Fucosylation

NOTCH1 (N1) is a transmembrane receptor interacting with membrane-tethered ligands on opposing cells that mediate the direct cell-cell interaction necessary for many cell fate decisions. Protein O -fucosyltransferase 1 (POFUT1) adds O -fucose to Epidermal Growth Factor (EGF)-like repeats in the NOTCH1 extracellular domain, which is required for trafficking and signaling activation. We previously showed that POFUT1 S162L caused a 90% loss of POFUT1 activity and global developmental defects in a patient; however, the mechanism by which POFUT1 contributes to these symptoms is still unclear...

Glycosylation of cancerous epithelial MUC1 protein is specifically altered in comparison to that which is presented by healthy cells. One of such changes is appearing tumor-associated carbohydrate antigens (TACAs) which are rare in normal tissues and are highly correlated with poor clinical outcomes and cancer progression. This review summarizes and describes the role of Tn, T antigens, their sialylated forms as well as fucosylated Lewis epitopes in different aspects of tumor development, progression, and metastasis...

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide COVID-19 pandemic, leading to 6.8 million deaths. Numerous variants have emerged since its outbreak, resulting in its significantly enhanced ability to spread among humans. As with many other viruses, SARS‑CoV‑2 utilizes heparan sulfate (HS) glycosaminoglycan (GAG) on the surface of host cells to facilitate viral attachment and initiate cellular entry through the ACE2 receptor. Therefore, interfering with virion-HS interactions represents a promising target to develop broad-spectrum antiviral therapeutics...

Glycosylation alterations in TNBC have significant implications for tumor behavior, diagnosis, prognosis, and therapeutic strategies. Dysregulated glycosylation affects cell adhesion, signaling, immune recognition, and response to therapy in TNBC. Different types of glycosylation, including N-linked glycosylation, O-linked glycosylation, glycosphingolipid glycosylation, mucin-type glycosylation, and sialylation, play distinct roles in TNBC. The "barcoding" method based on glycosylation sites of the membrane type mannose receptor (MR) shows promise in accurately distinguishing breast cancer subtypes, including TNBC...

The majority of bioactive polysaccharides are present in some marine creatures. These polysaccharides are considered as promising anti-obesity agents, their anti-obesity properties involve a number of mechanisms, including suppression of lipid metabolism and absorption, impact on satiety, and prevention of adipocyte differentiation. Obesity is linked to type 2 diabetes, cardiovascular disease, and other metabolic syndromes. In this review various bioactive polysaccharides like chitin, chitosan, fucosylated chondroitin sulphate, chitooligosaccharides and glycosaminoglycans have been discussed for their anti-obesity effects through various pathways...

Down syndrome (DS) is characterized by lowered immune competence and premature aging. We previously showed decreased antibody response following SARS-CoV-2 vaccination in adults with DS. IgG1 Fc glycosylation patterns are known to affect the effector function of IgG and are associated with aging. Here, we compare total and anti-spike (S) IgG1 glycosylation patterns following SARS-CoV-2 vaccination in DS and healthy controls (HC). Total and anti-Spike IgG1 Fc N-glycan glycoprofiles were measured in non-exposed adults with DS and controls before and after SARS-CoV-2 vaccination by liquid chromatography-mass spectrometry (LC-MS) of Fc glycopeptides...

Mapping the N-glycome of porcine sperm before and after sperm capacitation is important for understanding the rearrangement of glycoconjugates during capacitation. In this work, we characterized the N-glycome on the membranes of 18 pairs of fresh porcine sperm before capacitation and porcine sperm after capacitation by MALDI-MS (Matrix-assisted laser desorption/ionization-mass spectrometry). A total of 377 N-glycans were detected and a comprehensive N-glycome map of porcine sperm membranes before and after capacitation was generated, which presents the largest N-glycome dataset of porcine sperm cell membranes...

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There is an urgent need for new high-quality markers for the early detection of hepatocellular carcinoma (HCC). Åström et al. suggested that S2-bound α1-acid glycoprotein (AGP) might be a promising marker. Consequently, we evaluated the predictive advantage of S2-bound AGP in the early detection of HCC. In a retrospective case-control study of patients chronically infected with hepatitis C virus (HCV) and treated with direct-acting antiviral agents (n = 93), we measured S2-bound AGP using the HepaCheC® ELISA kit (Glycobond AB, Linköping, SE) at the start of treatment, end of treatment and follow-up (maximum: 78 months)...

For acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA) is well established. However, the narrow application and tolerance development of ATRA remain to be improved. In this study, we investigated the effects of combinations of glycosylation inhibitors with ATRA to achieve better efficiency than ATRA alone. We found that the combination of fucosylation inhibitor 6-alkynylfucose (6AF) and ATRA had an additional effect on cell differentiation, as revealed by expression changes in two differentiation markers, CD11b and CD11c, and significant morphological changes in NB4 APL and HL-60 acute myeloid leukemia (AML) cells...

Mesenchymal stem/stromal cells (MSCs) are being increasingly used in cell-based therapies due to their broad anti-inflammatory and immunomodulatory properties. Intravascularly-administered MSCs do not efficiently migrate to sites of inflammation/immunopathology, but this shortfall has been overcome by cell surface enzymatic fucosylation to engender expression of the potent E-selectin ligand HCELL. In applications of cell-based therapies, cryopreservation enables stability in both storage and transport of the produced cells from the manufacturing facility to the point of care...

Fucosylation is facilitated by converting GDP-mannose to GDP-4-keto-6-deoxymannose, which GDP-mannose 4,6-dehydratase, a crucial enzyme in the route, carries out. One of the most prevalent glycosylation alterations linked to cancer has reportedly been identified as fucosylation. There is mounting evidence that GMDS is intimately linked to the onset and spread of cancer. Furthermore, the significance of long-chain non-coding RNAs in the development and metastasis of cancer is becoming more well-recognized, and the regulatory mechanism of lncRNAs has emerged as a prominent area of study in the biological sciences...

Human noroviruses, globally the main cause of viral gastroenteritis, show strain specific affinity for histo-blood group antigens (HBGA) and can successfully be propagated ex vivo in human intestinal enteroids (HIEs). HIEs established from jejunal stem cells of individuals with different ABO, Lewis and secretor geno- and phenotypes, show varying susceptibility to such infections. Using bottom-up glycoproteomic approaches we have defined and compared the N-linked glycans of glycoproteins of seven jejunal HIEs...

Glycans are complex biomolecules that encode rich information and regulate various biological processes, such as fertilization, host-pathogen binding, and immune recognition, through interactions with glycan-binding proteins. A key driving force for glycan-protein recognition is the interaction between the π electron density of aromatic amino acid side chains and polarized C─H groups of the pyranose (termed the CH-π interaction). However, the relatively weak binding affinity between glycans and proteins has hindered the application of glycan detection and imaging...

Biological experiments are often conducted in vitro using immortalized cells due to their accessibility and ease of propagation compared to primary cells and live animals. However, immortalized cells may present different proteomic and glycoproteomic characteristics from the primary cell source due to the introduction of genes that enhance proliferation (e.g. CDK4) or enable telomere lengthening. To demonstrate the changes in phenotype upon CDK4-transformation, we performed LC-MS/MS glycomic and proteomic characterization of a human lung cancer primary cell line (DTW75) and a CDK4-transformed cell line (GL01) derived from DTW75...

Background: Breast milk is the gold standard of infant nutrition, delivering nutrients and bioactive molecules as needed to support optimal infant growth and cognitive development. Increasing evidence links human milk oligosaccharides (HMOs) to these early childhood development milestones. Aims: To summarize and synthesize the evidence relating to HMOs and infant brain development, physical growth, and cognitive development. In addition, HMO concentrations in secretor and nonsecretor mothers were compared via a meta-analysis...

Cell membrane glycoproteins are generally highly fucosylated and sialylated, and post-translational modifications play important roles in the proteins' functions of signaling, binding and cellular processing. For these reasons, methods for measuring sialic acid-mediated protein-protein interactions have been developed. However, determining the role of fucose in these interactions has been limited by technological barriers that have thus far hindered the ability to characterize and observe fucose-mediated protein-protein interactions...

Millions of tons of citrus peel waste are produced every year as a byproduct of the juice industry. Citrus peel is rich in pectin and xyloglucan, but while the pectin is extracted for use in the food industry, the xyloglucan is currently not valorized. To target hydrolytic degradation of citrus peel xyloglucan into oligosaccharides, we have used bioinformatics to identify three glycoside hydrolase 12 (GH12) endoxyloglucanases (EC 3.2.1.151) from the citrus fruit pathogens Penicillium italicum GL-Gan1 and Penicillium digitatum Pd1 and characterized them on xyloglucan obtained by alkaline extraction from citrus peel...

Fucosylation is an important structural feature of glycans and plays an essential role in the regulation of glycoprotein functions. Fucosylation can be classified into core- (CF) and antenna-fucosylation (AF, also known as (sialyl-) Lewis) based on the location on N -glycans, and they perform distinct biological functions. In this study, core- and antenna-fucosylated N -glycans on human serum glycoproteins that hold great clinical application values were systematically characterized at the site-specific level using StrucGP combined with the recently developed fucosylation assignment method...

INTRODUCTION: Hypoxic-ischemic encephalopathy (HIE) is one of severe neonatal brain injuries, resulting from inflammation and the immune response after perinatal hypoxia and ischemia. IgG N-glycosylation plays a crucial role in various inflammatory diseases through mediating the balance between anti-inflammatory and pro-inflammatory responses. This study aimed to explore the effect of IgG N-glycosylation on the development of HIE. METHODS: This case-control study included 53 HIE patients and 57 control neonates...