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The Journal of Biological Chemistry 2021The elongated antennae decorating eukaryotic glycans are built from polylactosamine repeats. Polylactosamine forms a lectin recognition site and also acts as a platform...
The elongated antennae decorating eukaryotic glycans are built from polylactosamine repeats. Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity. Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis. The resulting insights will also help decipher other members of GT31, the single largest human glycosyltransferase family.
Topics: Amino Sugars; Glycosylation; N-Acetylglucosaminyltransferases; Polysaccharides
PubMed: 33453284
DOI: 10.1016/j.jbc.2020.100212 -
Cancer Letters Apr 2024O-linked-N-acetylglucosaminylation (O-GlcNAcylation), a dynamic post-translational modification (PTM), holds profound implications in controlling various cellular... (Review)
Review
O-linked-N-acetylglucosaminylation (O-GlcNAcylation), a dynamic post-translational modification (PTM), holds profound implications in controlling various cellular processes such as cell signaling, metabolism, and epigenetic regulation that influence cancer progression and therapeutic resistance. From the therapeutic perspective, O-GlcNAc modulates drug efflux, targeting and metabolism. By integrating signals from glucose, lipid, amino acid, and nucleotide metabolic pathways, O-GlcNAc acts as a nutrient sensor and transmits signals to exerts its function on genome stability, epithelial-mesenchymal transition (EMT), cell stemness, cell apoptosis, autophagy, cell cycle. O-GlcNAc also attends to tumor microenvironment (TME) and the immune response. At present, several strategies aiming at targeting O-GlcNAcylation are under mostly preclinical evaluation, where the newly developed O-GlcNAcylation inhibitors markedly enhance therapeutic efficacy. Here we systematically outline the mechanisms through which O-GlcNAcylation influences therapy resistance and deliberate on the prospects and challenges associated with targeting O-GlcNAcylation in future cancer treatments.
Topics: Humans; Sugars; Drug Resistance, Neoplasm; Epigenesis, Genetic; Protein Processing, Post-Translational; Neoplasms; N-Acetylglucosaminyltransferases; Acetylglucosamine; Tumor Microenvironment
PubMed: 38401884
DOI: 10.1016/j.canlet.2024.216742 -
World Journal of Microbiology &... Feb 2023Glucosamine (GlcN) is a natural amino monosaccharide in which a hydroxyl group of glucose is substituted by an amino group. It belongs to functional amino sugar... (Review)
Review
Glucosamine (GlcN) is a natural amino monosaccharide in which a hydroxyl group of glucose is substituted by an amino group. It belongs to functional amino sugar compounds. In the traditional preparation process, GlcN and GlcNAc are obtained by hydrolyzing the cell wall of shrimp and crab. There are many potential problems with this method, such as geographical and seasonal restrictions on the supply of raw materials, serious environmental pollution and potential allergic reactions. Microbial fermentation has the advantages of mild conditions, low environmental pollution, high production intensity, and product safety. It can effectively solve the problem of shrimp and crab hydrolysis process, attracting many researchers to participate in the research of microbial fermentation production of GlcN. This paper mainly summarizes the research on strain construction method, metabolic pathway design and fermentation condition optimization in microbial fermentation, which has certain guiding significance for the further production, research and production of glucosamine.
Topics: Glucosamine; Acetylglucosamine; Fermentation; Glucose; Metabolic Networks and Pathways
PubMed: 36754899
DOI: 10.1007/s11274-023-03531-5 -
Journal of Agricultural and Food... Oct 2020-acetyl-d-neuraminic acid (NeuAc) has attracted considerable attention because of its wide-ranging applications. The use of cheap carbon sources such as glucose without...
-acetyl-d-neuraminic acid (NeuAc) has attracted considerable attention because of its wide-ranging applications. The use of cheap carbon sources such as glucose without the addition of any precursor in microbial NeuAc production has many advantages. In this study, improved NeuAc production was attained through the optimization of amino sugar metabolism pathway kinetics and reservation of a phosphoenolpyruvate (PEP) pool in . -acylglucosamine 2-epimerase and -acetylneuraminate synthase from different sources and their best combinations were used to obtain optimized enzyme kinetics and expression intensity, which resulted in a significant increase in NeuAc production. Next, after a design was engineered for enabling the PEP metabolic pathway to retain the PEP pool, the production of NeuAc reached 16.7 g/L, which is the highest NeuAc production rate that has been reported from using glucose as the sole carbon source.
Topics: Amino Sugars; Escherichia coli; Glucose; Metabolic Engineering; Metabolic Networks and Pathways; N-Acetylneuraminic Acid; Phosphoenolpyruvate
PubMed: 32960055
DOI: 10.1021/acs.jafc.0c04725 -
Frontiers in Immunology 2019The human mononuclear phagocytes system consists of dendritic cells (DCs), monocytes, and macrophages having different functions in bridging innate and adaptive... (Review)
Review
The human mononuclear phagocytes system consists of dendritic cells (DCs), monocytes, and macrophages having different functions in bridging innate and adaptive immunity. Among the heterogeneous population of monocytes the cell surface marker slan (6-sulfo LacNAc) identifies a specific subset of human CD14 CD16 non-classical monocytes, called slan monocytes (slanMo). In this review we discuss the identity and functions of slanMo, their contributions to immune surveillance by pro-inflammatory cytokine production, and cross talk with T cells and NK cells. We also consider the role of slanMo in the regulation of chronic inflammatory diseases and cancer. Finally, we highlight unresolved questions that should be the focus of future research.
Topics: Amino Sugars; Humans; Monocytes
PubMed: 31191513
DOI: 10.3389/fimmu.2019.00948 -
Frontiers in Immunology 2019Monocytes are subdivided into three subsets, which have different phenotypic and functional characteristics and different roles in inflammation and malignancy. When in... (Review)
Review
Monocytes are subdivided into three subsets, which have different phenotypic and functional characteristics and different roles in inflammation and malignancy. When in man CD14 and CD16 monoclonal antibodies are used to define these subsets, then the distinction of non-classical CD14low and intermediate CD14high monocytes requires setting a gate in what is a gradually changing level of CD14 expression. In the search for an additional marker to better dissect the two subsets we have explored the marker 6-sulfo LacNAc (slan). Slan is a carbohydrate residue originally described to be expressed on the cell surface of a type of dendritic cell in human blood. We elaborate herein that the features of slan+ cells are congruent with the features of CD16+ non-classical monocytes and that slan is a candidate marker for definition of non-classical monocytes. The use of this marker may help in studying the role of non-classical monocytes in health and in diagnosis and monitoring of disease.
Topics: Amino Sugars; Animals; Biomarkers; Dendritic Cells; Humans; Inflammation; Monocytes; Neoplasms; Phenotype
PubMed: 31572354
DOI: 10.3389/fimmu.2019.02052 -
BioTechniques Feb 2021Five established clearing protocols were compared with a modified and simplified method to determine an optimal clearing reagent for three-dimensionally visualizing...
Five established clearing protocols were compared with a modified and simplified method to determine an optimal clearing reagent for three-dimensionally visualizing fluorophores in the murine liver, a challenging organ to clear. We report successful clearing of whole liver lobes by modification of an established protocol (UbasM) using only Ub-1, a urea-based amino sugar reagent, in a simpler protocol that requires only a 24-h processing time. With Ub-1 alone, we observed sufficiently preserved liver tissue structure in three dimensions along with excellent preservation of fluorophore emissions from endogenous protein reporters and lipophilic tracer dyes. This streamlined technique can be used for 3D cell lineage tracing and fluoroprobe-based reporter gene expression to compare various experimental conditions.
Topics: Amino Sugars; Animals; Fluorescence; Fluorescent Dyes; Liver; Mice; Urea
PubMed: 33467918
DOI: 10.2144/btn-2020-0063 -
European Journal of Medicinal Chemistry Aug 2018Antibiotic resistance has emerged as a serious global public health problem and lately very few antibiotics have been discovered and introduced into clinical practice....
Antibiotic resistance has emerged as a serious global public health problem and lately very few antibiotics have been discovered and introduced into clinical practice. Therefore, there is an urgent need for the development of antibacterial compounds with new mechanism of action, especially those capable of evading known resistance mechanisms. In this work two series of glycoconjugate and non-glycoconjugate amino compounds derived from of isoquinoline-5,8-dione and 1,4-naphthoquinone and their halogenated derivatives were synthesized and evaluated for antimicrobial activity against Gram-positive (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, S. epidermidis ATCC 12228, S. simulans ATCC 27851) and Gram-negative bacteria (E. coli ATCC 25922, Proteus mirabilis ATCC 15290, K. pneumoniae ATCC 4352 and P. aeruginosa ATCC 27853) strains of clinical importance. This study revealed that glycoconjugate compounds derived from halogeno-substituted naphthoquinones were more active against Gram-negative strains, which cause infections whose treatment is even more difficult, according to the literature. These molecules were also more active than isoquinoline-5,8-dione analogues with minimum inhibitory concentration (MIC = 4-32 μg/mL) within Clinical and Laboratory Standard Institute MIC values (CLSI 0.08-256 μg/mL). Interestingly the minimal bactericidal concentration (MBC) values of the most active compounds were equal to MIC classifying them as bactericidal agents against Gram-negative bacteria. Sixteen compounds among eighteen carbohydrate-based naphthoquinones tested showed no hemolytic effects on health human erythrocytes whereas more susceptibility to hemolytic cleavage was observed when using non-glycoconjugate amino compounds. In silico Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) evaluation also pointed out that these compounds are potential for oral administration with low side effects. In general, this study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials more effective against Gram-negative bacteria.
Topics: Amino Sugars; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Halogenation; Hemolysis; Humans; Isoquinolines; Naphthoquinones
PubMed: 30006155
DOI: 10.1016/j.ejmech.2018.06.050 -
Journal of Pharmaceutical and... Feb 2020Erythropoiesis stimulating agents (ESAs) are a group of therapeutic glycoproteins used to treat anaemia caused by chronic kidney disease or chemotherapy. A variety of...
Erythropoiesis stimulating agents (ESAs) are a group of therapeutic glycoproteins used to treat anaemia caused by chronic kidney disease or chemotherapy. A variety of ESA products are available in the European Union, including innovator, biosimilar and second-generation medicines. Glycosylation is a critical quality attribute of ESA products, as it has a crucial influence upon in vivo biological activity. In this study, a combination of chromatography and mass spectrometry analysis has been used to characterise and compare the glycosylation profiles of five ESA products; Eprex® (epoetin alfa), NeoRecormon® (epoetin beta), Binocrit® (epoetin alfa biosimilar), Silapo (epoetin alfa biosimilar) and Aranesp® (darbepoetin alfa). The methods utilised include mixed-mode anion-exchange/hydrophilic interaction chromatography (AEX/HILIC-MS) for N-glycan identification and quantitation, and HILIC-MS for O-glycan characterisation. The products exhibit notable differences in N- and O-glycosylation, including attributes such as sialic acid occupation, O-acetylation, N-acetyllactosamine extended antennae and sulphated/penta-sialylated N-glycans, which have the potential to cause divergence of therapeutic potencies. The study highlights the need for continued monitoring of ESA product glycosylation, ideally allied to pharmacological data, in order to ensure consistency and therapeutic equivalence between products and enhance our understanding of ESA structure-activity-relationships.
Topics: Acetylation; Amino Sugars; Biosensing Techniques; Chromatography, High Pressure Liquid; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Glycosylation; Hematinics; Molecular Structure; N-Acetylneuraminic Acid; Polysaccharides; Recombinant Proteins; Tandem Mass Spectrometry
PubMed: 31838284
DOI: 10.1016/j.jpba.2019.113031 -
Environmental Science and Pollution... Jul 2019Amino sugars (AS) are routinely used as microbial biomarkers to investigate the dynamics of soil carbon (C) and nitrogen (N) under different environments. However, the...
Amino sugars (AS) are routinely used as microbial biomarkers to investigate the dynamics of soil carbon (C) and nitrogen (N) under different environments. However, the effect of any AS on soil C and N, or other AS, is not well-defined. In this study, acid soils from Dongbei (D) and Fujian (F) and alkaline soil from Henan (H) were selected to perform an incubation experiment under glucosamine addition for 36 days. In the present study, the dynamics of soil soluble organic C (SOC), NH-N, NO-N, soluble organic N (SON), and four AS: glucosamine (GluN), mannosamine (ManN), galactosamine (GalN), and muramic acid (MurN), were investigated. The results showed that AS was different among the three soils, but had similar dynamics in the same soil. The higher total C and inorganic N in the D and F relative to the H soil were related to the greater AS in two soils. With incubation, AS decreased in D soil and increased in F soil before 1 week, while after 1 week, the inverse dynamics were observed, which suggest that SOC or SOC combined with inorganic N may be a mechanism to adjust the dynamics of C from AS. Overall, glucosamine addition did not significantly affect AS in D, while the reverse was true for F and H soils. Glucosamine addition decreased AS at day 0 for D soil and at day 3 for F and H soils, and increased SOC. The lowered NH-N and AS in D soil, but the higher values of these, were observed in F soil after 1 week of incubation. The increase of SON in D soil with glucosamine addition might be due to the depolymerization of soil organic matter (SOM) into SON. However, the decrease of SON in F soil could be attributed to the mineralization of SON.
Topics: Amino Sugars; Carbon; Environmental Biomarkers; Forests; Glucosamine; Hydrogen-Ion Concentration; Nitrogen; Soil; Soil Microbiology
PubMed: 31098915
DOI: 10.1007/s11356-019-05353-1