid clinical decision-making and intervene in cancer in a localized status before they metastasize and become unmanageable. Meanwhile, it is equally pivotal to prevent overdiagnosis of non-life-threatening cancer by eliminating unnecessary treatment and repeated blood draws. Unfortunately, current clinical screening methodologies can hardly simultaneously attain sufficient sensitivity and specificity, especially under resource-restrained circumstances. To circumvent such limitations, particularly for cancer biomarkers from early-onset and recurrence, we aim to develop a universal plasmonic platform for clinical applications, which macroscopically amplifies multiplexed fluorescence signals in a broad spectral window and readily adapts to current assay setups without sophisticated accessories or expertise at low cost.
METHODS
The plasmonic substrate was chemically synthesized in situ at the solid-liquid interface by rationally screening a panel of reducing monosaccharides and tuning the redox reactions at various catalyst densities and precursor concentrations. The redox properties were studied by Benedict's assay and electrochemistry. We systemically characterized the morphologies and optical properties of the engineered plasmonic Ag structures by scanning electron microscopy (SEM) and spectroscopy. The structure-fluorescence enhancement correlation was explicitly explained by the finite-difference time-domain (FDTD) simulation and a computational model for gap distribution. Next, we established an enhanced fluoroimmunoassay (eFIA) using a model biomarker for prostate cancer (PCa) and validated it in healthy and PCa cohorts. Prognosis was explored in patients subject to surgical and hormonal interventions following recommended PCa guidelines.
RESULTS
The monosaccharide-mediated redox reaction yielded a broad category of Ag structures, including sparsely dispersed nanoparticles (NPs) of various sizes, semi-continuous nanoislands, and crackless continuous films. Optimal broad-spectral fluorescence enhancement from green to far-red was observed for the inhomogeneous, irregularly-shaped semi-continuous Ag nanoisland substrate (AgNIS), synthesized from a well-balanced redox reaction at a stable rate mediated by mannose. In addition, different local electric field intensity distributions in response to various incident excitations were observed at the nanoscale, elucidating the need for irregular and inhomogeneous structures. AgNIS enabled a maximized 54.7-fold macroscopically amplified fluorescence and long-lasting photostability. Point-of-care availability was fulfilled using a customized smartphone prototype with well-paired optics. The eFIA effectively detected the PCa marker in cell lines, xenograft tumors, and patient sera. The plasmonic platform rendered a diagnostic sensitivity of 86.0% and a specificity of 94.7% and capably staged high-grade PCa that the clinical gold standard test failed to stratify. Patient prognosis of robotic-assisted surgeries and hormone therapies was non-invasively monitored following efficient medical interventions. The assay time was significantly curtailed on the plasmonic platform upon microwave irradiation.
CONCLUSIONS
By investigating the effects of reducing monosaccharides on the seed-mediated chemical synthesis of plasmonic Ag structures, we deduced that potent multiplexed fluorescence enhancement originated from both an adequate reducing power and a steady reduction rate. Furthermore, the inhomogeneous structure with adequate medium gap distances afforded optimal multiwavelength fluorescence enhancement, thus empowering an effective eFIA for PCa. The clinically validated diagnostic and prognostic features, along with the low sample volume, point-of-care feasibility with a smartphone, and microwave-shortened assay time, warrant its potential clinical translation for widespread cancer biomarker analysis.
Topics: Biomarkers, Tumor; Fluorescence; Humans; Male; Monosaccharides; Nanoparticles; Prostatic Neoplasms
PubMed: 35399094
DOI: 10.1186/s12951-022-01359-z -
PloS One 2019Sudangrass, Sorghum sudanense (Piper) Stapf, is a vigorous forage crop that has also been used for biogas, paper, and electricity production. Due to the large biomass...
Sudangrass, Sorghum sudanense (Piper) Stapf, is a vigorous forage crop that has also been used for biogas, paper, and electricity production. Due to the large biomass yields achieved by sudangrass and the large area of potential growth in Argentina seven sudangrass accessions from a collection of S. sudanense were analyzed to evaluate their potential as feedstocks for lignocellulosic bioethanol production, and to assess whether there is an association between the response to biotic and abiotic stresses and the composition of the biomass. The biomass composition was analyzed for major cell wall polymers, monosaccharides, and elemental composition. On average, 68% of stem lignocellulosic biomass was comprised of matrix polysaccharides and crystalline cellulose, representing a potential source of sugars for bioethanol production. Xylose was the predominant matrix polysaccharide monosaccharide comprising, on average, 45% of the total sugars, followed by arabinose, glucose, galactose, galacturonic acid, mannose, glucuronic acid, and fucose. Rhamnose was not detected in any of the biomasses analyzed. Silica was the most abundant element in sudangrass stem, followed by chloride, calcium, phosphorus and sulfur. We performed saccharification analyses after pretreatments. Alkaline pretreatment was more effective than water pretreatment. Sodium hydroxide pretreatment exposed different levels of recalcitrance among sudangrass accessions, whereas the water pretreatment did not. Phenological traits were also evaluated, showing significant variability among accessions. The comparison of major cell wall polymers and monosaccharide composition between tolerant and susceptible accessions to abiotic and biotic stresses suggests an association between the composition of the biomass and the response to stress.
Topics: Argentina; Bioelectric Energy Sources; Biomass; Cell Wall; Ethanol; Lignin; Monosaccharides; Polysaccharides; Sorghum; Stress, Physiological
PubMed: 31120985
DOI: 10.1371/journal.pone.0217435 -
European Journal of Biochemistry Apr 2004Collectins are a family of collagenous calcium-dependent defense lectins in animals. Their polypeptide chains consist of four regions: a cysteine-rich N-terminal domain,... (Review)
Review
Collectins are a family of collagenous calcium-dependent defense lectins in animals. Their polypeptide chains consist of four regions: a cysteine-rich N-terminal domain, a collagen-like region, an alpha-helical coiled-coil neck domain and a C-terminal lectin or carbohydrate-recognition domain. These polypeptide chains form trimers that may assemble into larger oligomers. The best studied family members are the mannan-binding lectin, which is secreted into the blood by the liver, and the surfactant proteins A and D, which are secreted into the pulmonary alveolar and airway lining fluid. The collectins represent an important group of pattern recognition molecules, which bind to oligosaccharide structures and/or lipid moities on the surface of microorganisms. They bind preferentially to monosaccharide units of the mannose type, which present two vicinal hydroxyl groups in an equatorial position. High-affinity interactions between collectins and microorganisms depend, on the one hand, on the high density of the carbohydrate ligands on the microbial surface, and on the other, on the degree of oligomerization of the collectin. Apart from binding to microorganisms, the collectins can interact with receptors on host cells. Binding of collectins to microorganisms may facilitate microbial clearance through aggregation, complement activation, opsonization and activation of phagocytosis, and inhibition of microbial growth. In addition, the collectins can modulate inflammatory and allergic responses, affect apoptotic cell clearance and modulate the adaptive immune system.
Topics: Animals; Bacterial Proteins; Carbohydrates; Collectins; Epitopes; Fungal Proteins; Humans; Immune System; Inflammation; Lipids; Models, Biological; Monosaccharides; Polysaccharides; Protein Binding; Protein Structure, Tertiary; Viral Proteins
PubMed: 15030473
DOI: 10.1111/j.1432-1033.2004.04040.x -
Glycobiology Oct 2020Saccharides in our diet are major sources of carbon for the formation of biomass such as proteins, lipids, nucleic acids and glycans. Among the dietary monosaccharides,...
Saccharides in our diet are major sources of carbon for the formation of biomass such as proteins, lipids, nucleic acids and glycans. Among the dietary monosaccharides, glucose occupies a central role in metabolism, but human blood contains regulated levels of other monosaccharides as well. Their influence on metabolism and how they are utilized have not been explored thoroughly. Applying metabolic flux analysis on glycan synthesis can reveal the pathways that supply glycosylation precursors and provide a snapshot of the metabolic state of the cell. In this study, we traced the incorporation of six 13C uniformly labeled monosaccharides in the N-glycans, O-glycans and glycosphingolipids of both pluripotent and neural NTERA-2 cells. We gathered detailed isotopologue data for hundreds of glycoconjugates using mass spectrometry methods. The contributions of de novo synthesis and direct incorporation pathways for glucose, mannose, fructose, galactose, N-acetylglucosamine and fucose were determined based on their isotope incorporation. Co-feeding studies revealed that fructose incorporation is drastically decreased by the presence of glucose, while mannose and galactose were much less affected. Furthermore, increased sialylation slowed down the turnover of glycans, but fucosylation attenuated this effect. Our results demonstrated that exogenous monosaccharide utilization can vary markedly depending on the cell differentiation state and monosaccharide availability, and that the incorporation of carbons can also differ among different glycan structures. We contend that the analysis of metabolic isotope labeling of glycans can yield new insights about cell metabolism.
Topics: Glycocalyx; Humans; Monosaccharides; Neural Stem Cells; Pluripotent Stem Cells
PubMed: 32337579
DOI: 10.1093/glycob/cwaa038 -
Scientific Reports Jun 2016It remains particularly difficult for gaining unambiguous information on anomer, linkage, and position isomers of oligosaccharides using conventional mass spectrometry...
It remains particularly difficult for gaining unambiguous information on anomer, linkage, and position isomers of oligosaccharides using conventional mass spectrometry (MS) methods. In our laboratory, an ion mobility (IM) shift strategy was employed to improve confidence in the identification of structurally closely related disaccharide and monosaccharide isomers using IMMS. Higher separation between structural isomers was achieved using 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatization in comparison with phenylhydrazine (PHN) derivatization. Furthermore, the combination of pre-IM fragmentation of PMP derivatives provided sufficient resolution to separate the isomers not resolved in the IMMS. To chart the structural variation observed in IMMS, the collision cross sections (CCSs) for the corresponding ions were measured. We analyzed nine disaccharide and three monosaccharide isomers that differ in composition, linkages, or configuration. Our data show that coexisting carbohydrate isomers can be identified by the PMP labeling technique in conjunction with ion-mobility separation and tandem mass spectrometry. The practical application of this rapid and effective method that requires only small amounts of sample is demonstrated by the successful analysis of water-soluble ginseng extract. This demonstrated the potential of this method to measure a variety of heterogeneous sample mixtures, which may have an important impact on the field of glycomics.
Topics: Antipyrine; Disaccharides; Edaravone; Free Radical Scavengers; Monosaccharides; Spectrometry, Mass, Electrospray Ionization; Staining and Labeling; Tandem Mass Spectrometry
PubMed: 27306514
DOI: 10.1038/srep28079 -
Journal of Chemical Theory and... Jun 2018We present an extension of the CHARMM Drude polarizable force field to enable modeling of polysaccharides containing pyranose and furanose monosaccharides. The new force...
We present an extension of the CHARMM Drude polarizable force field to enable modeling of polysaccharides containing pyranose and furanose monosaccharides. The new force field parameters encompass 1↔2, 1→3, 1→4, and 1→6 pyranose-furanose linkages, 2→1 and 2→6 furanose-furanose linkages, 2→2, 2→3, and 2→4 furanose-pyranose, and 1↔1, 1→2, 1→3, 1→4, and 1→6 pyranose-pyranose linkages. For the glycosidic linkages, both simple model compounds and the full disaccharides with methylation at the reducing end were used for parameter optimization. The model compounds were chosen to be monomers or glycosidic-linked dimers of tetrahydropyran (THP) and tetrahydrofuran (THF). Target data for optimization included one- and two-dimensional potential energy scans of ω and the Φ/Ψ glycosidic dihedral angles in the model compounds and full disaccharides computed by quantum mechanical (QM) RIMP2/cc-pVQZ single point energies on MP2/6-31G(d) optimized structures. Also included in the target data are extensive sets of QM gas phase monohydrate water-saccharide interactions, dipole moments, and molecular polarizabilities for both model compounds and full disaccharides. The resulting polarizable model is shown to be in good agreement with a range of QM data, offering a significant improvement over the additive CHARMM36 carbohydrate force field, as well as experimental data including crystal structures and conformational properties of disaccharides and a trisaccharide in aqueous solution.
Topics: Algorithms; Furans; Glycosides; Molecular Dynamics Simulation; Monosaccharides; Polysaccharides; Pyrans; Quantum Theory; Thermodynamics; Water
PubMed: 29694037
DOI: 10.1021/acs.jctc.8b00175