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International Journal of Molecular... Oct 2020The so-called "" has become an attractive research area, as an increasing number of natural products containing a sialic acid moiety have been shown to play important... (Review)
Review
The so-called "" has become an attractive research area, as an increasing number of natural products containing a sialic acid moiety have been shown to play important roles in biological, pathological, and immunological processes. The intramolecular lactones of sialic acids are a subclass from this crucial family that could have central functions in the discrimination of physiological and pathological conditions. In this review, we report an in-depth analysis of the synthetic achievements in the preparation of the intramolecular lactones of sialic acids (1,4-, 1,7- and γ-lactones), in their free and/or protected form. In particular, recent advances in the synthesis of the 1,7-lactones have allowed the preparation of key sialic acid derivatives. These compounds could be used as authentic reference standards for their correct determination in biological samples, thus overcoming some of the limitations of the previous analytical procedures.
Topics: Lactones; Sialic Acids
PubMed: 33143039
DOI: 10.3390/ijms21218098 -
Glycobiology Oct 2022N-glycolylated carbohydrates are amino sugars with an N-glycolyl amide group. These glycans have not been well studied due to their surprising rarity in nature in... (Review)
Review
N-glycolylated carbohydrates are amino sugars with an N-glycolyl amide group. These glycans have not been well studied due to their surprising rarity in nature in comparison with N-acetylated carbohydrates. Recently, however, there has been increasing interest in N-glycolylated sugars because the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc), apparently the only source of all N-glycolylated sugars in deuterostomes, appears to be involved in xenosialitis (inflammation associated with consumption of Neu5Gc-rich red meats). Xenosialitis has been implicated in cancers as well as other diseases including atherosclerosis. Furthermore, metabolites of Neu5Gc have been shown to be incorporated into glycosaminoglycans (GAGs), resulting in N-glycolylated GAGs. These N-glycolylated GAGs have important potential applications, such as dating the loss of the Neu5Gc-generating CMAH gene in humans and being explored as a xenosialitis biomarker and/or estimate of the body burden of diet-derived Neu5Gc, to understand the risks associated with the consumption of red meats. This review explores N-glycolylated carbohydrates, how they are metabolized to N-glycolylglucosamine and N-glycolylgalactosamine, and how these metabolites can be incorporated into N-glycolylated GAGs in human tissues. We also discuss other sources of N-glycolylated sugars, such as recombinant production from microorganisms using metabolic engineering as well as chemical synthesis.
Topics: Humans; Neuraminic Acids; N-Acetylneuraminic Acid; Amino Sugars; Polysaccharides; Inflammation
PubMed: 35925816
DOI: 10.1093/glycob/cwac048 -
Cells Nov 2022The modification of nuclear, mitochondrial, and cytosolic proteins by O-linked βN-acetylglucosamine (O-GlcNAc) has emerged as a dynamic and essential post-translational... (Review)
Review
The modification of nuclear, mitochondrial, and cytosolic proteins by O-linked βN-acetylglucosamine (O-GlcNAc) has emerged as a dynamic and essential post-translational modification of mammalian proteins. O-GlcNAc is cycled on and off over 5000 proteins in response to diverse stimuli impacting protein function and, in turn, epigenetics and transcription, translation and proteostasis, metabolism, cell structure, and signal transduction. Environmental and physiological injury lead to complex changes in O-GlcNAcylation that impact cell and tissue survival in models of heat shock, osmotic stress, oxidative stress, and hypoxia/reoxygenation injury, as well as ischemic reperfusion injury. Numerous mechanisms that appear to underpin O-GlcNAc-mediated survival include changes in chaperone levels, impacts on the unfolded protein response and integrated stress response, improvements in mitochondrial function, and reduced protein aggregation. Here, we discuss the points at which O-GlcNAc is integrated into the cellular stress response, focusing on the roles it plays in the cardiovascular system and in neurodegeneration.
Topics: Animals; Acetylglucosamine; Protein Processing, Post-Translational; Glycosylation; Oxidative Stress; Signal Transduction; Proteins; Mammals
PubMed: 36359905
DOI: 10.3390/cells11213509 -
Molecules (Basel, Switzerland) Feb 2023Microbial production of hyaluronic acid (HA) is an area of research that has been gaining attention in recent years due to the increasing demand for this biopolymer for... (Review)
Review
Microbial production of hyaluronic acid (HA) is an area of research that has been gaining attention in recent years due to the increasing demand for this biopolymer for several industrial applications. Hyaluronic acid is a linear, non-sulfated glycosaminoglycan that is widely distributed in nature and is mainly composed of repeating units of N-acetylglucosamine and glucuronic acid. It has a wide and unique range of properties such as viscoelasticity, lubrication, and hydration, which makes it an attractive material for several industrial applications such as cosmetics, pharmaceuticals, and medical devices. This review presents and discusses the available fermentation strategies to produce hyaluronic acid.
Topics: Hyaluronic Acid; Fermentation; Chemical Phenomena; Acetylglucosamine; Glucuronic Acid
PubMed: 36903332
DOI: 10.3390/molecules28052084 -
Parasitology Dec 2019Many invertebrates are either parasites themselves or vectors involved in parasite transmission; thereby, the interactions of parasites with final or intermediate hosts... (Comparative Study)
Comparative Study Review
Many invertebrates are either parasites themselves or vectors involved in parasite transmission; thereby, the interactions of parasites with final or intermediate hosts are often mediated by glycans. Therefore, it is of interest to compare the glycan structures or motifs present across invertebrate species. While a typical vertebrate modification such as sialic acid is rare in lower animals, antennal and core modifications of N-glycans are highly varied and range from core fucose, galactosylated fucose, fucosylated galactose, methyl groups, glucuronic acid and sulphate through to addition of zwitterionic moieties (phosphorylcholine, phosphoethanolamine and aminoethylphosphonate). Only in some cases are the enzymatic bases and the biological function of these modifications known. We are indeed still in the phase of discovering invertebrate glycomes primarily using mass spectrometry, but molecular biology and microarraying techniques are complementary to the determination of novel glycan structures and their functions.
Topics: Animals; Fucose; Glycosylation; Host-Parasite Interactions; Invertebrates; Polysaccharides; Sialic Acids; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 31046847
DOI: 10.1017/S0031182019000398 -
Bioconjugate Chemistry Apr 2022-Acetyl-β-d-hexosaminidases (EC 3.2.1.52) are exo-acting glycosyl hydrolases that remove -acetyl-β-d-glucosamine (Glc-NAc) or -acetyl-β-d-galactosamine (Gal-NAc) from... (Review)
Review
-Acetyl-β-d-hexosaminidases (EC 3.2.1.52) are exo-acting glycosyl hydrolases that remove -acetyl-β-d-glucosamine (Glc-NAc) or -acetyl-β-d-galactosamine (Gal-NAc) from the nonreducing ends of various biomolecules including oligosaccharides, glycoproteins, and glycolipids. The same enzymes are sometimes called -acetyl-β-d-glucosaminidases, and this review article employs the shorthand descriptor HEX(NAG) to indicate that the terms HEX or NAG are used interchangeably in the literature. The wide distribution of HEX(NAG) throughout the biosphere and its intracellular location in lysosomes combine to make it an important enzyme in food science, agriculture, cell biology, medical diagnostics, and chemotherapy. For more than 50 years, researchers have employed chromogenic derivatives of -acetyl-β-d-glucosaminide in basic assays for biomedical research and clinical chemistry. Recent conceptual and synthetic innovations in molecular fluorescence sensors, along with concurrent technical improvements in instrumentation, have produced a growing number of new fluorescent imaging and diagnostics methods. A systematic summary of the recent advances in optical sensors for HEX(NAG) is provided under the following headings: assessing kidney health, detection and treatment of infectious disease, fluorescence imaging of cancer, treatment of lysosomal disorders, and reactive probes for chemical biology. The article concludes with some comments on likely future directions.
Topics: Acetylglucosaminidase; Glucosamine; Glycolipids; Hydrolases; beta-N-Acetylhexosaminidases
PubMed: 35302753
DOI: 10.1021/acs.bioconjchem.2c00057 -
The Journal of Biological Chemistry Apr 2022Nucleotide sugar (NS) dehydratases play a central role in the biosynthesis of deoxy and amino sugars, which are involved in a variety of biological functions in all... (Review)
Review
Nucleotide sugar (NS) dehydratases play a central role in the biosynthesis of deoxy and amino sugars, which are involved in a variety of biological functions in all domains of life. Bacteria are true masters of deoxy sugar biosynthesis as they can produce a wide range of highly specialized monosaccharides. Indeed, deoxy and amino sugars play important roles in the virulence of gram-positive and gram-negative pathogenic species and are additionally involved in the biosynthesis of diverse macrolide antibiotics. The biosynthesis of deoxy sugars relies on the activity of NS dehydratases, which can be subdivided into three groups based on their structure and reaction mechanism. The best-characterized NS dehydratases are the 4,6-dehydratases that, together with the 5,6-dehydratases, belong to the NS-short-chain dehydrogenase/reductase superfamily. The other two groups are the less abundant 2,3-dehydratases that belong to the Nudix hydrolase superfamily and 3-dehydratases, which are related to aspartame aminotransferases. 4,6-Dehydratases catalyze the first step in all deoxy sugar biosynthesis pathways, converting nucleoside diphosphate hexoses to nucleoside diphosphate-4-keto-6-deoxy hexoses, which in turn are further deoxygenated by the 2,3- and 3-dehydratases to form dideoxy and trideoxy sugars. In this review, we give an overview of the NS dehydratases focusing on the comparison of their structure and reaction mechanisms, thereby highlighting common features, and investigating differences between closely related members of the same superfamilies.
Topics: Hydro-Lyases; Nucleosides; Nucleotides; Substrate Specificity; Sugars
PubMed: 35271853
DOI: 10.1016/j.jbc.2022.101809 -
Cellular Signalling Feb 2022O-GlcNAcylation is a post-translational modification occurring on serine/threonine residues of nuclear and cytoplasmic proteins, mediated by the enzymes OGT and OGA... (Review)
Review
O-GlcNAcylation is a post-translational modification occurring on serine/threonine residues of nuclear and cytoplasmic proteins, mediated by the enzymes OGT and OGA which catalyze the addition or removal of the UDP-GlcNAc moieties, respectively. Structural changes brought by this modification lead to alternations of protein stability, protein-protein interactions, and phosphorylation. Importantly, O-GlcNAcylation is a nutrient sensor by coupling nutrient sensing with cellular signaling. Elevated levels of OGT and O-GlcNAc have been reported in a variety of cancers and has been linked to regulation of multiple cancer signaling pathways. In this review, we discuss the most recent findings on the role of O-GlcNAcylation as a metabolic sensor in signaling pathways and immune response in cancer.
Topics: Acetylglucosamine; Humans; N-Acetylglucosaminyltransferases; Neoplasms; Phosphorylation; Protein Processing, Post-Translational
PubMed: 34800629
DOI: 10.1016/j.cellsig.2021.110201 -
Molecules (Basel, Switzerland) Aug 2019Galactosaminoglycans (GalAGs) are sulfated glycans composed of alternating -acetylgalactosamine and uronic acid units. Uronic acid epimerization, sulfation patterns and... (Review)
Review
Galactosaminoglycans (GalAGs) are sulfated glycans composed of alternating -acetylgalactosamine and uronic acid units. Uronic acid epimerization, sulfation patterns and fucosylation are modifications observed on these molecules. GalAGs have been extensively studied and exploited because of their multiple biomedical functions. Chondroitin sulfates (CSs), the main representative family of GalAGs, have been used in alternative therapy of joint pain/inflammation and osteoarthritis. The relatively novel fucosylated chondroitin sulfate (FCS), commonly found in sea cucumbers, has been screened in multiple systems in addition to its widely studied anticoagulant action. Biomedical properties of GalAGs are directly dependent on the sugar composition, presence or lack of fucose branches, as well as sulfation patterns. Although research interest in GalAGs has increased considerably over the three last decades, perhaps motivated by the parallel progress of glycomics, serious questions concerning the effectiveness and potential side effects of GalAGs have recently been raised. Doubts have centered particularly on the beneficial functions of CS-based therapeutic supplements and the potential harmful effects of FCS as similarly observed for oversulfated chondroitin sulfate, as a contaminant of heparin. Unexpected components were also detected in CS-based pharmaceutical preparations. This review therefore aims to offer a discussion on (1) the current and potential therapeutic applications of GalAGs, including those of unique features extracted from marine sources, and (2) the potential drawbacks of this class of molecules when applied to medicine.
Topics: Acetylgalactosamine; Arthralgia; Chondroitin Sulfates; Humans; Osteoarthritis; Polysaccharides; Uronic Acids
PubMed: 31374852
DOI: 10.3390/molecules24152803 -
Journal of Leukocyte Biology Dec 2022Some extracellular glycoconjugates have sialic acid as the terminal sugar, and sialidases are enzymes that remove this sugar. Mammals have 4 sialidases and can be...
Some extracellular glycoconjugates have sialic acid as the terminal sugar, and sialidases are enzymes that remove this sugar. Mammals have 4 sialidases and can be elevated in inflammation and fibrosis. In this report, we show that incubation of human neutrophils with the extracellular human sialidase NEU3, but not NEU1, NEU2 or NEU4, induces human male and female neutrophils to change from a round to a more amoeboid morphology, causes the primed human neutrophil markers CD11b, CD18, and CD66a to localize to the cell cortex, and decreases the localization of the unprimed human neutrophil markers CD43 and CD62-L at the cell cortex. NEU3, but not the other 3 sialidases, also causes human male and female neutrophils to increase their F-actin content. Human neutrophils treated with NEU3 show a decrease in cortical levels of Sambucus nigra lectin staining and an increase in cortical levels of peanut agglutinin staining, indicating a NEU3-induced desialylation. The inhibition of NEU3 by the NEU3 inhibitor 2-acetylpyridine attenuated the NEU3 effect on neutrophil morphology, indicating that the effect of NEU3 is dependent on its enzymatic activity. Together, these results indicate that NEU3 can prime human male and female neutrophils, and that NEU3 is a potential regulator of inflammation.
Topics: Female; Humans; Male; Inflammation; N-Acetylneuraminic Acid; Neuraminidase; Neutrophils; Sugars
PubMed: 35899930
DOI: 10.1002/JLB.3A0422-217RR