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Abstract N -glycosylation on the crystallizable fragment (Fc) governs antibody-mediated immune responses. This study addressed the relevance of N -acetylglucosamine (GlcNAc)-bisected IgG 1 on the disease progression and treatment efficacy in the immune active phase of chronic hepatitis B virus (HBV) infection. Serum IgG 1 N -glycan patterns from 166 HBV e antigen (HBeAg)-positive patients were analyzed using liquid chromatography-tandem mass spectrometry. The proportion of GlcNAc-bisected IgG 1 on the disease severity and efficacy of nucleos(t)ide analogue treatment were investigated. Cytokine-dependent regulations of IgG 1 GlcNAc bisection were also addressed using mouse IgG 1 -producing hybridoma cells. We found that IgG 1 bearing a fully galactosyl-fucosyl- N -acetylglucosamine-bisected (G2FN) glycoform in HBeAg-positive patients was associated with high levels of HBV DNA or HBV surface antigen, alanine aminotransferase <2 upper limits of normal, and a mild liver injury. Moreover, baseline IgG 1 -G2FN ≧ 1.5% was linked to lower probabilities of virological response (HBV DNA undetectable in serum), HBeAg seroconversion, HBV core antigen loss, and liver histological improvement after treatment. Cox and logistic regression analyses revealed that IgG 1 -G2FN was an unfavorable factor for the virological response (hazard ratio = 0.620, 95% confidence interval = 0.466–0.825, P = 0.001) or liver histological improvement (odds ratio = 0.513, 95% confidence interval = 0.279–0.943, P = 0.032), respectively. Results from in vitro studies showed that transforming growth factor (TGF)-β1 treatment downregulated mannosyl β-1,4- N -acetylglucosaminyltransferase 3 and β-1,4-galactosyltransferase 1 activities and thereby IgG 1 -G2FN production, and this phenomenon reflected an inverse correlation between IgG 1 -G2FN and TGF-β1 in sera of patients (r = −0.431, P < 0.001). In conclusion, IgG 1 -G2FN was related to an attenuated liver inflammation and unfavorable treatment responses in patients with HBeAg-positive chronic hepatitis B. Highlights • IgG 1 -G2FN glycoform was inversely correlated with the severity of liver inflammation and fibrosis in HBeAg-positive CHB. • An unfavorable anti-HBV treatment efficacy was seen in patients with a high serum IgG 1 -G2FN level at baseline. • Transforming growth factor-β1 is a pivotal regulator for IgG 1 -G2FN. • IgG 1 -G2FN connects intricate interplays among HBV virology, host humoral immunity, and liver fibrogenesis. [ABSTRACT FROM AUTHOR]

The mutants of the tumor suppressor protein p53 form protein aggregates. It has been proposed that these aggregates propagate like prions, albeit the detailed mechanism of the propagation is unclear. Our recent study revealed that sulfated glycosaminoglycans, especially highly sulfated domains of heparan sulfate (heparan sulfate S-domains), participate in cancer pathology by mediating transcellular propagation of p53 aggregates. [ABSTRACT FROM AUTHOR]

Abstract Mammary s erine p rotease in hibitor or Maspin has been characterized as a class II tumor suppressor gene in several cancer types, among them prostate cancer (CaP). Androgen ablation is an effective therapy for CaP, but with short-term effectiveness, thus new therapeutic strategies are actively sought. The present study is aimed to explore the effects of a glucosamine derivative, 2-(N-Carbobenzyloxy) l -phenylalanylamido-2-deoxy-β- d -glucose (NCPA), on two CaP cell lines, PC3 and LNCaP. In particular we analyzed the impact of NCPA on Maspin production, cell viability and cell cycle progression and apoptosis/necrosis pathway activation in PC3 and LNCaP cell lines. NCPA is able to stimulate Maspin production in PC3 and not in LNCaP cell lines. NCPA blocks the PC3 cell cycle in G1 phase, by inhibiting Cyclin D1 production and induces the apoptosis, therefore interfering with aggressiveness of this androgen-insensitive cell line. Moreover, NCPA is able to induce the expression of Maspin in LNCaP cell line treated with androgen receptor inhibitor, Bicalutamide, and in turn to stimulate the apoptosis of these cells. These findings suggest that NCPA, stimulating the endogenous production of a tumor suppressor protein, could be useful in the design of new therapeutic strategies for treatment of CaP. Highlights • NCPA stimulates Maspin production in PC3 prostate cancer cells inducing apoptosis. • NCPA does not stimulate Maspin production in LNCaP prostate cancer cells. • Administration of Bicalutamide plus NCPA induces Maspin and apoptosis in LNCaP cells. • Administration of Bicalutamide plus NCPA results in a synergistic effect. • Our findings highlight the possibility of a use of NCPA as a chemosensitizing agent. [ABSTRACT FROM AUTHOR]

We report the synthesis and characterization of Cu 2 O nanoparticles (NPs) in the presence of the coordinating ligands like l -glutamic acid (Glu-Cu 2 O) and d -glucosamine (GlcN-Cu 2 O). Even if –NH 2 group is common to both the ligands, l -glutamic acid is a straight chain compound containing additional two –COOH groups, whereas, glucosamine is a cyclic compound with additional four –OH groups and an ether (-O-) linkage. Thus the coordinating ligands are different in the nature of the functional groups as well as their molecular skeletons leading to cubic morphology (∼350 nm of average edge length) for l -glutamic acid coordinated Cu 2 O and spherical morphology (∼250 nm of average diameter) for glucosamine one as observed by Field Effective Scanning Electron Microscopy (FE-SEM) and Transmission Electron Microscopy (TEM) images. The observed band gap of Cu 2 O of 1.89 eV is decreased to 1.84 ev for both the ligated structures. Both the ligated cuprous oxide (Cu 2 O) nanoparticles (NPs) were used for the photocatalytic degradation of methylene Blue (MB). The spherical GlcN-Cu 2 O showed 98% degradation of MB in 105 min and after 3 cycles of operation, the photocatalytic activity was enough for the 93% degradation of the dye, whereas, the cubic Gu-Cu 2 O could degrade MB up to 97% in 135 min and after three cycles, only 86% of the dye was degraded. This indicates, the molecular skeleton and functional groups on the ligand control the shape and size of the Cu 2 O nanoparticles as well as the photocatalytic efficiency and stability. It is presumed, the cyclic glucosamine ligand can protect the Cu 2 O nanoparticles from erosion during the degradation process. [ABSTRACT FROM AUTHOR]

The title compounds were synthesized from the selectively protected N -acylated d -glucosamine derivatives, containing α-halo carboxylic acid moieties, via intramolecular 3- O -alkylation. It was found that if the starting compound contains asymmetric electrophilic center, isomuramic acid derivatives were mainly formed, regardless of the configuration of the electrophilic carbon atom. An explanation for the observed stereochemical results was proposed on the basis of the analysis of steric interactions in the molecules of the starting compounds, as well as using the concept of anchimeric assistance. It was shown that N -acetylation of the obtained lactam derivatives and subsequent methanolysis under mild conditions led to the selective cleavage of δ-lactam ring resulting in the formation of the corresponding ester derivatives of N -acetylmuramic acid or its analogues in high yields. [ABSTRACT FROM AUTHOR]

Sugar based low molecular weight gelators (LMWGs) are useful small molecules that can form reversible supramolecular gels with many applications. Selective functionalization of common monosaccharides has resulted in several classes of effective LMWGs. Recently we found that certain peracetylated sugars containing anomeric triazole functional groups were effective gelators. In this study we synthesized two series of 4,6- O -benzylidene acetal protected β-1,2,3-triazolyl glycoside of D-glucose and N -acetyl D-glucosamine derivatives and evaluated their self-assembling properties in a few solvents. Several gelators were obtained and the gelation properties of these compounds rely on the structures of the 4-triazolyl substituents. Typically, alkyl derivatives resulted in effective gelation in organic solvents and aqueous mixtures of ethanol and dimethyl sulfoxide. But further acetylation of these compounds resulted in loss of gelation properties. The gels were characterized using optical microscopy, rheology, and FTIR spectroscopy. We also analyzed the molecular assemblies, using 1 H NMR spectroscopy to probe the influences of the hydroxyl, amide, and triazole functional groups. Naproxen was used as a model drug and it formed co-gels with compound 25 in DMSO water mixtures. Using UV spectroscopy, we found that naproxen was slowly released from the gel to aqueous solution. The general structure and gelation trend obtained here can be useful in designing sugar based biomaterials. We expect that further structural optimization can lead to more effective gelators that are compatible with different drug molecules for encapsulation and sustained release. [ABSTRACT FROM AUTHOR]

Glucosamine is a monomer of chitin/chitosan, which is a renewable aquatic resource and the second most abundant biopolymer on the Earth. Moreover, methanesulfonic acid (MSA) is known as an eco-friendly green catalyst. In this study, the MSA-catalyzed conversion of glucosamine to levulinic (LA) and formic (FA) acids was optimized using the Box-Behnken statistical approach. The optimal conditions for LA yield were 50 g/L glucosamine, 0.5 M MSA, 200 °C and 30 min, which yielded 49.9% LA and 50.8% FA. The LA yield increased linearly with increasing combined severity factor (CSF) until 3.5 and then, was maintained as the CSF value was further increased. The FA yield behaved similarly to LA. Both trends fitted well to a sigmoid regression model with a high regression value. These results highlight the potential of glucosamine for biofuel and chemicals production via an MSA-catalyzed conversion system. [ABSTRACT FROM AUTHOR]

Finding products with antiapoptotic activities has been one of the approaches for the treatment of neurodegenerative disorders. Serum/glucose deprivation (SGD) has been used as a model for the investigation of the molecular mechanisms of neuronal ischemia. Recent studies indicated that glucosamine (GlcN) and N-acetyl glucosamine (GlcNAc) have many pharmacological effects including antioxidant activities. The present study aimed to investigate the protective effects of GlcN and GlcNAc against SGDinduced PC12 cells injury. The PC12 cells were pretreated with GlcN and GlcNAc for 2 h, and then exposed to SGD for 6, 12 and 24 h. Cell viability was evaluated by MTT assay. The level of intracellular reactive oxygen species (ROS) was determined by flow cytometry using 2',7'- dichlorofluorescin diacetate (DCFHDA) as a probe. SGD condition caused a significant reduction in cell survival after 6, 12, and 24 h (P < 0.001). Pretreatment with GlcN and GlcNAc (0.6-20 mM) increased cell viability following SGD insult. A significant increase in cell apoptosis was observed in cells under SGD condition after 12 h (P < 0.001). Pretreatment with GlcN and GlcNAc (5-20 mM) decreased apoptosis following SGD condition after 12 h. SGD resulted in a significant increase in intracellular ROS production after 12 h. Pretreatment with both amino sugars at concentrations of 10 to 20 mM could reverse the ROS increment. Results indicated that GlcN and GlcNAc had a cytoprotective property against SGD-induced cell death via anti-apoptosis and antioxidant activities, suggesting that these aminosugers have the potential to be used as novel therapeutic agents for neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

A new N , N -dimethyl- d -glucosamine ligand has been developed for the copper-catalyzed Ullmann-type coupling of N -H heterocycles (e.g., indoles, benzimidazoles, pyrazoles and triazoles) with aryl halides. This method was accomplished not only featuring excellent yields, mild reaction conditions and simple operation, but also showing eco-friendly and broad-spectrum substrates, and could be widely used in the construction of N -aryl heterocyclic systems. [ABSTRACT FROM AUTHOR]

A series of novel or known water-soluble derivatives of chiral gossypol were synthesized and screened in vitro for their anti-HIV-1 activity. (−)-gossypol derivative was more active against HIV-1 than the corresponding (+)-gossypol derivative, respectively. Among these derivatives, d -glucosamine derivative of (−)-gossypol, oligopeptide derivative of (−)-gossypol and taurine derivative of (−)-gossypol, such as compounds 1a , 3a and 14a , showed significant inhibitory activities against HIV-1 replication, HIV-1 mediated cell-cell fusion and HIV gp41 6-helix bundle formation as some amino acid derivatives of (−)-gossypol. [ABSTRACT FROM AUTHOR]

To administer cancer drugs with improved convenience to patients and to enhance the bioavailability of cancer drugs for oral cancer therapy, this study prepared gellan gum/glucosamine/clioquinol (GG/GS/CQ) film as the oral cancer treatment patch. GG/GS/CQ film fabricated through the EDC-mediated coupling reactions (GG/GS/CQ/EDC film). The film of the physicochemical properties and drug release kinetics were studied. The effectiveness of GG/GS/CQ/EDC film as oral cancer treatment patch were evaluated with the animal model. The results confirmed that CQ can be incorporated via EDC-mediated covalent conjugation to gellan gum/glucosamine. Mechanical testing revealed that the maximum tensile strength and elongation percentage at break were 1.91 kgf/mm 2 and 5.01% for GG/GS/CQ/EDC film. After a drug release experiment lasting 45 days, 86.8% of CQ was released from GG/GS/CQ/EDC film. The Huguchi model fit the GG/GS/CQ/EDC drug release data with high correlation coefficients (R 2 = 0.9994, respectively). The effect of the CQ dose on oral cancer cells (OC-2) was tested, and the IC 50 of CQ alone and CQ with 10 μM CuCl 2 were 9.59 and 2.22 μM, respectively. The animal testing indicated that GG/GS/CQ/EDC film was decreased epidermal growth factor receptor (EGFR) expression and suppress tumor progression. These findings provide insights into a possible use for GG/GS/CQ/EDC film for oral ca in clinical practice. The GG/GS/CQ/EDC film is suitable as the dressing for use in the treatment of early-stage cancer or as wound care after surgery in late-stage of oral cancer treatment. [ABSTRACT FROM AUTHOR]

Positive and negative ion high-resolution electrospray ionization mass spectra (MS and MS2) of cyclooligo-β-(1→6)-D-glucosamines and cyclooligo-β-(1→6)-N-acetyl-D-glucosamines were acquired and interpret. It was shown that the cleavages of glycosidic bonds are the main processes in the decay of protonated and metallated molecules. In addition, elimination of the water molecules (and ammonia for cyclooligo-β-(1→6)-D-glucosamines) was observed along with other processes including the unknown skeletal rearrangement. A primary fragmentation of the negatively charged ions (deprotonated molecules) differed from that of the positively charged ones. [ABSTRACT FROM AUTHOR]

Chitosan, a β-1,4-linked glucosamine polymer is formed by deacetylation of chitin. It has a wide range of applications from agriculture to human health care products. Chitosan is commercially produced from shellfish, shrimp waste, crab and lobster processing using strong alkalis at high temperatures for long time periods. The production of chitin and chitosan from fungal sources has gained increased attention in recent years due to potential advantages in terms of homogenous polymer length, high degree of deacetylation and solubility over the current marine source. Zygomycetous fungi such as Absidia coerulea, Benjaminiella poitrasii, Cunninghamella elegans, Gongrenella butleri, Mucor rouxii, Mucor racemosus and Rhizopus oryzae have been studied extensively. Isolation of chitosan are reported from few edible basidiomycetous fungi like Agaricus bisporus, Lentinula edodes and Pleurotus sajor-caju. Other organisms from mycotech industries explored for chitosan production are Aspergillus niger, Penicillium chrysogenum, Saccharomyces cerevisiae and other wine yeasts. Number of aspects such as value addition to the existing applications of fungi, utilization of waste from agriculture sector, and issues and challenges for the production of fungal chitosan to compete with existing sources, metabolic engineering and novel applications have been discussed to adjudge the potential of fungal sources for commercial chitosan production. [ABSTRACT FROM AUTHOR]

6-Sulfo-6-deoxy-D-glucosamine (GlcN6S), 6-sulfo-6-deoxy-D-glucosaminitol (ADGS) and their N -acetyl and methyl ester derivatives have been synthesized and tested as inhibitors of enzymes catalyzing reactions of the UDP-GlcNAc pathway in bacteria and yeasts. GlcN6S and ADGS at micromolar concentrations inhibited glucosamine-6-phosphate (GlcN6P) synthase of microbial origin. The former was also inhibitory towards fungal GlcN6P N-acetyl transferase, but at millimolar concentrations. Both compounds and their N -acetyl derivatives exhibited antimicrobial in vitro activity, with MICs in the 0.125–2.0 mg mL −1 range. Antibacterial but not antifungal activity of GlcN6S was potentiated by D-glucosamine and a synergistic antibacterial effect was observed for combination of ADGP and a dipeptide Nva-FMDP. [ABSTRACT FROM AUTHOR]

Production of renewable chemicals with established market and high value is highly desirable in biomass utilization. Herein, glucosamine, an amino sugar with various applications, was generated in a single step by the acid-catalyzed transformation of chitin. Aprotic polar solvents were mixed with water to promote the hydrolysis as well as the deacetylation reactions, significantly enhancing product yield and/or reducing the concentration and amount of acid catalyst required. By employing the optimized co-solvent system, glucosamine was achieved with 80% yield at 175 °C in 1h from ball-milled chitin, in sharp contrast with the pure water system with the same acid concentration in which less than 1% glucosamine was obtained. Correlations between the promotional effect and various solvent property parameters were discussed and proposed, providing guidance on the choice of solvent for further optimization of the co-solvent system for similar applications. [ABSTRACT FROM AUTHOR]

Corals harbor symbiotic dinoflagellates, Symbiodinium spp., acquired from surrounding environments. Because Symbiodinium are present at low densities in the water column, corals may attract these symbionts using chemotactic compounds. To examine whether corals contain chemotactic compounds, we established an assay to measure the chemotactic activity for Symbiodinium using an extract of the coral Acropora tenuis, a major reef-building coral in Japan. Our assay revealed that Symbiodinium strain NBRC102920 (clade A), which is taken up by juvenile A. tenuis polyps, is attracted to crude A. tenuis extracts. We found that the chemotactic compounds are water-soluble, heat-labile macromolecules and that the chemotactic activity was inhibited by N-acetyl- d-glucosamine (GlcNAc). We separated the GlcNAc-binding fraction (Fr-ActL) and identified it as the most plausible candidate for the chemoattractant, since the chemotactic activity of the crude A. tenuis extract appeared to be mainly attributable to the activity of Fr-ActL and was also inhibited by the addition of GlcNAc. These results indicate that chemoattraction is mediated via the binding of Symbiodinium to Fr-ActL. [ABSTRACT FROM AUTHOR]

Chronic inflammation has been associated to cancer development by the alteration of several inflammatory pathways, such as Nuclear Factor-κB pathway. In particular, IκB kinase α (IKKα), one of two catalytic subunit of IKK complex, has been described to be associated to cancer progression and metastasis in a number of cancers. The molecular mechanism by which IKKα affects cancer progression is not yet completely clarified, anyway an association between IKKα and the expression of Maspin (Mammary Serine Protease Inhibitor or SerpinB5), a tumor suppressor protein, has been described. IKKα shuttles between cytoplasm and nucleus, and when is localized into the nuclei, IKKα regulates the expression of several genes, among them Maspin gene, whose expression is repressed by high amount of nuclear IKKα. Considering that high levels of Maspin have been associated with reduced metastatic progression, it could be hypothesized that the repression of IKKα nuclear translocation could be associated with the repression of metastatic phenotype. The present study is aimed to explore the ability of a glucosamine derivative, 2-( N -Carbobenzyloxy) l -phenylalanylamido-2-deoxy-β- d -glucose (NCPA), synthesized in our laboratory, to stimulate the production of Maspin in an osteosarcoma cell line, 143B. Immunofluorescence and Western blotting experiments showed that NCPA is able to inhibit IKKα nuclear translocation, and to stimulate Maspin production. Moreover, in association with stimulation of Maspin production we found the decrease of β1 Integrin expression, the down-regulation of metalloproteases MMP-9 and MMP-13 production and cell migration inhibition. Taking in account that β1 Integrin and MMP-9 and -13 have been correlated with the invasiveness of osteosarcoma, considering that NCPA affects the invasiveness of 143B cell line, we suggest that this molecule could affect the osteosarcoma metastatic ability. [ABSTRACT FROM AUTHOR]

O-GlcNAc transferase (OGT) is a key enzyme involved in dynamic O-GlcNAcylation of nuclear and cytoplasmic proteins similar to phosphorylation. Discovery of cell-permeable OGT inhibitors is significant to clarify the function and regulatory mechanism of O-GlcNAcylation. This will establish the foundation for the development of therapeutic drugs for relevant diseases. Here, we report two cell-permeable OGT inhibitors (APNT and APBT), developed from low-activity precursors (IC50 > 1 mM) via "tethering in situ click chemistry (TISCC)". Both of them were able to inhibit O-GlcNAcylation in cells without significant effects on cell viability. Unusual noncompetitive inhibition of OGT was helpful to discover novel inhibitors and explore the regulatory mechanism of OGT. The development of these molecules validates that TISCC can be utilized to discover novel lead compounds from components that exhibited very weak binding to the target. [ABSTRACT FROM AUTHOR]

Glycosylation is one of the most common and important post-translational modifications, influencing both the chemical and the biological properties of proteins. Studying the glycosylation of the entire protein population of a sample can be challenging because variations in the concentrations of certain proteins can enhance or obscure changes in glycosylation. Furthermore, alterations in the glycosylation pattern of individual proteins, exhibiting larger variability in disease states, have been suggested as biomarkers for different types of cancer, as well as inflammatory and neurodegenerative diseases. In this paper, we present a rapid and efficient method for glycosylation analysis of individual proteins focusing on changes in the degree of fucosylation or other alterations to the core structure of the glycans, such as the presence of bisecting N -acetylglucosamines and a modified degree of branching. Streptavidin-coated magnetic beads are used in combination with genetically engineered immunoaffinity binders, called VHH antibody fragments. A major advantage of the VHHs is that they are nonglycosylated; thus, enzymatic release of glycans from the targeted protein can be performed directly on the beads. After deglycosylation, the glycans are analyzed by MALDI-TOF-MS. The developed method was evaluated concerning its specificity, and thereafter implemented for studying the glycosylation pattern of two different proteins, alpha-1-antitrypsin and transferrin, in human serum and cerebrospinal fluid. To our knowledge, this is the first example of a protein array-type experiment that employs bead-based immunoaffinity purification in combination with mass spectrometry analysis for fast and efficient glycan analysis of individual proteins in biological fluid. [ABSTRACT FROM AUTHOR]

Three amidoquinoline-naphthalimide dyads are designed and synthesized in 67–73% overall yields in 3 steps from commercially available starting materials. Compounds with unsubstituted and nitro naphthalimide (1 and 2) show excellent selective fluorescent responses towards glucosamine with the enhancement of fluorescence quantum yields by 14 folds. The determination of HOMO-LUMO levels by linear sweep voltammetry suggests that the sensing mechanism likely involves the inhibition of photo-induced electron transfer (PET) between the aminoquinoline and naphthalimide moieties by glucosamine. The association constants of 1.55×10 4 and 1.45×10 4 M − 1 , along with the glucosamine detection limits of 1.06 and 0.29 µM are determined for 1 and 2, respectively. The application of 2 as a fluorescent probe for real-time detection of cellular glucosamine at micromolar level in living Caco-2 cells is also demonstrated. [ABSTRACT FROM AUTHOR]

Herein we report the synthesis of 3-aminopropyl glycosides of A (type 2) and B (type 2) tetrasaccharides via [3 + 1] block scheme. Peracetylated trichloroacetimidates of A and B trisaccharides were used as glycosyl donors. The well-known low reactivity of 4-OH group of N-acetyl- d -glucosamine forced us to test four glucosamine derivatives (3-Bz-1,6-anhydro-GlcNAc and 3-trifluoroacetamidopropyl β-glycosides of 3-Ac-6-Bn-GlcNAc, 3-Ac-6-Bn-GlcN 3 , and 3-Ac-6-Bn-GlcNAc 2 ) to select the best glycosyl acceptor for the synthesis of type 2 tetrasaccharides. The desired tetrasacchrides were not isolated, when 3-trifluoroacetamidopropyl glycosyde of 3-Ac-6-Bn-GlcNAcβ was glycosylated. Glycosylation of 3-Bz-1,6-anhydro-GlcNAc derivative resulted in α-glycoside as a major product. High stereospecificity was achieved only in the synthesis of B (type 2) tetrasaccharide, when 3-trifluoroacetamidopropyl 3-Ac-6-Bn-GlcNAc 2 β was applied as the glycosyl acceptor (β/α 5:1), whereas glycosylation with trichloroacetimidate of A trisaccharide was not stereospecific (β/α 1.3:1). Glycosylation of 3-trifluoroacetamidopropyl glycoside of 3-Ac-6-Bn-GlcN 3 β with trichloroacetimidates of A and B trisaccharides provided the same stereochemical yield (β/α 1.5:1). [ABSTRACT FROM AUTHOR]

Ethacrynic acid (EA), a known inhibitor of the neoplastic marker glutathione S -transferase P1 and other GSTs, exerts a weak antiproliferative activity against human cancer cells. The clinical use of EA (Edecrin) as an anticancer drug is limited by its potent loop diuretic activity. In this study, we developed a non-diuretic 2-amino-2-deoxy- d -glucose conjugated EA (EAG) to target tumors cells via the highly expressed glucose transporter 1 (GLUT1). Cell survival assays revealed that EAG had little effect on normal cells, but was cytotoxic 3 to 4.5-fold greater than EA. Mechanistically, the EAG induced selective cell death in cancer cells by inhibiting GSTP1 and generating abundant reactive oxygen species. Furthermore, EAG induced p21 cip1 expression and a G2/M cell cycle block irrespective of the p53 gene status in tumor cells. These data encourage the development of new EA analogs. [ABSTRACT FROM AUTHOR]

A rapid high performance liquid chromatographic method with evaporative light scattering detection (HPLC-ELSD), using a carbohydrate column, was developed for simultaneous determination of N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) in dairy foods. Sample preparation was performed by precipitation using acetonitrile. The limits of detection were 2.097 mg/L for GlcNAc and 3.247 mg/L for GalNAc. The limits of quantification were 6.043 mg/L for GlcNAc and 9.125 mg/L for GalNAc. Accuracy ranged from 96.4 to 105.7% for GlcNAc and from 97.1 to 104.1% for GalNAc. The precision of the method was <1.7% for GlcNAc and <2.2% for GalNAc. The mean recovery of the method was measured by spiking samples with 30.0–120.0 mg/L GlcNAc or 12.5–50.0 mg/L GalNAc and was found to be 95.1–105.5% for GlcNAc and 99.5–105.9% for GalNAc. The stability test results of standard solutions stored at 4, 20, and 40°C were 96.2–104.7% for GlcNAc and 98.0–106.5% for GalNAc. This study determined GlcNAc and GalNAc in dairy foods using HPLC-ELSD method. This rapid, simultaneous quantitation method might be useful as a mean of convenient quality control of dairy foods. [ABSTRACT FROM AUTHOR]

O-Linked N-acetylglucosamine, or O-GlcNAc, is a dynamic post-translational modification that cycles on and off serine and threonine residues of nucleocytoplasmic and mitochondrial proteins. In addition to cancer and inflammation diseases, O-GlcNAc modification appears to play a critical role during cell apoptosis and stress response, although the precise mechanisms are still not very clear. Here we found that nitric oxide synthase adaptor (NOS1AP), which plays an important part in glutamate-induced neuronal apoptosis, carries the modification of O-GlcNAc. Mass spectrometry analysis identified Ser47, Ser183, Ser204, Ser269, Ser271 as O-GlcNAc sites. Higher O-GlcNAc of NOS1AP was detected during glutamate-induced neuronal apoptosis. Furthermore, with O-GlcNAc sites of NOS1AP mutated, the interaction of NOS1AP and neuronal nitric oxide syntheses (nNOS) decreases. Finally, during glutamate-induced neuronal apoptosis, decreasing the O-GlcNAc modification of NOS1AP results in more severe neuronal apoptosis. All these results suggest that O-GlcNAc modification of NOS1AP exerts protective effects during glutamate-induced neuronal apoptosis. [ABSTRACT FROM AUTHOR]

An efficient, catalyst-free methodology has been developed for the Michael addition reaction between D-glucosamine derivatives and various Michael acceptors. All reactions proceeded smoothly at room temperature to furnish novel sugar-derived vinylogous carbamates in high chemical yields and excellent stereoselectivity. [ABSTRACT FROM AUTHOR]

The covalent attachment of O-linked β- N-acetylglucosamine ( O-GlcNAc) to Ser/Thr residues of proteins acts as not only a posttranslational modification but also a nutritional sensor in nucleus and cytoplasm, which directly regulates the expression of genes and multiple crucial signal transduction pathways. Dynamic O-GlcNAcylation at Ser/Thr residues is catalyzed by two key enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase, which are responsible for addition and removal of the O-GlcNAc modification, respectively. O-GlcNAc modification plays important roles in cellular signaling in animals, especially in human diseases. Two orthologs of OGT in plants, SECRET AGENT and SPINDLY, have been reported to be involved in diverse plant processes. However, compared with the functional mechanisms revealed in animals, the consequences of protein O-GlcNAc modification in plants is largely unknown, and the relationship between O-GlcNAcylation and cellular processes needs to be explored. In this review, we summarized the recent advances on O-GlcNAc modification and its biological functions in animals and plants, and prospect of more special functions of O-GlcNAc will be revealed in plants. [ABSTRACT FROM AUTHOR]

A new 4-hydroxy glycosyl acceptor derivative of d-glucosamine containing a lactam-type N-protecting group was synthesized. The new glycosyl acceptor containing a hydroxy group at the C(4) atom was shown to be highly reactive in the glycosylation despite the presence of the amide (lactam) NH group. The high efficiency of the synthesized acceptor derivative is apparently attributed to the transformation of the ( Z)-amide function that is present in amino sugar derivatives containing an acyclic acyl N-protecting group into the ( E)-amide group in derivatives containing a lactam-type cyclic N-protecting group. This transformation leads to a radical change in the hydrogen bonding conditions and the character of molecular association. The observed effect can be employed to design new N-protecting groups providing high reactivity of glycosyl acceptor derivatives of D-glucosamine. [ABSTRACT FROM AUTHOR]

The article provides an assessment of the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) expression in tumors. Topics included an overview of OGT glycosyltransferase, the significant role of O-GlcNAcylation in non-alcoholic liver disease hepatocellular carcinoma pathogenesis (NAFLD-HCC), and the role of OGT NAFLD-HCC.

Fondaparinux, a synthetic pentasaccharide based on the heparin antithrombin-binding domain, is an approved clinical anticoagulant. Although it is a better and safer alternative to pharmaceutical heparins in many cases, its high cost, which results from the difficult and tedious synthesis, is a deterrent for its widespread use. The chemical synthesis of fondaparinux was achieved in an efficient and concise manner from commercially available D-glucosamine, diacetone α- D-glucose, and penta-O-acetyl- D-glucose. The method involves suitably functionalized building blocks that are readily accessible and employs shared intermediates and a series of one-pot reactions that considerably reduce the synthetic effort and improve the yield. [ABSTRACT FROM AUTHOR]

A glycosylated and cross-linked caseinate ( GCC) with glucosamine amount of 4.74 g/kg protein was generated from caseinate and oligochitosan by a microbial transglutaminase. The applied temperature, pH and molar ratio of acyl donor/acceptor were 37 °C, 7.5 and 1:3, respectively; while caseinate concentration, transglutaminase addition and reaction time selected from single-factor trials were 50 g/L, 10 kU/kg protein and 3 h, respectively. Electrophoretic analysis revealed the cross-linking and glycosylation of caseinate. Compared with caseinate, GCC showed improved solubility in pH 4-11, higher digestibility in vitro and water binding capacity, about 3-fold, but lower surface hydrophobicity and oil binding capacity (34%). [ABSTRACT FROM AUTHOR]

2,3,4,6-tetra-O-Acetyl-D-gluconic acid was synthesized and coupled with 1,3,4, 6-tetra-O-acetyl-2-amino-2-deoxy-β-D-glucopyranose and diosgenyl 3,4,6-tri-O-acetyl-2-amino-2-deoxy-β-D-glucopyranoside to affordN-gluconyl derivatives of diosgenyl 2-amino-2-deoxy-D-glucopyranoside using the methods of solution-phase peptide synthesis. Both coupling reactions suffered from acetylO→Nmigration, which caused theN-acetyl derivatives to be formed together with theN-(D-gluconyl) derivatives of D-glucosamine. Additionally, single-crystal X-ray diffraction and high-resolution NMR spectral data for 2,3,4,6-tetra-O-acetyl-D-gluconic acid were analyzed to reveal that this acyclic carbohydrate has adopted the2G−conformation instead of a typical zigzag conformation. The planarity andcisgeometry of the acetoxyl groups are demonstrated. [ABSTRACT FROM AUTHOR]

Highlights: [•] The reactivity of both anomers of 6-O-protected allosamine and glucosamine acceptors with a superarmed donor was assessed. [•] Glucosamine derivatives react with the same selectivity as with disarmed donors, i.e. driven by electronic effects. [•] Allosamine derivatives react exclusively by the equatorial O-4, i.e. driven by steric factors. [Copyright &y& Elsevier]

Abstract: Glucosamine (GlcN) and its acetylated derivative, N-acetylglucosamine (GlcNAc), are widely used in nutraceutical and pharmaceutical industries. Currently, GlcN and GlcNAc are mainly produced by hydrolysis from crab and shrimp shells, which can cause severe environmental pollution and carries the potential risk of allergic reactions. In this study, we attempted to achieve microbial production of GlcNAc by pathway engineering of Bacillus subtilis 168. Specifically, glmS (encoding GlcN-6-phosphate synthase) from B. subtilis 168 and GNA1 (encoding GlcNAc-6-phosphate N-acetyltransferase) from Saccharomyces cerevisiae S288C were firstly co-overexpressed in B. subtilis; the level of GlcNAc reached 240mg/L in shake flask culture. Next, nagP, encoding the GlcNAc-specific enzyme of phosphotransferase system, was deleted to block the importation of extracellular GlcNAC, thus improving GlcNAc production to 615mg/L in shake flask culture. Then, nagA (encoding GlcNAc-6-phosphate deacetylase), gamA (encoding GlcN-6-phosphate deaminase), and nagB (encoding GlcN-6-phosphate deaminase) were deleted to block the catabolism of intracellular GlcNAc, thereby further increasing the GlcNAc titer to 1.85g/L in shake flask culture. Finally, microbial production of GlcNAc by the engineered B. subtilis 168 was conducted in a 3-L fed-batch bioreactor, and the GlcNAc titer reached 5.19g/L, which was 2.8-fold of that in shake flask culture. This is the first report regarding the pathway engineering of B. subtilis for microbial production of GlcNAc, and provides a good starting point for further metabolic engineering to achieve the industrial production of GlcNAc by a generally regarded as safe strain. [Copyright &y& Elsevier]

Two deoxyglucose (DG) derivatives, (α,β)-2-deoxy-2-amino(ethylcarbamate)-D-glucose (ECB-DG) and (α,β)-2-deoxy-2-amino(1,2-dihydroxypropyl)-D-glucose (DHP-DG), were synthesized and radiolabeled successfully with [99mTc(H2O)3(CO)3]+ complex. [99mTc]-ECBDG and [99mTc]-DHP-DG complexes were prepared (96% and 93% radiochemical purities respectively) by using 46 mCi of Na99mTcO4 in 1 mL saline. Radio-HPLC analysis of [99mTc]- ECB-DG at pH = 7.4, revealed that labeling with 99mTc leads to formation of one radiochemical species with tR = 381 second. Three radiochemical species, Na99mTcO4, [99mTc]-DHP-DG and [99mTc(H2O)3(CO)3]+ complexes with tR = 342 sec, tR = 567 sec and tR = 1586 sec respectively, were obtained when [99mTc]-DHP-DG complex evaluated by HPLC. Biodistribution of two complexes were studied on normal mice at 10, 30 and 60 min post-injections. Compared to the 18F-FDG, [99mTc]-ECB-DG displayed a 2.8-fold reduction in brain uptake (1.7 ± 0.2 versus 0.61% ± 0.09) ,whereas [99mTc]-DHP-DG just showed 1.9-fold reduction in heart uptake (2.2 ± 0.05 towards 1.16±0.10) at 1 h post-injection. On the basis of our results, it seems that ECB-DG and DHP-DG analogues could be used as brain and heart imaging agent respectively [ABSTRACT FROM AUTHOR]

A series of D-glucosamine derivatives were synthesized (2-4) and evaluated for their antimicrobial activity. Some of the compounds investigated have shown significant antimicrobial activity against Gram-positive and Gram-negative bacterial strains as well as a few fungal strains. The results suggest that the presence of sugar moiety is necessary to biological activity. [ABSTRACT FROM AUTHOR]

Abstract: Aspergillus flavus is the second most common cause of aspergillosis infection in immunocompromised patients and is responsible for the production of aflatoxins. Little is known about the population structure of A. flavus, although recent molecular and phenotypic data seem to demonstrate that different genetic lineages exist within this species. The aim of this study was to carry out a morphological, physiological, and molecular analysis of a set of clinical and environmental isolates to determine whether this variability is due to species divergence or intraspecific diversity, and to assess whether the clinical isolates form a separate group. The amdS and omtA genes were more phylogenetically informative than the other tested genes and their combined analysis inferred three main clades, with no clear distinction between clinical and environmental isolates. No important morphological and physiological differences were found between the members of the different clades, with the exception of the assimilation of d-glucosamine, which differentiates the members of the clade II from the others. [Copyright &y& Elsevier]

Abstract: Introduction: The diagnosis of infection and the ability to distinguish bacterial infection from nonbacterial inflammation by positron emission tomography (PET) have gained interest in recent years, but still few specific radiopharmaceuticals are available for use. In this study, we developed a new radiosynthesis method of 2-deoxy-2-[18F]fluoroacetamido-d-glucopyranose ([18F]FAG) by applying microwave irradiation and demonstrated that [18F]FAG could be a potential radiopharmaceutical to distinguish bacterial infection from nonbacterial inflammation. Methods: 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-bromoacetamido-d-glucopyranose was used as precursor, and labeling was performed under microwave irradiation conditions followed by alkaline hydrolysis and high-performance liquid chromatography (HPLC) purification. In vitro uptake of [18F]FAG by Escherichia coli was performed. Tissue biodistribution of [18F]FAG was performed in mice. Moreover, PET imaging acquisition of E. coli infection and nonbacterial inflammation models was performed in rats. Tissue radiotracer-accumulated sites were analyzed by hematoxylin and eosin staining and anti–E.coli immunostaining. Results: The radiosynthesis of [18F]FAG was achieved with microwave irradiation, and the radiochemical yield was 9.7%±2.8% end of bombardment (EOB); the radiochemical purity was more than 98%, and the total synthesis time was 62 min. Compared with control group, in vitro uptake of [18F]FAG by E. coli was significantly decrease in inhibition group (P<.05). Biodistribution studies in mice showed rapid clearance of [18F]FAG from the animal body. [18F]FAG clearly visualized the infection areas but not nonbacterial inflammation areas in PET studies. Quantitative analysis revealed that the uptake of [18F]FAG into infection areas was significantly higher than that of [18F]FAG into inflammation areas (P<.05). Histological analysis demonstrated the presence of bacterial cells at the sites of accumulation of [18F]FAG. Conclusions: Using 1,3,4,6-tetra-O-acetyl-2-deoxy-2-bromoacetamido-d-glucopyranose as a precursor, the new radiosynthesis method of [18F]FAG was achieved in fewer steps and with a shorter synthesis time than previously reported. Furthermore, [18F]FAG was able to distinguish bacterial infection from nonbacterial inflammation. [Copyright &y& Elsevier]

Abstract: N-Acetylglucosaminylinositol (GlcNAc-Ins)-deacetylase (MshB) and mycothiol-S-conjugate amidase (Mca), structurally related amidases present in mycobacteria and other Actinomycetes, are involved in the biosynthesis of mycothiol and in the detoxification of xenobiotics as their mycothiol-S-conjugates, respectively. With substrate analogs of GlcNAc-Ins, MshB showed a marked preference for inositol as the aglycon present in GlcNAc-Ins. The inhibition of MshB and Mca by 10 thioglycosides, 7 cyclohexyl-2-deoxy-2-C-alkylglucosides, and 4 redox cyclers was evaluated. The latter contained plumbagin tethered via 2 to 5 methylene carbons and an amide linkage to phenyl-2-deoxy-2-amino-1-thio-α-d-glucopyranoside. These proved to be the most potent amongst the 21 compounds tested as inhibitors of MshB. Their inhibitory potency varied with the length of the spacer, with the compound with longest spacer being the most effective. [Copyright &y& Elsevier]

Abstract: The coupling reactions of d-glucosamine, 1,3,4,6-tetra-O-acetylglucosamine, and 4-aminophenyl-galactopyranosine with N,N-bis(quinolinoyl)aminovaleric acid (L1) provided a series of conjugates containing a potentially tridentate donor group terminus linked to a sugar moiety, L2′, L2 and L3, respectively. Reactions of the ligands with [NEt4]2[Re(CO)3Br3] in refluxing methanol provided the rhenium complexes [Re(CO3)(L1)]Br (ReL1), [Re(CO)3(L2)]Br (ReL2), [Re(CO)3(L2′)]Br (ReL2′) and [Re(CO)3(L3)]Br (ReL3). The ligands and complexes were characterized by elemental analyses, 1H and 13C NMR, mass spectroscopy and, in the case of L1 and ReL1, by X-ray crystallography. The rhenium complexes exhibit fluorescence emissions with long lifetimes, large Stokes shifts, and moderate quantum yields. [Copyright &y& Elsevier]

A highly efficient CH3CN-promoted hexamethyldisilazane per-O-trimethylsilylation of amino sugars was developed. Its applications in homogenous N-functionalisation and a concise synthesis of glucosamine 6-phosphate are described. [ABSTRACT FROM AUTHOR]

An efficient procedure for the reductive opening of 4,6-O-benzylidene acetals was established under microfluidic conditions. 4,6-O-Benzylidene acetals of the glucose, glucosamine, and galactose derivatives were selectively converted into the corresponding 4- or 6-O-benzyl derivatives in nearly quantitative yields. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA), the most prevalent degenerative joint disease, still lacks a true disease-modifying therapy. The involvement of the NF-κB pathway and its upstream activating kinases in OA pathogenesis has been recognized for many years. The ability of the N-acetyl phenylalanine glucosamine derivative (NAPA) to increase anabolism and reduce catabolism via inhibition of IKKα kinase has been previously observed in vitro and in vivo. The present study aims to confirm the chondroprotective effects of NAPA in an in vitro model of joint OA established with primary cells, respecting both the crosstalk between chondrocytes and synoviocytes and their phenotypes. This model satisfactorily reproduces some features of the previously investigated DMM model, such as the prominent induction of ADAMTS-5 upon inflammatory stimulation. Both gene and protein expression analysis indicated the ability of NAPA to counteract key cartilage catabolic enzymes (ADAMTS-5) and effectors (MCP-1). Molecular analysis showed the ability of NAPA to reduce IKKα nuclear translocation and H3Ser10 phosphorylation, thus inhibiting IKKα transactivation of NF-κB signalling, a pivotal step in the NF-κB-dependent gene expression of some of its targets. In conclusion, our data confirm that NAPA could truly act as a disease-modifying drug in OA. [ABSTRACT FROM AUTHOR]

A diagram is presented which shows the D-glucosamines catalyst-free Michael addition to acetylenic and vinylic compounds and the access to vinylogous carbamates of the derivatives of D-Glucosamine.

The D-glucosamine derivative (III) is efficiently transformed into oxazolidinone of D-xylosamine (IV), D-allosamine and D-ribosamine. [ABSTRACT FROM AUTHOR]