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Carbohydrates fulfil many common as well as extremely important functions in nature. They show a variety of molecular displays - e.g., free mono-, oligo-, and polysaccharides, glycolipids, proteoglycans, glycoproteins, etc. - with particular roles and localizations in living organisms. Structure-specific peculiarities are so many and diverse that i...
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Context 1
... As shown above, the effects of altered oligosaccha- rides on glycoconjugate functions are highly variable and quite unpredictable, and the resulting aberrant glycome composition is oen associated with specic diseases. As an illustration, Table 2 summarizes the diversity of pathological states in which altered glycosylation has been implicated. ...
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Aims/introduction:
Mannose is a monosaccharide constituent of glycoproteins and glycolipids. Experiments in rats have shown previously that the plasma mannose level decreases after glucose load but does not decrease in diabetic rats and that hepatic glycogenolysis is a source of this plasma mannose; however these results are not fully elucidated i...
Citations
... Lectins are used for various biomedical and agricultural applications due to their biotechnological potential and the increasingly detailed investigation of the binding speci city of their particular ligands [1,15,16]. Global glycosylation patterns are heterogeneous between glycoconjugates, cells, tissues, or body uids, and at the same time are dependent on physiological conditions which allow the comparison of glycomic pro les in biological samples from patients under pathological and healthy states [15,17]. Current diagnosis platforms that include several plant lectins with different speci cities (e.g., lectin histochemistry, lectin blotting, lectin microarrays) have become valuable tools allowing the detection of glycosylation alterations and the determination of new glycotope biomarkers of healthy or pathological conditions [4,15,[17][18][19][20][21][22][23][24][25][26][27][28]. ...
... Global glycosylation patterns are heterogeneous between glycoconjugates, cells, tissues, or body uids, and at the same time are dependent on physiological conditions which allow the comparison of glycomic pro les in biological samples from patients under pathological and healthy states [15,17]. Current diagnosis platforms that include several plant lectins with different speci cities (e.g., lectin histochemistry, lectin blotting, lectin microarrays) have become valuable tools allowing the detection of glycosylation alterations and the determination of new glycotope biomarkers of healthy or pathological conditions [4,15,[17][18][19][20][21][22][23][24][25][26][27][28]. ...
Galactia lindenii lectin type-II (GLL-II) belongs to the group of the legume lectins. The present study investigated the GLL-II staining patterns in histological sections of neoplastic and non-neoplastic thyroid tissues. Besides, hemagglutination assays (HA) using the GLL-II on red blood cells (RBCs) of different glycomic profile were performed, complementing previous results. The differential staining in Papillary Thyroid Cancer (PTC), Invasive Encapsulated Follicular Variant Papillary Thyroid Carcinoma (IEFV-PTC), Hashimoto's thyroiditis (HT), and non-neoplastic thyroid with goiter changes, together with the HA results and along with reviewed glycoprofiles of unhealthy conditions in other organs, allowed us to propose the potential utility of GLL-II in lectin platforms used to discriminate human pathological samples from normal ones. The present study shed light on potential applications of GLL-II in determining alterations of glycosylation patterns in specific cells, tissues, or body fluids, as well as glycotopes biomarkers of healthy or pathological conditions.
... In particular, the directed immobilization of complex carbohydrates as found in mammalian systems may be of great interest. Most of those glycans are immobilized on either antibodies or cell surfaces, which restrict their conformation and facilitate specific antibody-antigen interactions (36). Alternative chemical methods to site-specifically functionalize carbohydrates for immobilization on surfaces are time-consuming and involve tedious protection/deprotection steps of hydroxy groups (37,38), thus the use of Shoda's reagent is a promising and simple alternative. ...
The production of biofuels from lignocellulosic biomass using carbohydrate-active enzymes like cellulases is key to sustainable energy production. Understanding the adsorption mechanism of cellulases and associated binding domain proteins down to the molecular level details will help in the rational design of improved cellulases. In nature, carbohydrate-binding modules (CBMs) from families 17 and 28 often appear in tandem appended to the C-terminus of several endocellulases. Both CBMs are known to bind to the amorphous regions of cellulose non-competitively and show similar binding affinity towards soluble cello-oligosaccharides. Based on the available crystal structures, these CBMs may display a uni-directional binding preference towards cello-oligosaccharides (based on how the oligosaccharide was bound within the CBM binding cleft). However, molecular dynamics (MD) simulations have indicated no such clear preference. Considering that most soluble oligosaccharides are not always an ideal substrate surrogate to study the binding of CBMs to the native cell wall or cell surface displayed glycans, it is critical to use alternative reagents or substrates. To experimentally assess any binding directionality of CBMs towards soluble cello-oligosaccharides, we have developed a simple solid-state depletion or pull-down binding assay. Here, we specifically orient azido-labeled carbohydrates from the reducing end to alkyne-labeled micron-sized bead surfaces, using click chemistry, to mimic insoluble cell wall surface-displayed glycans. Our results reveal that both family 17 and 28 CBMs displayed a similar binding affinity towards cellohexaose-modified beads, but not cellopentaose-modified beads, which helps rationalize previously reported crystal structure and MD data. This indicates a preferred uni-directional binding of specific CBMs and could explain their co-evolution as tandem constructs appended to endocellulases to increase amorphous cellulose substrate targeting efficiency. Overall, our proposed workflow can be easily translated to measure the affinity of glycan-binding proteins to click-chemistry based immobilized surface-displayed carbohydrates or antigens.
... Both eukaryotic and prokaryotic cells synthesize glycoconjugates, including glycoproteins, GPI-anchored glycoproteins, proteoglycans, and glycosphingolipids [25]. Glycoproteins are the main class of glycoconjugates [26] and consist of polypeptides that have glycans covalently linked to asparagine and serine/threonine residues (N-glycans and Oglycans, respectively) and through C-mannosylation, where a covalent bond between carbon one of the mannose and carbon two of the indole ring of tryptophan is formed [5]. ...
... GPIs are glycolipids with a conserved core structure of phosphatidylinositol-lipid linked to no-acetylated N-acetyl glucosamine and three mannose residues followed by an ethanolamine [27]. Generally, GPIs have the function of anchoring proteins on the cell membrane in eukaryotes and archaea; additionally, non-protein (linked free GPIs) are abundant on the surface of several protozoan parasites, such as Trypanosoma brucei, Plasmodium falciparum, and Toxoplasma gondii [5]. In addition, GPI-anchored proteins participate in cell signaling and adhesion and are related to health and disease processes [28]. ...
... The chemical diversity and structural complexity of glycans imply that they have diverse biological functions [5]. For example, glycans participate in cell-cell adhesion and cell signaling, provide specific receptors for microorganisms, toxins, or antibodies, and modulate protein functions in a glycosylation-dependent manner [7]. ...
Glycan-based electrochemical biosensors are emerging as analytical tools for determining multiple molecular targets relevant to diagnosing infectious diseases and detecting cancer biomarkers. These biosensors allow for the detection of target analytes at ultra-low concentrations, which is mandatory for early disease diagnosis. Nanostructure-decorated platforms have been demonstrated to enhance the analytical performance of electrochemical biosensors. In addition, glycans anchored to electrode platforms as bioreceptors exhibit high specificity toward biomarker detection. Both attributes offer a synergy that allows ultrasensitive detection of molecular targets of clinical interest. In this context, we review recent advances in electrochemical glycobiosensors for detecting infectious diseases and cancer biomarkers focused on colorectal cancer. We also describe general aspects of structural glycobiology, definitions, and classification of electrochemical biosensors and discuss relevant works on electrochemical glycobiosensors in the last ten years. Finally, we summarize the advances in electrochemical glycobiosensors and comment on some challenges and limitations needed to advance toward real clinical applications of these devices.
... N-glycosylation is highly conserved, while O-glycosylation is less straightforward and greatly differs between various organisms of different kingdoms. The processes of N-and Oglycosylation have been proven to be present in plants [7,44,53], algae and diatoms [54,55], animals [46,[56][57][58], fungi [59,60], bacteria [61,62], Archaea [63] and viruses [64]. In the following paragraphs, only the hallmarks of the processes of N-and O-glycosylation in plants are briefly highlighted. ...
Plant development represents a continuous process in which the plant undergoes morphological, (epi)genetic and metabolic changes. Starting from pollination, seed maturation and germination, the plant continues to grow and develops specialized organs to survive, thrive and generate offspring. The development of plants and the interplay with its environment are highly linked to glycosylation of proteins and lipids as well as metabolism and signaling of sugars. Although the involvement of these protein modifications and sugars is well-studied, there is still a long road ahead to profoundly comprehend their nature, significance, importance for plant development and the interplay with stress responses. This review, approached from the plants’ perspective, aims to focus on some key findings highlighting the importance of glycosylation and sugar signaling for plant development.
... What is not often considered is the viral glycosylation state. The glycosylation state is the assemblage of glycans, linkages of sugars found on the surface of about half of all proteins (13). Influenza contains N-linked glycosylation sites, defined by the Asn-X-Ser/Thr sequon, where X can be anything besides proline (14). ...
Influenza neuraminidase is an important drug target. Glycans are present on neuraminidase, and are generally considered to inhibit antibody binding via their glycan shield. In this work we studied the effect of glycans on the binding kinetics of antiviral drugs to the influenza neuraminidase. We created all-atom in silico systems of influenza neuraminidase with experimentally-derived glycoprofiles consisting of four systems with different glycan conformations and one system without glycans. Using Brownian dynamics simulations, we observe a two- to eight-fold decrease in the rate of ligand binding to the primary binding site of neuraminidase due to the presence of glycans. These glycans are capable of covering much of the surface area of neuraminidase, and the ligand binding inhibition is derived from glycans sterically occluding the primary binding site on a neighboring monomer. Our work also indicates that drugs preferentially bind to the primary binding site (i.e. the active site) over the secondary binding site, and we propose a binding mechanism illustrating this. These results help illuminate the complex interplay between glycans and ligand binding on the influenza membrane protein neuraminidase.
Statement of Significance
Influenza neuraminidase is the target for three FDA-approved influenza drugs in the US. However, drug resistance and low drug effectiveness merits further drug development towards neuraminidase. Generally, drug developers do not include glycans in their development pipelines; we show that glycans can affect drug binding to neuraminidase and thus should be considered when designing new drugs towards influenza, and towards glycoproteins in general.
... Glycans are known to have many important biological functions such as cell-cell, macromolecular (e.g. antibody) and pathogen interactions, protein secretion, protein signaling and protein folding (3,5). ...
Congenital disorders of glycosylation (CDG) form a group of inherited disorders due to glycosylation defects of protein or lipids. The diagnosis of CDG remains a challenge due to a highly varying degree of severity and highly varying clinical manifestations, combined with a high biochemical heterogeneity. To date, more than 125 CDG-causing genes have been identified with a majority that affects the N-linked glycan (N-glycans) synthetics pathway. Hence, glycomics analysis of N-glycans by mass spectrometry (MS) could play an important role to identify novel glycan biomarkers (glycomarkers) for diagnostics and therapy monitoring. In this thesis, we have shown the relevance of glycomics by MS to improve CDG patient care by identification of novel glycomarkers for diagnostics and glycan-indices for therapeutic monitoring of CDG.
... binding of antibodies to their receptors), and pathogen invasion (e.g. toxin binding, virus attachment; see Figure 1) (Defaus et al. 2014). Glycans can also modulate protein function like signaling and influence the half-life of cell surface receptors (e.g. via multivalent lectin-glycan complexes) (Varki 2017). ...
Glycans have important functions in many biological processes such as the interaction of cells with their extracellular environment to mediate cell adhesion, macromolecular interactions, and pathogen invasion. Glycomics comprises the analyses of glycans, released from proteins and/or lipids in any biological sample and is complementary to genomics, metabolomics and proteomics. This chapter highlights developments in glycobiomarker analysis as exemplified by two well-studied groups of disorders, the monogenic congenital disorders of glycosylation (CDG) and cancer. CDGs are a group of genetic defects with abnormal glycosylation of proteins and/or lipids. Protein-specific glycoprofiling has a couple of advantages over the more generally applied total serum glycomics. Glycomics is also a promising approach for personalized medicine in other disease settings and clinical applications beyond cancer and CDG. Protein-specific, high-resolution mass spectrometry of intact serum transferrin has significantly improved CDG diagnostics due to the robustness, speed and accuracy with which glycomarkers for CDG can be obtained for several genetic defects.
... The presented method preserved the outstanding inherent features in the conventional enzyme-linked immunosorbent assay (ELISA) such as sensitivity (36%) and specificity (95%), and also possessed the following benefits: (1) SPR is more time and cost-effective than ELISA, (2) SPR sensor chip can be renewed and reprocessed for more than 100 analyses, (3) there is no need to secondary antibody in SPR assay. In addition, SPR sensor showed the similar sensitivity (36%) and specificity (95%) to ELISA [83,89,90]. ...
Background
Multiple Sclerosis (MS) involves an immune-mediated response in which body’s immune system destructs the protective sheath (myelin). Part of the known MS biomarkers are discovered in cerebrospinal fluid like oligoclonal lgG (OCGB), and also in blood like myelin Oligodendrocyte Glycoprotein (MOG). The conventional MS diagnostic methods often fail to detect the disease in early stages such as Clinically Isolated Syndrome (CIS), which considered as a concerning issue since CIS highlighted as a prognostic factor of MS development in most cases.
Methods
MS diagnostic techniques include Magnetic Resonance Imaging (MRI) of the brain and spinal cord, lumbar puncture (or spinal tap) that evaluate cerebrospinal fluid, evoked potential testing revealing abnormalities in the brain and spinal cord. These conventional diagnostic methods have some negative points such as extensive processing time as well as restriction in the quantity of samples that can be analyzed concurrently. Scientists have focused on developing the detection methods especially early detection which belongs to ultra-sensitive, non-invasive and needed for the Point of Care (POC) diagnosis because the situation was complicated by false positive or negative results.
Results
As a result, biosensors are utilized and investigated since they could be ultra-sensitive to specific compounds, cost effective devices, body-friendly and easy to implement. In addition, it has been proved that the biosensors on physiological fluids (blood, serum, urine, saliva, milk etc.) have quick response in a non-invasive rout. In general form, a biosensor system for diagnosis and early detection process usually involves; biomarker (target molecule), bio receptor (recognition element) and compatible bio transducer.
Conclusion
Studies underlined that early treatment of patients with high possibility of MS can be advantageous by postponing further abnormalities on MRI and subsequent attacks.
This Review highlights variable disease diagnosis approaches such as Surface Plasmon Resonance (SPR), electrochemical biosensors, Microarrays and microbeads based Microarrays, which are considered as promising methods for detection and early detection of MS.
... Therefore, glycan structures are highly diverse, with multiple possibilities for branching and linkage (micro-heterogeneity) and differences in site occupancy (macro-heterogeneity). Glycans are known to have many important biological functions, such as cell-cell, macromolecular (e.g., antibody) and pathogen interactions, protein secretion, protein signaling, and protein folding (Moremen et al 2012;Defaus et al 2014). ...
Clinical glycomics comprises a spectrum of different analytical methodologies to analyze glycan structures, which provides insights into the mechanisms of glycosylation. Within clinical diagnostics, glycomics serves as a functional readout of genetic variants, and can form a basis for therapy development, as was described for PGM1-CDG. Integration of glycomics with genomics has resulted in the elucidation of previously unknown disorders of glycosylation, namely CCDC115-CDG, TMEM199-CDG, ATP6AP1-CDG, MAN1B1-CDG, and PGM1-CDG. This review provides an introduction into protein glycosylation and presents the different glycomics methodologies ranging from gel electrophoresis to mass spectrometry (MS) and from free glycans to intact glycoproteins. The role of glycomics in the diagnosis of congenital disorders of glycosylation (CDG) is presented, including a diagnostic flow chart and an overview of glycomics data of known CDG subtypes. The review ends with some future perspectives, showing upcoming technologies as system wide mapping of the N- and O-glycoproteome, intact glycoprotein profiling and analysis of sugar metabolism. These new advances will provide additional insights and opportunities to develop personalized therapy. This is especially true for inborn errors of metabolism, which are amenable to causal therapy, because interventions through supplementation therapy can directly target the pathogenesis at the molecular level.
... While the mechanisms underlying autophagy activation in B6ras cells are undefined, in immortalized Jurkat T lymphocytes and T cells derived from mice and human donors, BNIP3 expression and mitochondrial localization is induced by CD47 activation [171]. While the use of Tsp1 peptides suggests that glycosylation is dispensable for autophagy activation, Tsp1 glycosylation would be needed for the extracellular transit of the full-length glycoprotein [53,172,173] and there is evidence that receptor GAGs mediate Tsp1 binding in T cells [174]. Given the diverse interactome of Tsp1 [175] and the reported CD47-independent activities of the Tsp1 (4NIK) peptide [176], knockdown experiments targeting Tsp1 binding partners should be utilized in validating the how exogenous Tsp1 regulates autophagy. ...
Glycoconjugates, glycans, carbohydrates, and sugars: these terms encompass a class of biomolecules that are diverse in both form and function ranging from free oligosaccharides, glycoproteins, and proteoglycans, to glycolipids that make up a complex glycan code that impacts normal physiology and disease. Recent data suggest that one mechanism by which glycoconjugates impact physiology is through the regulation of the process of autophagy. Autophagy is a degradative pathway necessary for differentiation, organism development, and the maintenance of cell and tissue homeostasis. In this review, we will highlight what is known about the regulation of autophagy by glycoconjugates focusing on signaling mechanisms from the extracellular surface and the regulatory roles of intracellular glycans. Glycan signaling from the extracellular matrix converges on “master” regulators of autophagy including AMPK and mTORC1, thus impacting their localization, activity, and/or expression. Within the intracellular milieu, gangliosides are constituents of the autophagosome membrane, a subset of proteins composing the autophagic machinery are regulated by glycosylation, and oligosaccharide exposure in the cytosol triggers an autophagic response. The examples discussed provide some mechanistic insights into glycan regulation of autophagy and reveal areas for future investigation.
